insuficiencia cardíaca fisiopatología · pdf filees potenciada en la...
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Insuficiencia cardiacuteaca
FISIOPATOLOGIacuteA Rafael Porcile
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D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
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LEY DE
STARLING
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HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
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PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
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HIPOPERFUSION
ANTEROGRADA
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MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
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Insuficiencia cardiacuteaca
ACTIVACIOacuteN
ADRENERGICA Rafael Porcile
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D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
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MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
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DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
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Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
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Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
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SISTEMA LIMBICO rafaelporcilevaneduceduar
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BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
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Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
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MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
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NUEVOS ACTORES
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La renina es una enzima
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Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
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Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
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Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
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SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
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La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
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angiotensina (1-7)
Su mecasismo es
PARACRINO
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La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
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La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
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Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
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Angiotensina II
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FUENTES DE
ANGIOTENSINA
II
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ALDOSTERONA
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ALDOSTERONA
ANGIOTENSINA II
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ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
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Proliferacioacuten colaacutegeno
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APOPTOSIS
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FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
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HORMAONA
ANTIDIURETICA
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ADH
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Reduccion de la natremia
ANGIOTENSINA II
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Angiotensina
III y
IV
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En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
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Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
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ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
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HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
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MECANISMOS
COMPENSADORES
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ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
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Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
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Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
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Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
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D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
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ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
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Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
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Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
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Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
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Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
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Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
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Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
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Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
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Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
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LEY DE
STARLING
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HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
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PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
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HIPOPERFUSION
ANTEROGRADA
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MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
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Insuficiencia cardiacuteaca
ACTIVACIOacuteN
ADRENERGICA Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
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MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
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DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
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Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
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Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
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SISTEMA LIMBICO rafaelporcilevaneduceduar
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BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
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Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
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MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
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NUEVOS ACTORES
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La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
LEY DE
STARLING
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
rafaelporcilevaneduceduar
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
rafaelporcilevaneduceduar
HIPOPERFUSION
ANTEROGRADA
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
ACTIVACIOacuteN
ADRENERGICA Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
rafaelporcilevaneduceduar
Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
LEY DE
STARLING
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
rafaelporcilevaneduceduar
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
rafaelporcilevaneduceduar
HIPOPERFUSION
ANTEROGRADA
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
ACTIVACIOacuteN
ADRENERGICA Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
rafaelporcilevaneduceduar
Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
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FUENTES DE
ANGIOTENSINA
II
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rafaelporcilevaneduceduar
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ALDOSTERONA
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ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
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Proliferacioacuten colaacutegeno
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APOPTOSIS
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FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
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HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
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Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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Angiotensina
III y
IV
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En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
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Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
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ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
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HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
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Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
LEY DE
STARLING
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
rafaelporcilevaneduceduar
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
rafaelporcilevaneduceduar
HIPOPERFUSION
ANTEROGRADA
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
ACTIVACIOacuteN
ADRENERGICA Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
rafaelporcilevaneduceduar
Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
LEY DE
STARLING
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
rafaelporcilevaneduceduar
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
rafaelporcilevaneduceduar
HIPOPERFUSION
ANTEROGRADA
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
ACTIVACIOacuteN
ADRENERGICA Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
rafaelporcilevaneduceduar
Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
rafaelporcilevaneduceduar
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
rafaelporcilevaneduceduar
HIPOPERFUSION
ANTEROGRADA
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
ACTIVACIOacuteN
ADRENERGICA Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
rafaelporcilevaneduceduar
Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
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Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
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SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
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La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
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angiotensina (1-7)
Su mecasismo es
PARACRINO
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La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
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La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
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Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
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Angiotensina II
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FUENTES DE
ANGIOTENSINA
II
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ALDOSTERONA
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ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
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Proliferacioacuten colaacutegeno
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APOPTOSIS
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FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
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HORMAONA
ANTIDIURETICA
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ADH
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Reduccion de la natremia
ANGIOTENSINA II
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Angiotensina
III y
IV
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En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
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Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
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ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
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HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
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MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
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Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
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Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
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Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
rafaelporcilevaneduceduar
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
rafaelporcilevaneduceduar
HIPOPERFUSION
ANTEROGRADA
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
ACTIVACIOacuteN
ADRENERGICA Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
rafaelporcilevaneduceduar
Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
rafaelporcilevaneduceduar
HIPOPERFUSION
ANTEROGRADA
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
ACTIVACIOacuteN
ADRENERGICA Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
rafaelporcilevaneduceduar
Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
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Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
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HIPOPERFUSION
ANTEROGRADA
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
ACTIVACIOacuteN
ADRENERGICA Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
rafaelporcilevaneduceduar
Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
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Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
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SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
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La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
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angiotensina (1-7)
Su mecasismo es
PARACRINO
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La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
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La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
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Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
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Angiotensina II
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FUENTES DE
ANGIOTENSINA
II
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ALDOSTERONA
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ALDOSTERONA
ANGIOTENSINA II
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ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
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Proliferacioacuten colaacutegeno
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APOPTOSIS
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FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
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HORMAONA
ANTIDIURETICA
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ADH
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Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
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Angiotensina
III y
IV
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En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
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Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
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ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
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HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
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MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
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Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
ACTIVACIOacuteN
ADRENERGICA Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
rafaelporcilevaneduceduar
Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
ACTIVACIOacuteN
ADRENERGICA Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
rafaelporcilevaneduceduar
Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
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Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
ACTIVACIOacuteN
ADRENERGICA Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
rafaelporcilevaneduceduar
Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
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Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
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SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
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La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
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angiotensina (1-7)
Su mecasismo es
PARACRINO
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La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
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La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
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Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
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Angiotensina II
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FUENTES DE
ANGIOTENSINA
II
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ALDOSTERONA
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ALDOSTERONA
ANGIOTENSINA II
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ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
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Proliferacioacuten colaacutegeno
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APOPTOSIS
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FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
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HORMAONA
ANTIDIURETICA
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ADH
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Reduccion de la natremia
ANGIOTENSINA II
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Angiotensina
III y
IV
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En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
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Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
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ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
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HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
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MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
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Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
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Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
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ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
rafaelporcilevaneduceduar
Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
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DOS MECANISMOS
bull Mecanismo neurogenico
reflejo
bull Mecanismo neuro endorino
rafaelporcilevaneduceduar
Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
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rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
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Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
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La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
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SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
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Mecanismo
neuroigenico reflejo
BULBO Y PROTUBERANCIA
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
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rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
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Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
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NUEVOS ACTORES
rafaelporcilevaneduceduar
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La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
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Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
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SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
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Angiotensina II
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FUENTES DE
ANGIOTENSINA
II
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ALDOSTERONA
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ALDOSTERONA
ANGIOTENSINA II
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ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
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Proliferacioacuten colaacutegeno
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APOPTOSIS
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FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
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HORMAONA
ANTIDIURETICA
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ADH
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Reduccion de la natremia
ANGIOTENSINA II
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Angiotensina
III y
IV
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En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
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Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
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ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
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HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
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MECANISMOS
COMPENSADORES
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ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
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Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
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Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
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Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
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ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
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Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
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Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
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Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Mecanismo neurogenico
INHIBICION VAGAL
LIBERACION
SIMPATICA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
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Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
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Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
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MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SISTEMA LIMBICO rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
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rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
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BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
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BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
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Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
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rafaelporcilevaneduceduar
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Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
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Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
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SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
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La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
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angiotensina (1-7)
Su mecasismo es
PARACRINO
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La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
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Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
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Angiotensina II
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FUENTES DE
ANGIOTENSINA
II
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ALDOSTERONA
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ALDOSTERONA
ANGIOTENSINA II
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ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
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Proliferacioacuten colaacutegeno
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APOPTOSIS
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FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
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HORMAONA
ANTIDIURETICA
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ADH
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Reduccion de la natremia
ANGIOTENSINA II
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Angiotensina
III y
IV
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En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
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Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
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ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
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HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
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MECANISMOS
COMPENSADORES
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ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
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BARORECEPTORES AORTICOS Y
CAROTIDEOS
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
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ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
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MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
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Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
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Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
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SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
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Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
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Angiotensina II
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FUENTES DE
ANGIOTENSINA
II
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ALDOSTERONA
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ALDOSTERONA
ANGIOTENSINA II
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ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
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Proliferacioacuten colaacutegeno
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APOPTOSIS
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FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
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HORMAONA
ANTIDIURETICA
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ADH
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Reduccion de la natremia
ANGIOTENSINA II
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Angiotensina
III y
IV
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En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
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ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
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HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
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MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Sobrecarga adrenergics
bullMayor consumo de
oxigeno
bullReduccioacuten del potencial
de reposo status
arritmogenico
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
ACTIVACIOacuteN S R A A Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
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MECANISMOS
PSEUDOCOMPENSADORES
DE LA INSUFICIENCIA
CARDIacuteACA
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
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MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
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ALDOSTERONA
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ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
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Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
NUEVOS ACTORES
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La renina es una enzima
rafaelporcilevaneduceduar
Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
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rafaelporcilevaneduceduar
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Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
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Casi toda la renina encontrada en
los SRA locales se deriva de la
renina renal
Los sistemas locales estaacuten regulados
independientemente del SRA sisteacutemico
pero pueden interactuar con eacutel Se han
identificado SRA locales en el corazoacuten
rintildeoacuten cerebro paacutencreas aparato
reproductor sistema linfaacutetico y el
tejido adiposo
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
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Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
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Angiotensina II
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FUENTES DE
ANGIOTENSINA
II
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ALDOSTERONA
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ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
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En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
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Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
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ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
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HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
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MECANISMOS
COMPENSADORES
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ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
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Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
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Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Bajo flujo
Hipotensioacuten
arterial
Hipertension
arterial
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
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Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
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HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Enzima conversora de angiotensina 2
La ECA 2 es una carboxypeptidasa que se une a
un residuo de Ang I para generar Ang 1-9 y a un
residuo de Ang II para formar Ang 1-7 La ECA
2 rintildeoacuten corazoacutehipotaacutelamo y pared aoacutertica
testiacuteculos La ECA 2 y la Ang 1-7 modula la
actividad aumentada del SRA claacutesico
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Se considera que la angiotensina 1-9 es
inactiva y su funcioacuten bioloacutegica auacuten no esta
claramente definida pero estudios en ratas
demuestran que potencia la
vasoconstriccioacuten mediada por la
angiotensina II Adicionalmente tanto
en humanos como en ratas el nivel de
angiotensina 1-9 en plasma es el doble que
el de angiotensina II y la primera se
acumula en organismos que han sido
tratados con inhibidores de ECA
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina 1-9
Efecto protrombotico
reduciendo la fibrinoacutelisis
espontanea reduciendo la
concentracioacuten del activados
de plasminogeno en plasmina
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
SARA
LOCAL rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
El AGT y la renina provienen tanto de la
produccioacuten local como de la circulacioacuten La
ECA se expresa en cardiomiocitos y
fibroblastos al igual que el receptor de
prorrenina (RPR) que se une a eacutesta y facilita la
siacutentesis local de Ang II la cual tiene lugar tanto
en el espacio intersticial como a nivel
intracelular La siacutentesis extracelular de Ang II
depende generalmente de la prorrenina y la
ECA En cardiomiocitos la siacutentesis intracelular
de Ang II puede ocurrir en el citoplasma
mediada por renina y quimasa o en vesiacuteculas
secretoras rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La angiotensina (Ang) (1-7) es un
peacuteptido bioactivo del SRA que
provoca vasodilatacioacuten diuresis y
natriuresis lo cual favorece la
disminucioacuten de la presioacuten arterial
particularmente en situaciones de
actividad aumentada de la Ang II
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
angiotensina (1-7)
Su mecasismo es
PARACRINO
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La siacutentesis de la Ang 1-7 a partir de la
Ang I requiere de alguna de las
siguientes tres endopeptidasas tisulares
denominadas neprilisina prolil
endopeptidasa y timet oligopeptidasa
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
La disminucioacuten de la liberacioacuten de NA provocada
por la Ang-(1-7) podriacutea ser la consecuencia de una
inhibicioacuten de la siacutentesis del neurotransmisor asiacute
como de un aumento en su recaptacioacuten neuronal
dos procesos que contribuiriacutean a reducir la
concentracioacuten de neurotransmisor en el espacio
sinaacuteptico Recientemente demostramos
que la Ang-(1-7) presenta un efecto inhibidor sobre
la siacutentesis de NA por estimulacioacuten de la degradacioacuten
de la tirosina hidroxilasa
enzima que cataliza la
etapa inical y limitante
en la biosiacutentesis de
catecolaminas
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Relacioacuten ECAECA-2 Dependiendo del balance ECAECA-2
se obtendraacute los efectos de la Ang 1-7 o Ang II ya que si la relacioacuten ECAECA-2 es alta
se tendraacute mayores niveles de Ang II que de Ang 1-7 observaacutendose vasoconstriccioacuten
proliferacioacuten fibrosis
hipertrofia por su parte si la relacioacuten ECAECA-2 es baja se favorece la
formacioacuten de Ang 1-7 y predominaraacuten sus efectos
como la vasodilatacioacuten anti proliferacioacuten ECA Enzima Convertidora de Angiotensina ECA-2
Enzima Convertidora de Angiotensina - 2 (Tomado de Ferrario CM y col 1997 2006) [68] rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina II
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
FUENTES DE
ANGIOTENSINA
II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
ANGIOTENSINA II
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ALDOSTERONA
Retencion Na+
Retencion H2O
Excrecion K+
Excrecion Mg2+
Deposito de
colageno
Fibrosis - miocardica
- vascular
Edema
Arritmias
Competitive antagonist of the
aldosterone receptor
(myocardium arterial walls kidney)
ALDOSTERONA
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Proliferacioacuten colaacutegeno
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
APOPTOSIS
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
FIBROSIS
+apoptosis
+hipertrofia
Remodelacioacuten rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HORMAONA
ANTIDIURETICA
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ADH
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Reduccion de la natremia
ANGIOTENSINA II
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Angiotensina
III y
IV
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
En los gloacutebulos rojos existen
aminopeptidasas que inactivan a la Ang II
la que tiene una corta vida de
aproximadamente un minuto Estas
peptidasas convierten a la Ang II en
Angiotensina III (Ang III) que es un
heptapeacuteptido con el 50 de la actividad
presora de la primera y en el hexapeacuteptido
Angiotensina IV
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Las acciones de la
angiotensina II y Ang III
soacutelo son mediadas por los
receptores AT1 y AT2
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull RECEPTPRES ESPECIFICOS
ndash INSULIN REGULATED ANGIOTENSIN
PROTEIN IRAP ndash COMPARTEN CON LOS RECEPTORES DE
LA INSULINA A LA PROTEIONA
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4 rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANGIOTENSIONA IV
bull INHIBE LA DEGRADACION DE
ANGIOTENSINA II
bull GENERANDO UNA DOWN REGULATION DE
LVV HEMORFINA 7 TAMBIEN
ENCONTRADA EN LOS RECEPTORES
INSULINICOS GLUT 4
bull Down regulation de GLUT 4
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
HIPOPERFUSION RENAL
HEPATICA
CEREGRAL
MECANISMOS PSEUDO
COMPENSADORES
PRESIONES gt 16 mm Hg
CONGESTION RETROGRADA
MECANISMOS
COMPRNSADORES
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
MECANISMOS
COMPENSADORES
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ADRENOMEDULINA rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ADRENOMEDULINA
bull ORIGINALMENTE AISLADA EN LAS CELULAS
DEL FEOCROMOCITOMA ES DE PRODUCCION MULTITISULAR
bull SECUENCIA AMINOACIDA SIMILAR A LA CALCITONINA
bull EFECTO POTENTE VASODILATADOR
bull ANTAGONISTA ALDOSTERONICO
bull EFECTO INOTROPICO POSITIVO POR VIA
DEL AMP CICLICO (VIA EXCLUSIVA)
bull SU CONCENTRACION PLASMATICA Y TISULAR ES POTENCIADA EN LA INSUFICIENCIA CARDIacuteACA EN PROPORCION DIRECTA A LA PRESION EN LA ARTERIA PULMONAR Y AL GRADO DE DISFUNCIOacuteN VENTRICULAR
bull MECANISMO COMPENSADOR EN ICC COacuteNICA
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Plasma levels of adrenomedullin in
patients with mitral stenosis
Yamamoto et all Am Heart J 1998 Mar (3)542-9
bull Dosaje en sangre periferica
bull Notable incremento de
adrenomedulina directamente
proporcional a la presion en
arteria pulmonar
bull Significativa reduccioacuten de los dosajes
post valvuloplastia
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Plasma adrenomedullin as an independent
predictor of future cardiovascular events in
high-risk patients comparison with C-
reactive protein and adiponectin Nishida H Horio T Suzuki Y Iwashima Y Kamide K Kangawa K Kawano Y
Division of Hypertension and Nephrology Department of Medicine National Cardiovascular
Center 5-7-1 Fujishirodai Suita Osaka 565-8565 Japan
bull These findings indicate that plasma
AM is a powerful independent
predictor of future CV events in
high-risk patients suggesting its
predictive value is superior to that of
hs-CRP or adiponectin
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
PEPTIDOS ATRIALES
Y CEREBRALES
NATRIURETICOS Rafael Porcile
rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
ANP BNP
bull Brain Natriuretic Peptide
ndash 20 del ANP superando su concentracioacuten en IC
ndash Produccioacuten ventricular
bull Atrial Natriuretic Peptide
ndash Segregado por las celulas miocardicas en la
auricula en respuesta a la sobrecarga de volumen
ndash Polipeptido de entre 99 y 126 aa
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilisina
bull La neprilisina degrada los peacuteptidos
natriureacuteticos bioloacutegicamente
activos incluyendo ANP BNP y
CNP pero no es capaz de degradar
al NT-proBNP
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Neprilysin
zinc-dependent metalloprotease that cleaves peptides at
the amino side of hydrophobic residues and inactivates
several peptide hormones including glucagon
enkephalins substance P neurotensin oxytocin and
bradykinin[1] It also degrades the amyloid beta peptide
whose abnormal misfolding and aggregation in neural
tissue has been implicated as a cause of Alzheimers
disease Synthesized as a membrane-bound protein the
neprilysin ectodomain is released into the extracellular
domain after it has been transported from the Golgi
apparatus to the cell surface
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Insuficiencia cardiacuteaca
FISIOPATOLOGIA DE
SENDROMES CARDIO
SISTEMICOS
Rafael Porcile rafaelporcilevaneduceduar
D E P A R T A M E N T O D E C A R D I O L O G I A
C A T E D R A D E F I S I O L O G Iacute A
Universidad Abierta Interamericana
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 1
Pathophysiological interactions between heart and kidney in type 1 cardiorenal syndrome (CRS) or ldquoacute CRSrdquo (abrupt worsening
of cardiac function eg acute cardiogenic shock or acute decompensation of chronic heart failure) leading to kidney injury ACE =
angiotensin-converting enzyme ANP = atrial natriuretic peptide BNP = B-type natriuretic peptide CO = cardiac output GFR =
glomerular filtration rate KIM = kidney injury molecule N-GAL = neutrophil gelatinase-associated lipocalin RAA = renin
angiotensin aldosterone Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 2
Pathophysiological interactions between heart and kidney in type 2 cardiorenal syndrome (CRS) or ldquochronic CRSrdquo (chronic
abnormalities in cardiac function eg chronic heart failure) causing progressive chronic kidney disease (CKD) Figure illustration
by Rob Flewell LVH = left ventricular hypertrophy RAA = renin angiotensin aldosterone
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 3
Pathophysiological interactions between heart and kidney in type 3 CRS or ldquoacute renocardiac syndromerdquo (abrupt worsening of
renal function eg acute kidney failure or glomerulonephritis) causing acute cardiac disorder (eg heart failure arrhythmia
pulmonary edema) MPO = myeloperoxidase other abbreviations as in Figure 1 Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 4
Pathophysiological interactions between heart and kidney in type 4 cardiorenal syndrome (CRS) or ldquochronic renocardiac syndromerdquo
(chronic kidney disease [CKD] eg chronic glomerular disease contributing to decreased cardiac function cardiac hypertrophy or
increased risk of adverse cardiovascular events) BMI = body mass index EPO = erythropoietin LDL = low-density lipoprotein
Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
Date of download
9192014
Copyright copy The American College of Cardiology
All rights reserved
From Cardiorenal Syndrome
J Am Coll Cardiol 200852(19)1527-1539 doi101016jjacc200807051
CRS Type 5
Pathophysiological interactions between heart and kidney in type 5 cardiorenal syndrome (CRS) or ldquosecondary CRSrdquo (systemic
condition eg diabetes mellitus sepsis causing both cardiac and renal dysfunction) LPS = lipopolysaccharide (endotoxin) RVR =
renal vascular resistance Figure illustration by Rob Flewell
Figure Legend
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar
rafaelporcilevaneduceduar