lp 1 proteine- 4.12.2014.ppt
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METABOLISMUL PROTEIC- PROTEINELE -
- DECEMBRIE 2014-
UNIVERSITATEA DE MEDICINI FARMACIE CAROL DAVILADIN BUCURETI,
FACULTATEA DE MEDICIN
DISCIPLINA FIZIOPATOLOGIE II
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CUPRINS
I. GENERALITATI
II. METODE DE INVESTIGARE A PROTEINELOR
1. Determinarea proteinelor serice totale2. Electroforeza proteinelor serice
3. Electroforeza cu imunofixare
4. Nefelometria
5. Electroforeza proteinelor urinare
III. VITEZA DE SEDIMENTARE A HEMATIILOR
IV. MODELE PROTEICE
V. PROTEINE ANORMALE
METABOLISMUL PROTEIC
- PROTEINELE -
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Proteinele- substaneorganice macromoleculare formate din lanurisimple saucomplexe de aminoacizi.
> 50% din greutatea uscata a organismului.
Compozitia chimica:
Holoproteine:
Scleroproteine (fibrilare): colagen, keratina, elastina.
Sferoproteine (globulare): globuline, albumine.
Heteroproteine:
glicoproteine
lipoproteine
nucleoproteine
http://www.britannica.com/EBchecked/topic/529155/scleroprotein
http://amit1b.wordpress.com/the-molecules-of-life/about/
I. GENERALITATIDEFINITIE SI CLASIFICARE
http://www.britannica.com/EBchecked/topic/529155/scleroproteinhttp://amit1b.wordpress.com/the-molecules-of-life/about/http://www.britannica.com/EBchecked/topic/529155/http://amit1b.files.wordpress.com/2008/03/enzyme_allostery_inhibitor.gifhttp://amit1b.wordpress.com/the-molecules-of-life/about/http://amit1b.wordpress.com/the-molecules-of-life/about/http://amit1b.wordpress.com/the-molecules-of-life/about/http://amit1b.wordpress.com/the-molecules-of-life/about/http://amit1b.wordpress.com/the-molecules-of-life/about/http://amit1b.wordpress.com/the-molecules-of-life/about/http://amit1b.wordpress.com/the-molecules-of-life/about/http://amit1b.wordpress.com/the-molecules-of-life/about/http://www.britannica.com/EBchecked/topic/529155/scleroprotein -
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Inflamatia (fizica, chimica, biologica) determina aparitia leziunilor celulare.
fragmentele rezultate din celulele distruse sunt fagocitate de macrofage si neutrofile;
in consecinta, macrofagele si neutrofilele elibereaza citokine proinflamatorii: IL-1, IL-6si TNF-.
la nivel hepatic, citokinele determina:
1. sinteza de proteine cu rol in procesul inflamator (proteine pozitive de faza
acuta);2. stoparea sintezeiunor proteine fara rol in infl amatie(proteine negative de faza
acuta), pentru a folosi resursele (aminoacizii) pentru sinteza proteinelor
pozitive de faza acuta.
INTREG PROCESUL=RASPUNS DE FAZA ACUTA
I. GENERALITATIRASPUNSUL DE FAZA ACUTA
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Inflamatie(fizica, chimica, biologica)
Leziuni celulare fragmente celulare
Macrofage, neutrofile
Citokine proinflamatorii (IL-1, IL-6, TNF-)
Ficat Proteine
Produce
Atrag
Produc
Actioneaza
I. GENERALITATIRASPUNSUL DE FAZA ACUTA
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Proteinele pozitive de faza acuta
1-antitripsina
1-glicoproteina acida
Componente ale complementului
Feritina 2-macroglobulina
Haptoglobina
Hepcidina
Fibrinogenul
Proteina C reactiva
Imunoglobulinele
http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350 http://www.copewithcytokines.de/cope.cgi?key=Acute%20phase%20proteins
I. GENERALITATIRASPUNSUL DE FAZA ACUTA
http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350 -
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Proteinele negative de faza acuta
Albumina Prealbumina
Transferina
Antitrombina
I. GENERALITATIRASPUNSUL DE FAZA ACUTA
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1. Determinarea proteinelor serice totale
2. Electroforeza proteinelor serice
3. Electroforeza cu imunofixare
4. Nefelometria
5. Electroforeza proteinelor urinare
http://www.goldsteig.de/de/karriere/ausbildung/milchwirtschaftlicher-laborantin.html
II. METODE DE INVESTIGARE A
PROTEINELOR
http://www.goldsteig.de/de/karriere/ausbildung/milchwirtschaftlicher-laborantin.html -
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Metoda spectrofotometrica (colorimetrica)
Principiu: trecerea luminii de lungime de unda cunoscuta printr-o proba si
masurarea modificarii lungimii de unda dupa pasajul prin cuva de testare.
Proteinemia (protidemia)concentratia plasmatica a proteinelor serice
(PT=proteine totale).Valori normale PT6,58,5 g/dl.
http://chemwiki.ucdavis.edu/Physical_Chemistry/Kinetics/Reaction_Rates/Experimental_Determination_of_Kinetcs/Spectrophotometry
II. METODE DE INVESTIGARE A PROTEINELOR1.DETERMINAREA PROTEINELOR SERICE TOTALE
http://chemwiki.ucdavis.edu/@api/deki/files/8475/spectrophotometer_structure.png -
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Valoarea plasmatica a PT depinde de:- aportul proteic,
- absorbtia la nivel intestinal,
- sinteza hepatica,
- catabolism,
- pierderi (pe cale renala, digestiva, cutanataarsuri intinse).
Indicatii pentru dozarea PT:
- sindroame de malnutritie;
- sindroame de malabsorbtie;
- afectiuni insotite de insuficienta hepatica;
- afectiuni insotite de hipercatabolism proteic;
- afectiuni care evolueaza cu pierderi de proteine.
II. METODE DE INVESTIGARE A PROTEINELOR1.DETERMINAREA PROTEINELOR SERICE TOTALE
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Hiperproteinemia (PT > 8,5 g/dl)
reala
-aport alimentar crescut (suplimente proteice, diete hiperproteice)-boli hematologice (boli hematologice cu sinteza anormal crescuta de proteine)
aparenta
sindroame de hemoconcentraie (n deshidratari).
II. METODE DE INVESTIGARE A PROTEINELOR1.DETERMINAREA PROTEINELOR SERICE TOTALE
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Hipoproteinemia (PT < 6,5 g/dl)
reala
- aport scazut (malnutritie, vegetarieni)-scderea absorbiei intestinale(boli inflamatorii intestinale)-scderea sintezei(insuficienta hepatica)-pierderi proteice (sd nefrotic, enteropatii, arsuri pe suprafete intinse);
-sechestrare proteic(ocluzia intestinala, ascita);
-hipercatabolism proteic (hipertiroidism sever, tuberculoza, neoplazii).
aparenta- sindoame de hemodiluie (n hiperhidratare).
II. METODE DE INVESTIGARE A PROTEINELOR1.DETERMINAREA PROTEINELOR SERICE TOTALE
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Metoda calitativa de separare a proteinelor serice,pe baza mobilitii n cmp
electric (se efectueaza si pentru proteinele din urina, saliva, LCR).
Viteza de migrare a proteinelor - invers proportionalacu greutatea moleculara,
- direct proportionalacu sarcina electric.
Ordinea fraciunilor, de la anod la catod: albumine, alfa1, alfa2, beta, gama globuline.
Migrarea se face la un pH de 8,6.
Mediile de migrare:
- gel: agar, agaroz(dureaza pn la 24h);
- folii de acetat de celuloz i poliacril-
amid(dureaz 2-3h);
- hrtii de filtru.
http://cg.scs.carleton.ca/~morin/teaching/compbio/electro.html
II. METODE DE INVESTIGARE A PROTEINELOR2. ELECTROFOREZA PROTEINELOR SERICE
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Placa obinut se compar cu o plac standard si se evalueaza:
- grosimea benzilor;
- intensitatea culorii benzii
(la hrtiile de filtru);
- sediul migrrii.
Indicatii:
- inflamaii acute, cronice;
- afectiuni hematologice;
- afectiuni hepatice;
- boli autoimune;
- afectiuni renale/intestinale
cu pierdere proteine.
http://flickrhivemind.net/Tags/electrophoresis/Interesting
II. METODE DE INVESTIGARE A PROTEINELOR2. ELECTROFOREZA PROTEINELOR SERICE
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Un comportament normal la electroforez = euproteinemieValori normale PT= 6.5 - 8,5 g
Raport albumine/globuline =1,3 - 1,5
Albumine : 5060 % (3,55,5 g/dL)
Alfa 1 globuline : 3 - 4 %
Alfa 2 globuline : 6 - 9 % Globuline=2.3-3.4 g/dL
Beta globuline : 10 - 12 %
Gama globuline : 1820 %
http://www.biometria.ro/Kit-pentru-determinarea-electroforetica-pe-gel-de-agaroza-a-proteinelor-
II. METODE DE INVESTIGARE A PROTEINELOR2. ELECTROFOREZA PROTEINELOR SERICE
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Zona albumine i alfa1
globuline :
Prealbumina
Albumina
Alfa1-antitripsina
Alfa1-glicoproteinaacid
Alfa-fetoproteina
Protrombina
II. METODE DE INVESTIGARE A PROTEINELOR
2. ELECTROFOREZA PROTEINELOR SERICE
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ZONA ALBUMINE
Prealbumina
thyroid binding prealbumin (TBPA),
tiretina, transtiretina;
Valori normale serice:15-36 mg/dl.
Sintetizata hepatic.
Rol :transportul hormonilor tiroidieni.
T (1,9 zile) vs albumina (21 zile)indicator mai bun al afectarii acute a funcieidesinteza hepatica.
Scade:- deficit de sinteza
- compensator cresterii sintezei proteinelor de faza acuta (inflamaii) -protein negativ de faz acut
- afectiuni hepatice cu insuficienta hepatica
- pierdere de proteine (afectiuni renale/intestinale)http://medicine.creighton.edu/medschool/WebAtlas/secure/hemonc/immmunoglob/07pre.htm
II. METODE DE INVESTIGARE A PROTEINELOR2. ELECTROFOREZA PROTEINELOR SERICE
http://medicine.creighton.edu/medschool/WebAtlas/secure/hemonc/immmunoglob/07pre.htm -
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ZONA ALBUMINE
AlbuminaValori normale serice: 3,5-5 g/dl.
sintetizata hepatic, reprezinta 60% din proteinele serice;
Rol :- mentinerea presiunii coloid-osmotice
- transport hormoni, enzime, metale, etc.
T al albuminei (21 zile) - afectarea hepatic cu afectarea sintezei albuminei se va evidenia dupcteva sptmni de la instalare.
valori crescute(hemoconcentratie).
valori scazute (hipoalbuminemia = principala cauza de hipoproteinemie):
- deficit de aport (malnutritie)
- deficit de absorbtie (enteropatii),
- deficit de sinteza
- compensator cresterii sintezei proteinelor de faza acuta (inflamaii) -protein negativ de faz acut .
- insuficienta hepatica
- pierdere de proteine (sindrom nefrotic)
- scadere relativ (aparenta) in hemodilitii (prin hiperhidratare).http://www.liquidarea.com/2009/05/livelli-di-albumina-e- rischi-trombosi/
II. METODE DE INVESTIGARE A PROTEINELOR2. ELECTROFOREZA PROTEINELOR SERICE
http://www.liquidarea.com/2009/05/livelli-di-albumina-e-%20rischi-trombosi/http://www.liquidarea.com/2009/05/livelli-di-albumina-e-%20rischi-trombosi/http://www.liquidarea.com/2009/05/livelli-di-albumina-e-%20rischi-trombosi/http://www.liquidarea.com/2009/05/livelli-di-albumina-e-%20rischi-trombosi/http://www.liquidarea.com/2009/05/livelli-di-albumina-e-%20rischi-trombosi/http://www.liquidarea.com/2009/05/livelli-di-albumina-e-%20rischi-trombosi/http://www.liquidarea.com/2009/05/livelli-di-albumina-e-%20rischi-trombosi/http://www.liquidarea.com/2009/05/livelli-di-albumina-e-%20rischi-trombosi/http://www.liquidarea.com/2009/05/livelli-di-albumina-e-%20rischi-trombosi/http://www.liquidarea.com/2009/05/livelli-di-albumina-e-%20rischi-trombosi/http://www.liquidarea.com/2009/05/livelli-di-albumina-e-%20rischi-trombosi/http://www.liquidarea.com/2009/05/livelli-di-albumina-e-%20rischi-trombosi/http://www.liquidarea.com/2009/05/livelli-di-albumina-e-%20rischi-trombosi/ -
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ZONA ALFA 1 GLOBULINE
Alfa1-antitripsina (AAT)- Sinteza hepatica
- 90% din zona alfa 1 globuline !
Rol: antiproteaza (inhiba proteazele:
protrombina, plasmina, kalicreina,
elastaza, colagenaza etc.).Valori crescute: http://www.drbayma.com/conheca-a-deficiencia-de-alfa-1-antitripsina/
- inflamatii acute/inflamatii cronice acutizate - proteina pozitiva de faza acuta.
Valori scazute:
- deficit congenital (emfizem);
- deficit dobandit:
- deficit de aport (malnutritie),
- deficit de sinteza (afectiuni cu insuficienta hepatica),
- pierdere proteine (sindrom nefrotic, enteropatii etc.)
- consum crescut, in contextul excesului de proteaze (CID).
CID(Coagulare Intravasculara Diseminata) = exacerbarea cascadei coagularii la nivel vascular sistemic; apare in
infectiile severe, complicatiile obstetricale, hemoliza intravasculara, traumatisme severe, hipoxii severe etc.
II. METODE DE INVESTIGARE A PROTEINELOR2. ELECTROFOREZA PROTEINELOR SERICE
http://www.google.ro/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&docid=NJJr3FNJkmSfYM&tbnid=XMM6XYxCclyZgM:&ved=0CAUQjRw&url=http://www.drbayma.com/conheca-a-deficiencia-de-alfa-1-antitripsina/&ei=xcOHUoafAoHVtQaPhIDQCg&bvm=bv.56643336,d.bGE&psig=AFQjCNHSbzzA8U7BZgx2W3nbZpfURdkelw&ust=1384715571964681 -
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ZONA ALFA1 GLOBULINE
Alfa 1-glicoproteina acidglicoprotein (proporie peptidic=58%)
sinteza hepatica.
Rol: - transport (colesterol, vitamina B12),
- imunomodulator(maturarea limfocitelor B),
- apararea nespecifica (fagocitoza).
Valori crescute:
- inflamatii acute/inflamatii cronice acutizate
(proteina pozitiva de faza acuta)
Valori scazute:
- deficit de aport (malnutritie)
- deficit de sinteza (insuficienta hepatica)
- pierdere proteine (sindrom nefrotic)
http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350
II. METODE DE INVESTIGARE A PROTEINELOR2. ELECTROFOREZA PROTEINELOR SERICE
http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350http://www.studyblue.com/notes/note/n/test-2-acute-inflammation-systemic-effects/deck/2284350 -
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II. METODE DE INVESTIGARE A PROTEINELOR
2. ELECTROFOREZA PROTEINELOR SERICE
Zona alfa2 globuline:
Haptoglobina
Ceruloplasmina
Alfa2 macroglobulina Colinesteraza
Alfa2 antitrombina
Plasminogen
Transcortina
Eritropoietina
Componentele C1, C4,C6,C9 ale complementului
Lipoproteine
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ZONA ALFA 2 GLOBULINE
Haptoglobina(Hp)Glicoproteina sintezata hepatic
Rol:legarea Hb libere
Valori crescute:
- inflamatii acute/inflamatii cronice acutizate
(proteina pozitiva de faza acuta)
Valori scazute:
- deficit genetic (ahaptoglobulinemia congenitala)
- deficit dobandit
- sinteza scazuta (insuficienta hepatica)
- consum crescut (hemoliza intravasculara)
Hp serice + functie hepatica N => consumul crescut de Hp in hemoliza intravasculara
Concentratia plasmatica nu se modifica in icterele obstructive (diagnostic diferential
intre icterele hemolitice si cele obstructive)http://www.umass.edu/karbon13/images/Haptoglobin%20for%20webpage.jpg
II. METODE DE INVESTIGARE A PROTEINELOR2. ELECTROFOREZA PROTEINELOR SERICE
http://www.umass.edu/karbon13/images/Haptoglobin%20for%20webpage.jpghttp://www.google.ro/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&docid=5JNdvNl0f3MeKM&tbnid=c6kejbOF7e4yTM:&ved=0CAUQjRw&url=http://meddic.jp/haptoglobin&ei=AM-HUpecL8nMtAbhtYG4Cw&bvm=bv.56643336,d.bGE&psig=AFQjCNFj1Dc168fslxFab7cWK7n-vEK6Zg&ust=1384718461627099http://www.umass.edu/karbon13/images/Haptoglobin%20for%20webpage.jpghttp://www.umass.edu/karbon13/images/Haptoglobin%20for%20webpage.jpghttp://www.umass.edu/karbon13/images/Haptoglobin%20for%20webpage.jpg -
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ZONA ALFA 2 GLOBULINE
Ceruloplasmina
Sinteza hepatica.
Rol:
-transporta 70% dincuprul (Cu) seric
total.
- feroxidaza (oxideaza Fe2+ => Fe3+)
reactie ce precede incorporarea Fe
in apotransferine.
Valori crescute:
- inflamatii acute/inflamatii cronice acutizate -proteina pozitiva de faza acuta.
- alterarea excretiei cuprului, ca urmare a colestazei (Cu se elimina 80% pe cale biliara)sindroame colestatice.
II. METODE DE INVESTIGARE A PROTEINELOR2. ELECTROFOREZA PROTEINELOR SERICE
Fiziopatologie Atlas color, Stefan Silbernagl, Florian Lang, EdituraCallisto,
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ZONA ALFA 2 GLOBULINE
Ceruloplasmina
Valori scazute:
- deficit genetic (afectiuni ereditare - boala Wilson),
- deficit dobandit
- deficit de aport (malnutritie)
- deficit de absorbtie (enteropatii),
- deficit de sinteza (insuficienta hepatica)
- pierdere de proteine (sindrom nefrotic).
II. METODE DE INVESTIGARE A PROTEINELOR2. ELECTROFOREZA PROTEINELOR SERICE
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ZONA ALFA 2 GLOBULINE
CeruloplasminaBoala Wilson (degenerescenta hepatolenticulara)
- afectiune ereditara - gena anormala = ATP7B (cromozom 13), codifica proteinatransportoare a cuprului
- diminuarea excreiei biliare a cuprului, n condiiile unei absorbii intestinale
i transportului spre hepatocit neafectate.
- consecinta = acumularea cuprului in organe ( ficat , creier, ochi, cord, pancreas, os), cu
aparitia:
- cirozei hepatice
- tulburarilor neurologice
- inelului Kayser- Fleischer
- afectarii cardiace, pancreatice si osoase
Fiziopatologie Atlas color, Stefan Silbernagl, Florian Lang, Editura Callisto,
II. METODE DE INVESTIGARE A PROTEINELOR2. ELECTROFOREZA PROTEINELOR SERICE
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ZONA ALFA 2 GLOBULINE
Alfa 2 macroglobulina
Cea mai mare proteina plasmatica
nonimunoglobulinica (725 kDa)
Sinteza hepatica
Rol : antiproteaza, imunomodulator
Valori crescute:
- inflamatii acute/inflamatii cronice acutizate (proteina pozitiva de faza acuta) .
- sindromul nefrotic (greutate moleculara mare si nu se pierde la nivel renal).
Valori scazute:
- insuficienta hepaticaHttp://universitam.com/academicos/?p=17049
II. METODE DE INVESTIGARE A PROTEINELOR2. ELECTROFOREZA PROTEINELOR SERICE
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Metoda de investigare
noninvaziva a functiei hepatice
Evalueaza gradul afectarii hepatice
Alternativa la biopsie hepatica
Algoritm:
- markeri biochimici serici: alfa-2macroglobulina, haptoglobina, apolipoproteina A1,
bilirubina totala, GGT, ALT, AST, glicemie bazala, colesterol, trigliceride
- varsta, sexul, greutatea si inaltimea
Cupride 5 teste:
FibroTest- gradul fibrozei (F0-F4).
ActiTest - gradul de activitate necro-inflamatorie (A0-A3).
SteatoTest- steatoza hepatica (S0 -S3).
NashTest- prezenta steatohepatitei non-alcoolice (N0-N2)
AshTest - gradul afectarii hepatice, la pacientii cu un consum excesiv de etanol (H0-H3).http://www.lab21.eu/healthcare/fibromax.php
FIBROMAX
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Zona beta globul ine:
Beta2 microglobulina
Transferina
Lizozim
Beta-lipoproteinele
Complement- C3
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2. ELECTROFOREZA PROTEINELOR SERICE
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ZONA BETA GLOBULINE
II. METODE DE INVESTIGARE A PROTEINELOR2. ELECTROFOREZA PROTEINELOR SERICE
Beta2 microglobulina Sintetizata de limfocite.
Rol:
- Fixata de membranele celulare;
- Formeaza lantul scurt al HLA tip I-
prezent in membrana tuturor celulelor nucleate.
Valori crescute:
- in toate afectiunile cu proliferare limfocitara:
(ex: boli hematologice, boli autoimune);
Valori scazute:
- in toate afectiunile cu distrugere celulara:
(ex: infectia HIV/SIDA, neoplazii).
http://en.wikipedia.org/wiki/File:MHC_Class_1.svg
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Transferina Glicoproteina (siderofilina, beta1 globulina)
Valori normale=200-400 mg/dl;
Sinteza hepatica
Rol:proteina ce transporta Fe la tesuturi
Valori crescute:
- rata de sinteza e invers proportionala cu depozitele de fier (ex: anemie
feripriva)
Valori scazute:
- sinteza supresata in cursul proceselor de faza acuta (inflamatii acute/cronice),
- deficit de sinteza (afectiuni hepatice cu insuficienta hepatica)
- cresterea saturatiei cu fier a feritinei determina scaderea sintezei
transferinei (hemocromatoza)htt ://www.cdc. ov/ncbddd/hemochromatosis/trainin / atho h siolo /iron c cle o u .htm
2. METODE DE INVESTIGARE A PROTEINELOR2. ELECTROFOREZA PROTEINELOR SERICE
ZONA BETA GLOBULINE
http://www.cdc.gov/ncbddd/hemochromatosis/training/pathophysiology/iron_cycle_popup.htmhttp://www.cdc.gov/ncbddd/hemochromatosis/training/pathophysiology/iron_cycle_popup.htmhttp://www.cdc.gov/ncbddd/hemochromatosis/training/pathophysiology/iron_cycle_popup.htmhttp://www.cdc.gov/ncbddd/hemochromatosis/training/pathophysiology/iron_cycle_popup.htmhttp://www.cdc.gov/ncbddd/hemochromatosis/training/pathophysiology/iron_cycle_popup.htm -
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II. METODE DE INVESTIGARE A PROTEINELOR
2. ELECTROFOREZA PROTEINELOR SERICE
Zona gama globuline:
Fibrinogen
Proteina C reactiva
Imunoglobuline
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ZONA GAMA GLOBULINE
Fibrinogenul
Valori normale: 150-450 mg/dl;
sintetizat de ficat.
Rol : in hemostaza
(factorul I al coagularii)
Valori crescute:
- inflamatii acute/cronice acutizate, neoplazii (proteina pozitiva de faza acuta),
- raspuns compensator la pierderea de proteine - pierderea prin urina a albuminei
(sindromul nefrotic ).
http://www.bmsc.washington.edu/people/teller/fig1.gif
II. METODE DE INVESTIGARE A PROTEINELOR
2. ELECTROFOREZA PROTEINELOR SERICE
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ZONA GAMA GLOBULINE
Fibrinogenul
Valori scazute:
deficit dobandit:
- deficit de aport (malnutritie),
- deficit de sinteza (insuficienta hepatica),
- exces de fibrinoliza (CID)
deficit congenitaldeficit de sinteza (afibrinogenemia congenitala)
CID(Coagulare Diseminata Intravasculara )=exacerbarea cascadei coagularii la nivel sistemic; apare in infectiile severe,
complicatiile obstetricale, hemoliza intravasculara, colagenoze, traumatisme severe.
http://www.bmsc.washington.edu/people/teller/fig1.gif
II. METODE DE INVESTIGARE A PROTEINELOR
2. ELECTROFOREZA PROTEINELOR SERICE
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ZONA GAMA GLOBULINE
Proteina C reactiva (CRP)
Valori normale 0-5 mg/dl.
-sinteza hepatica
Rol
- clearance-ul detritusurilor celulare
- opsonizare
- activarea complementului
pe calea clasica (se leaga de fractiunea C1q)
http://www.portalesmedicos.com/publicaciones/articles/4581/1/
II. METODE DE INVESTIGARE A PROTEINELOR
2. ELECTROFOREZA PROTEINELOR SERICE
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ZONA GAMA GLOBULINE
Proteina C reactiva
Valori crescute:
- inflamatii acute sau cronice acutizate, neoplazii
(proteina pozitiva de faza acuta )
- orice afectiune care implica un proces inflamator :
- infectii bacteriene
- boli autoimune, boli inflamatorii intestinale,
- traumatisme,
- arsuri,
- interventii chirurgicale.
Valori scazute:
- tratamentul cu antiinflamatorii (nonsteroidiene, corticosteroizi).
-
http://www.portalesmedicos.com/publicaciones/articles/4581/1/
II. METODE DE INVESTIGARE A PROTEINELOR
2. ELECTROFOREZA PROTEINELOR SERICE
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Imunoglobulinele
Sinteza in limfocite.
Structura:
-2 lanturi usoare (L),
-2 lanturi grele (H).
- legate prin punti disulfidice.
Clase : Ig G, Ig A, IgM, IgD, IgE
Rol: in raspunsul inflamator
Legarea specifica a Ag;
Activarea complementului;
Modularea raspunsului imun;
http://anamedex.ro/recipe/show/47/imunograma
II. METODE DE INVESTIGARE A PROTEINELOR
2. ELECTROFOREZA PROTEINELOR SERICE
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II. METODE DE INVESTIGARE A PROTEINELOR3. ELECTROFOREZA PROTEINELOR CU IMUNOFIXARE
Indicatii:
Aparitia la electroforeza proteinelor serice a unui varf in zona gama
Existenta unei suspiciuni clinice de gamapatie monoclonala
Metoda permite diferentierea intre homogenitatea sau heterogenitatea
componentelor varfului electroforetic.
Principiu:- marcarea diferita a fractiunilor de Ig si a
lanturilor usoare ale Ig obtinute prin
migrare in campul electroforetic
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Component monoclonal
- SP = marcarea tuturor claselor de Ig
- G, A, M = reprezinta lanturile grele
ale proteinelor Ig G, Ig A, IgM- , = lanturile usoare ale Ig
Component policlonal
- Se constata benzi mai largi in
zonele de migrare a tuturorclaselor de Ig
3. ELECTROFOREZA PROTEINELOR CU IMUNOFIXARE II.
METODE DE INVESTIGARE A PROTEINELOR
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Peak monoclonal(proliferarea unei singure clone LB):
- afectiuni hematologice cu producere de proteine anormale (ex.
macroglobulinemia Waldenstrom, mielom multiplu).
Peak policlonal(proliferarea mai multor clone de LB):
- boli autoimune,
- inflamatii cronice,
- afectiuni hepatice:
- ciroza hepatica,
- hepatite cronice virale.
II. METODE DE INVESTIGARE A PROTEINELOR3. ELECTROFOREZA PROTEINELOR CU IMUNOFIXARE
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Imunoglobulina A
Valori normale: 60-400 mg/dl.
Rol:
- imunitatea mucoaselor
(se secreta 3-5 g/zi in intestin).
- in secretiile digestive, genito-urinare, lacrimale, saliva, lapte matern.
Valori crescute:
- sinteza crescuta de proteine anormale Ig A-like (mielom IgA);
- afectiuni intestinale cu lezarea mucoasei tubului digestiv;
- lezarea mucoasei cu patrunderea agentilor patogeni prin mucoasasi cresterea secundara a Ig A (alcoolism).
Valori scazute:
- deficit congenital de Ig A (in cadrul agamaglobulinemiei).
- scaderea numarului de limfocite si sinteza cu defect de Ig A (ataxia
teleangiectazia-afectiune genetica caracterizata prin telangiectazii, ataxie si ale tulburari neurologice
).
II. METODE DE INVESTIGARE A PROTEINELORIMUNOGLOBULINELE
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Imunoglobulina M
Valori normale:60-300 mg/dl.
Exprimata pe suprafata LB sau libera in ser.
Rol:
- primii anticorpi- apar in cursul unei infectii.- marker inflamatie acuta.
Formeaza polimeride aceea nu traverseaza bariera placentara.
Valori crescute:
-infectii acute/cronice acutizate,
- status proinflamator cu eliberare de citokine cu rol de cofactor in sinteza deimunoglobuline, inclusiv Ig M (boli autoimune).
- afectiuni hematologice cu sinteza crescuta de Ig M-like (macroglobulinemiaWaldenstrom).
http://oregonstate.edu/instruct/bb451/spring13/lectures/immunesystoutline.html
II. METODE DE INVESTIGARE A PROTEINELORIMUNOGLOBULINELE
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Imunoglobulina M
Valori scazute:
- deficit congenital de Ig M in cadrul agamaglobulinemiei.
- imaturitatea sistemului imun cu deficit de sinteza de imunoglobuline
inclusiv Ig M (nou nascut).
Observatie: Proliferarea unor clone limfocitare catre o clasa de imunoglobuline areconsecinta scaderea compensatorie a celorlalte clase de imunoglobuline.
http://oregonstate.edu/instruct/bb451/spring13/lectures/immunesystoutline.html
II. METODE DE INVESTIGARE A PROTEINELORIMUNOGLOBULINELE
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Imunoglobulina D
Valori normale:0-14 mg/dl
Rol:
-activarea LB, bazofilelor si mastocitelor.
Exprimata pe suprafata LB imature (naive) alaturi de IgM sau libera in ser ca
monomer.
Valori crescute:
- infectii acute/cronice acutizate,
-status proinflamator cu eliberare de citokine cu rol de cofactor in
sinteza de imunoglobuline (boli autoimune). Valori scazute:
- deficit congenital de Ig D (agamaglobulinemie),
- imaturitatea sistemului imun cu deficit de sinteza deimunoglobuline, inclusiv Ig D (nou nascut).
http://oregonstate.edu/instruct/bb451/spring13/lectures/immunesystoutline.html
II. METODE DE INVESTIGARE A PROTEINELORIMUNOGLOBULINELE
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Imunoglobulina E
Valori normale:7-15 mg/dl.
Rol:
-declansarea reactiei reactiei
alergice, tip I. Ag e recunoscut de Ig E => activare secundara a mastocitelor, bazofilelor
degranularea acestora cu eliberare de mediatori proinflamatori.
severitatea reactiei pana la instalarea starii de soc (soc anafilacticreactie dehipersensibilitate tip I).
Valori crescute:- boli atopice (astm bronsic alergic, eczema atopica),
- parazitoze (giardioza, echinoccocoza, teniaza, trichineloza, malarie).
Valori scazute:
-deficit congenital de Ig E (agamaglobulinemie).htt ://ore onstate.edu/instruct/bb451/s rin 13/lectures/immunes stoutline.html
II. METODE DE INVESTIGARE A PROTEINELORIMUNOGLOBULINELE
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Imunoglobulina G
Valori normale:700-1500 mg/dl.
aprox 75% din Ig serice.
Rol:
- raspunsul imun secundar/tardiv.
- marker de inflamatie cronica.
- confera protectie Ag specifica. Singurul izotip de Ig care traverseaza placenta, conferind protectie imuna in utero.
Valori crescute:
- infectii acute/cronice acutizate,
- status proinflamator cu eliberare de citokine cu rol de cofactor insinteza de imunoglobuline, inclusiv Ig G (boli autoimune).
- afectiuni hematologice cu sinteza crescuta de proteine anormale Ig G- like.
Valori scazute:
- deficit congenital (agamaglobulinemie),
- pierdere urinara de proteine (sindrom nefrotic).
http://oregonstate.edu/instruct/bb451/spring13/lectures/immunesystoutline.html
II. METODE DE INVESTIGARE A PROTEINELORIMUNOGLOBULINELE
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II. METODE DE INVESTIGARE A PROTEINELOR4. NEFELOMETRIA
Metoda cea mai folosit n prezent
Principiu:reaciei Ag-Ac, (Ag =proteinele plasmatice, iar Ac = Ac antiprotein uman). Dac nu exist complexe Ag-Ac, fasciculul de lumin trece nedeviat i e captat de detectorul
de transmisie.
Dac se formeaz complexe, unele raze sunt deviate i sunt captate de detectorul de difuzie.
Exist dou submetode: Turbidimetriaapreciaz concentraia de Ag n funcie de cantitatea de lumin captat de
detectorul de transmisie Nefelometria propriu-zis apreciaz ct lumin e deviat i captat de detectorul de difuzie. Ulterior se face corelaia ntre cantitatea de lumin captat i concentraia Ag (respectiv a
proteinelor).
Metoda este rapid, sensibil, automatizat, dar este scump.
II METODE DE INVESTIGARE A PROTEINELOR
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II. METODE DE INVESTIGARE A PROTEINELOR5. ELECTROFOREZA PROTEINELOR URINARE
combina electroforeza cu imunoprecipitarea, folosind antiseruri monospecificefata de lanturile grele si usoare ale Ig;
Identifica prezenta lanturile usoare monoclonale in urina (proteinurie Bence
Jones).
10 ml din urina/24h.
Indicatii:
- peak gama la electroforeza proteinelor serice;- identificare proteine urinare Bence Jones (mielom multiplu, macroglobulinemia
Waldenstrom).
http://www.myelomapennstate.net/Contents/12c-Lab.htm
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III. VITEZA DE SEDIMENTARE A HEMATIILOR (VSH)
Valori normale: 2-30 mm/h
Reprezinta proprietatea hematiilor de a
sedimenta in vitro.
Proba de snge trebuie
tratat n prealabil cu anticoagulant (pentru evitarea coagularii).
Principiu:
In mod normal, hematiile sedimenteaza lent, datorita incarcaturii negative de suprafata,
care determina respingerea lor, cand distanta dintre hematii scade sub un nivel minim.
In afectiunile care determina cresterea proteinelor de faza acuta sau a imunoglobulinelor -
proteinele plasmatice se aseaza pe suprafata hematiilor si reduc potentialul de suprafatadeterminand agregarea hematiilor si cresterea sedimentarii acestora.
Reacie de disproteinemie, ntruct modificrile sale sunt condiionate de modificrilecantitative ale fibrinogenului i -globulinelor.
http://www.lt-burnik.si/eng/Index.php?id=./01_Products/03_ESR/03_Sediko/Index.html
http://www.google.ro/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&docid=j2yKEheMdmllmM&tbnid=9aatKUqgic2a4M:&ved=0CAUQjRw&url=http://www.lt-burnik.si/eng/Index.php?id=./01_Products/03_ESR/03_Sediko/Index.html&ei=hn2IUpK9HIbWtAak_oHYCg&bvm=bv.56643336,d.bGE&psig=AFQjCNFMu9r3xzoG4Bc1uB8pMAFc7czchw&ust=1384763116429253 -
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Valori crescute:
- infectii/inflamatii acute/cronice,
- neoplazii,
- boli autoimune,
- afectiuni hematologice cu cresterea imunoglobulinelor serice.
Valori scazute:
- policitemia (numar crescut de hematii),
- hipofibrinogenemia.
http://www.lt-burnik.si/eng/Index.php?id=./01_Products/03_ESR/03_Sediko/Index.html
III. VITEZA DE SEDIMENTARE A HEMATIILOR (VSH)
IV MODELE PROTEICE
http://www.google.ro/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&docid=j2yKEheMdmllmM&tbnid=9aatKUqgic2a4M:&ved=0CAUQjRw&url=http://www.lt-burnik.si/eng/Index.php?id=./01_Products/03_ESR/03_Sediko/Index.html&ei=hn2IUpK9HIbWtAak_oHYCg&bvm=bv.56643336,d.bGE&psig=AFQjCNFMu9r3xzoG4Bc1uB8pMAFc7czchw&ust=1384763116429253 -
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Inflamatia acutamodificari electroforetice
Reprezinta raspunsul imediat, de aparare al tesuturilor vii la agresiune.
Alfa1 i alfa2 globulinele crescute
Celelate benzi sunt in limite normalesau scazute relativ, compensator la cresterea
alfa 1 si alfa2 globulinelor.
In inflamaiile acute din arsuri ntinsepoate aparea hipoalbuminemie.
Alte teste:
PT - normale
Fibrinogenul crescut
Proteina C reactiva crescuta
VSH crescut
http://pro2services.com/lectures/Winter/Proteins/protein.htm
IV. MODELE PROTEICE
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Patternurile caracteristice ale modificarilor concentraiilor plasmatice a unor proteine
de faza acut , dup un stimul inflamator
http://www.synevo.ro/proteine-si-teste-de-inflamatie/
IV. MODELE PROTEICE
http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/http://www.synevo.ro/proteine-si-teste-de-inflamatie/ -
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Inflamatia cronicamodificari electroforetice
Inflamatie de lunga durata (saptamani, luni), ce presupune: inflamatie activa, distructietisulara si reparare conjunctiva.
Gama globulinele crescute.
Celelate benzi sunt in limite normalesau scazute relativ compensator la cresterea
gama globulinelor.
In inflamaiile acute din arsuri ntinsepoate aparea hipoalbuminemie.
Alfa1 i alfa2 globulinele pot avea
valori crescute=> acutizare a afeciunii cronice.
Alte teste:
PT N sau uor crescute. Fibrinogenul crescut
Proteinei C reactiva creste (necaracteristic)
VSH crescuthttp://pro2services.com/lectures/Winter/Proteins/protein.htm
IV. MODELE PROTEICE
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Sindrom nefroticmodificari electroforetice
- pierdere proteine > 3,5 g/24 ore
- sindrom nefrotic purse pierd albumine- sindrom nefrotic impurse pierd albumine si globuline
Albuminele sczute(< 2 g % - apar edeme) alfa 2 globulinele i beta globulinelecrescute
cretere n band (nu trec prin filtrul glomerular). gama globuline normale (pur), scazute (impur) si
crescute (in sindromul nefrotic din boli autoimune).
Alte teste: PT sczute
colesterol crescut (scaderea albuminelor determina cresterea sintezei de globuline decatre hepatocite, inclusiv lipoproteine => lipidele plasmatice si colesterolul, crescute insdr. nefrotic pur).
http://pro2services.com/lectures/Winter/Proteins/protein.htm
IV. MODELE PROTEICE
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Hepatita acutamodificari electroforetice
afectiune inflamatorie difuza a ficatului
poate evolua cu insuficienta hepatica acuta
PT normale.
beta globulinelecrescutecresterea IgM (pot migra i n zona alfa 2 i n beta, eventualasociate cu cresterea IgA n hepatitele alcoolice).
gama globuline crescute (policlonal).
Albuminele - pot fi sczute, n funcie de severitatea afectarii hepatice(au un turn-over de 21zile, scderea sintezei hepatice poate fi mascat de nivelul de albumine existent n momentul declanrii bolii).
Transferina (o betaglobulina) crestein hepatita acuta (in special virala)lizahepatocitara cu eliberare de fier.
IV. MODELE PROTEICE
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Hepatita cronicamodificari electroforetice
caracterizata prin infiltrare predominant portala (PMN, limfocite si plasmocite) si prindezvoltarea anormala a tesutului conjunctiv.
PT normale
beta globuline crescute
gama globuline crescute
Albuminele pot fi sczute in hepatita cronica cu insuficienta hepatica (deficit desinteza).
beta globuline sunt crescute n cazul unei hepatite cronice acutizate si ca urmare a cresteriitransferinei (leaga fierul elibeta din hepatocite).
Celelalte benzi sunt normale sau se modifica compensator.
IV. MODELE PROTEICE
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Ciroza hepaticamodificari electroforetice
Stadiul final al hepatopatiilor cronice.
Evolueaza cu fibroza, necroza hepatocitara
si noduli de regenerare.
Evolueaza cu insuficienta hepatica => deficit
de sinteza a proteinelor.
PT sczute
albumine sczute
beta globulinecrescute
gama globulinecrescute (policlonalIgG, IgA, IgM)
Ficatul nu mai poate cataboliza Ig imbatranite ; in plus, prin prezenta sunturilor porto-cave,Ig nu mai efectueaza pasajul hepatic => Ig cresc (hipergamaglobulinemie).
http://quizlet.com/18068736/protein-electrophoresis-flash-cards/
IV. MODELE PROTEICE
V PROTEINE ANORMALE
http://www.google.ro/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&docid=ylprEnG-n09OuM&tbnid=Bim8R31E2owcpM:&ved=0CAUQjRw&url=http://quizlet.com/18068736/protein-electrophoresis-flash-cards/&ei=coSIUtezBo_Lswb9noGACw&bvm=bv.56643336,d.bGE&psig=AFQjCNECa-N-kHOeaaykrD6xCJGAEvgomw&ust=1384764901294578http://www.google.ro/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&docid=U6bVFcOGNyJzFM&tbnid=qOZgOv12LOcYTM:&ved=0CAUQjRw&url=http://www.nutricionnatural.info/tipos/alfa-feto-proteina.html&ei=O4eIUsH4I8ratAb0_oG4Cg&bvm=bv.56643336,d.bGE&psig=AFQjCNGACKlVAun2U5CcEoXuXeph9uVKdA&ust=1384765611563708 -
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Alfa-1-fetoproteina (AFP)
Valori normale < 6.0 ng/mL globulina sintetizata in ficat, tractul GI, sacul vitelin; Rol:
- prezenta fiziologic: la fat, n primul an dup nateresi la femeile gravide.- marker de celule nediferentiate si arata rata de multiplicare dintr-un organ.
Indicatii pentru dozare:
suspiciune de carcinom hepatocelular;
depistarea precoce a carcinomului hepatic in ciroza hepatica;
screening-ul prenatal pentru depistarea afectiunilor de tipanencefalie, spina bifida.
Valori crescute:
- la adult- in afectiuni hepatice benigne/procese de regenerare hepatica/neoplasme;
- traverseaza placenta de la fat la mama si creste foarte mult cand exista malformatiifetale de tub digestiv si sistem nervos (spida bifida, anencefalie).
Valori scazute:
- cand nu exista celule cu rata crescuta de diviziune (sarcina molara).http://www.nutricionnatural.info/tipos/alfa-feto-proteina.html
V. PROTEINE ANORMALE
O A O A
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Antigenul carcinoembrionar (CEA)
Valori normale
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CA 15-3
- detectarea recurentei neoplasmului mamar si monitorizarea raspunsului la tratament.
CA 19-9
- diagnosticul si monitorizarea ADK pancreatic, gastric si tumorilor hepatobiliare;
- diagnosticul si monitorizarea neoplasmului colorectal (al doilea marker dupa CEA)
si ovarian (al doilea marker dupa CA 125).
CA 125
-diagnosticul, tratamentul si aprecierea prognosticului in neoplasmul ovarian.
- la pacientele cu AHC de neoplasm ovarian/mamar - determinarea CA 125 la 6 luni.
- suspiciune de adenocarcinom pancreatic (al 2-lea marker dupa CA 19-9).
V. PROTEINE ANORMALE
TEST VALOARE VARIATIE
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TEST VALOARE VARIATIEPT 12,5 g % Crescut
Albumine 35 % NormalAlfa 1 6 % Normal
Alfa 2 7 % ScazutBeta 10 % Scazut
Gama 42 % Crescut
Paraproteine in urina Lt k Crescut
TEST VALOARE VARIATIEPT 4,5 g % Scazut
Albumine 18 % ScazutAlfa 1 3 % Normale
Alfa 2 40 % CrescutBeta 19 % Crescut
Gama 20 % NormalColesterol 350 mg % Crescut
Proteinurie 5,2 g % Prezent
VSH 43mm/1h Crescut
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1. Fiziopatologie Atlas color, Stefan Silbernagl, Florian Lang, Editura Callisto, 2010.
2. Mosbys Manual of Diagnostic and Laboratory Tests, Kathleen Deska Pagana, Timothy j. Pagana,Elsevier, third edition.
3. Analize de laborator si alte explorari diagnostice, Editura MedicArt, 2007.
4. Oxford Handbook of Clinical and Laboratory Investigation, Drew Provan, Oxford University Press,
third edition, 2010.
5. Differential Diagnosis by Laboratory Medicine , a quick reference for physicians, Marks V., Cantor
Th., Mesko D., Pullman R., Nosalova Gabriela , Springer, 2002.
6. Fiziopatologie - Note de curs si lucrari practice, Daniela Adriana Ion.
7. Compendiu de fiziopatologie speciala, Badescu M., Ciocoiu M. , Editura Pim, 2001.
8. Curs de Fiziopatologie Generala , Marcela Dinu, Veronica Colev , Magda Badescu, editia a III-a,
litografia I.M.F. Iasi, 1988.
9. Pathologic basis of disease ,Cotran R.S., Kumar V., Collins T., eighth edition, Saunders Elservier,
2010.
10. Essential Pathology, Rubin E., Farber J.L., third edition. Emanuel Rubin, Lippincott Williams &
Wilkins, 2001.
11. http://www.copewithcytokines.de/cope.cgi?key=Acute%20phase%20proteins
BIBLIOGRAFIE SELECTIVA
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Multumesc pentru atentie!
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