general pathology
DESCRIPTION
General Pathology. Basic Principles of Cellular and Organ Pathology Blood Derived Pigments. Jaroslava Dušková Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague http://www1.lf1.cuni.cz/~jdusk/. Pigments. Definition Classification Blood pigment breakdown extravascular - PowerPoint PPT PresentationTRANSCRIPT
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General Pathology Basic Principles
of Cellular and Organ Pathology
Blood Derived Pigments
Jaroslava DuškováInst. Pathol. ,1st Med. Faculty, Charles Univ. Praguehttp://www1.lf1.cuni.cz/~jdusk/
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Pigments Definition Classification Blood pigment breakdown
– extravascular– intravascular
Hemosiderin– location– complications
Hemochromatosis Icterus
– definition– types– complications
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PigmentsDefinition:
colored substances in the organism
or environment
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PigmentsClassification: endogenous
– hemoproteins
derived– autogenous
exogenous
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Hemoproteins Derived Pigments
- colour substances originating from hemoglobin modification or breakdown
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daily iron need on average 1mg
losses : bile, sweat ….
turnover regulated by the HEPCIDIN
Iron metabolism
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Hepcidin (& Ferroportin) a 25-amino acid peptide hormone central regulator of body iron metabolism synthesized in the liver secreted in plasma binds to the cellular iron export channel
ferroportin causing its internalization and degradation, thereby
decreasing iron efflux from iron exporting enterocytes and macrophages into plasma
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Ferroportin a transmembrane protein that transports
iron from the inside of a cell to the outside of it.
found on the surface of cells that store or transport iron, including:– Enterocytes in the duodenum– Hepatocytes– Macrophages of the reticuloendothelial
system.
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Hemoproteins Derived Pigments oxyhemoglobin (Fe2+)
hematin (Fe3+) methemoglobin (globin + hematin) carboxyhemoglobin
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Blood Pigment Breakdown
extravascular intravascular
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ExtravascularBlood Pigment Breakdown
Hemoglobin heme oxygenase
biliverdin biliverdin reductase
bilirubin (cells of MPS) + globin + Fe
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ExtravascularBlood Pigment Breakdown
Globin aminoacids
Fe hemosiderin
Fe(OH)3 + protein carrier hematoidin = tissue bilirubin
(+ceroid)
Etymology: Gk: haima blood + sideros, iron
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Hemosiderin - Features
brown
forms a deep blue product Prussian
blue with acid potassium
ferocyanide solution
(Perls´ reaction)
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Hemochromatosis - life threatening complications
cirrhosis hepatocellular carcinomaheart failurearrhytmiadiabetes
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Blood Pigment Breakdown
extravascular intravascular
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IntravascularBlood Pigment Breakdown
Hemoglobin bound to haptoglobin (2– globulin) + Fe
biliverdinbilirubinurobilinogen enterohepatalstercobilinogen circulationurobilinstercobilin
norm in blood:1,7-17,4mmol/l
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Bilirubin Processing
transport to the liver
hepatocyte entry – hepatocyte blood pole
glucuronylation
output to bile - hepatocyte bile pole
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Icterus –Jaundice
Definition:
a condition in which the tissues are yellowish due to the
increase of bilirubin concentration
(normal plasma: 1,7-17,4 mmol/l unconj. bilirubin bound to albumin)
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Bilirubin Processing transport to the liver
hepatocyte entry – hepatocyte blood pole
glucuronylation
output to bile - hepatocyte bile pole
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Icterus – Jaundice generalized
– prehepatal flavin
– hepatal ruby
– posthepatal verdant icterus
melas
local– surrounding
hematoma
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Icterus
hemolytical (dynamic)
hepatocellular (dissociated)
obstructive (resorptive)
MIXED
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Icterus
hemolytical (dynamic)– corpuscular:
hered. spherocytosis, defect of G6P-dehydrogenase)
hemoglobinopathies
(sickle cell anemia, thalassaemiae)
– extracorpuscular(icterus neonati simplex, icterus neonati gravis…)
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Hemolytic Disease of the NewbornMorbus hemolyticus neonati –
erythroblastosis fetalis Rh- mother with an Rh+ fetus anti Rh IgG crossing the placenta barrier
– anaemia neonati
– icterus neonati gravis
– hydrops fetus universalis
– abortus
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Ceroid prevalence
– erythrocytes breakdown places
– fatty tissue necroses
– avitaminosis E
– melanosis coli
– Dubin - Johnson syndrome
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Icterus hepatocellular (dissociated)
– hepatotoxic – acquiredCCl4, amanitin,
hepatitis epidemica, febris flava,
leptospirosis, bact. sepsis...
– enzymopathies – inborn(Crigler–Najjar
Gilbert - glucuronyltransferase defect Dubin–Johnson, Rotor)
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Icterus
posthepatal – obstructive– acquired
obstruction– intraluminal– intramural,– extramural
– inborn(primary billiary atresia)
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Blockage of the Biliary Ways -causes
multiple intrahepatal
both right and left hepatic ducts
common hepatic duct
choledochus papilla Vateri
intraluminal - stone, ascaris…
intramural - non-neoplastic (inflamm.), neoplastic…
extramural – non-neoplastic,neoplastic
combined
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Blockage of the Biliary Ways - complications
icterus cholaemia cholangiogenic sepsis biliary cirrhosis bleeding disorders
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Icterus
hemolytical (dynamic)
hepatocellular (dissociated)
obstructive (resorptive)
MIXED
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Icterus Hemolytic Hepatocellular Obstructive
Cause Bilirubin (over)production
Input, conjug., output
Bile flow block
Serum bilirubin Unconj. Conj & unconj. Conj.
Urine -urobilin, stercobilin
0 + +++
Urine - urobilinogen
+++ ++ - 0
Feces -stercobilinogen
+++ + - -
Cholesterol +++
Bile acids +++