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Mara Isabel Mnera Jaramillo, Jefa Laboratorio Clnico Clnica Cardiovascular Santa Mara
1 30/08/05
HGADO
Esfago Lbulo der. Lbulo izq
C. Heptico comn
2 30/08/05
Funcin heptica
Sntesis
Protenas plasmticas Lpidos endgenos y lipo-protenas Factores de coagulacin Glucgeno/glucosa
Metabolismo
Frmacos lipo-solubles Txicos
Dufour, R. Evaluation of Liver Function and Injury. In: Clinical Diagnosis and Management by Laboratory Methods, Ed 20th
3 30/08/05
Funcin heptica
Biotransformacin
Enzimtica Oxidacin Reduccin Hidrlisis Hidroxilacin Transferasas Conjugasas
Sistema Citocromo P450 (Fase I) Reacciones de sntesis (Fase II)
Conjugacin *
Funcin heptica
SRE (clulas de Kupffer) Almacena energa (glucgeno) Almacena Fe, Vit A, D y B12 rgano endocrino
Angiotensingeno Factor de crecimiento I Triyodotironina PTH Insulina Estrgenos Cortisol
Depuracin de hormonas
5 30/08/05
Determinar presencia o no de enfermedad heptica Hacer diagnstico especfico Establecer severidad Monitoreo del curso de enfermedad
6 30/08/05
Burke, MD. Liver Function: Test Selection and Interpretation of Results. Clin Lab Med 22 (2002) 377 - 390
NACB (National Academy of Clinical Biochemistry) AASLD (American Association for the Study of Liver Diseases) CMS (Centers for Medicaid Services)
Albmina Prot. totales
ALT
ALP
Bbna T
AST Bbna D
Burke, MD. Liver Function: Test Selection and Interpretation of Results. Clin Lab Med 22 (2002) 377 - 390
7 30/08/05
Tipos de Pruebas
Metabolismo aninico orgnico Bbna T y D Sntesis protenas Albmina, PT Respuesta inmune Marcadores virales Marcadores Genticos Globulina Total, Ig ANA, SMA, anti-LKM-1, AMA HAV total, HAV IgM, HBsAg, anti-HBc total, antiHBc IgM, anti-HCV, RIBA, RT-PCR Saturacin de transferrina, Ferritina, mutaciones C282Y/H63D, ndice de Fe heptico Ceruloplasmina, Cu urinario, Electroforesis, anlisis fenotpico
9 30/08/05
Burke, MD. Liver Function: Test Selection and Interpretation of Results. Clin Lab Med 22 (2002) 377 - 390
Disfuncin heptica
Necrosis celular
Aguda: Hepatitis viral, toxica, alcohlica y necrosis isqumica ( > 7 v AST/ALT)
Crnica: Hepatitis autoinmune, crnica activa, cirrosis ( < 7v AST/ALT) albmina srica
Burke, MD. Liver Function: Test Selection and Interpretation of Results. Clin Lab Med 22 (2002) 377 - 390
10 30/08/05
Disfuncin heptica
Colestasis
Intraheptica
Difusa: Inducida por frmacos, Cirrosis biliar Focal: Metstasis, granuloma, colelitiasis intraheptica * ( ALP, Bbna Normal *) ALP y Bbna)
11 30/08/05
Burke, MD. Liver Function: Test Selection and Interpretation of Results. Clin Lab Med 22 (2002) 377 - 390
Enzimas hepato-celulares
2
Alcohol
ASTm ASTm ASTc ALT ASTc GGT GGT ALT ASTc ALT ASTm
Frmacos
Necrosis celular
ASTc ALT
ASTc ASTc
Colestasis
Dufour, R. Evaluation of Liver Function and Injury. In: Clinical Diagnosis and Management by Laboratory Methods, Ed 20th
12 30/08/05
Dmero Peso molecular: 93 kDa Cofactor: Piridoxal 5-fosfato (P- 5- P) Isoenzimas mitocondrial y citoplasmtica (AST) Catabolismo heptico Vida media: AST 17 + 5 horas ALT 47 + 10 horas Variacin diurna es AST 5 10% ALT 10 30%
Estructura de AST
Diapositiva 13
( 45% en la tarde)
NACB: Laboratory Guidelines for Screening, Diagnosis and Monitoring of Hepatic Injury. 2000 13 30/08/05
Estructura de AST
Diapositiva 11
FUNCIN: Transferencia de grupos alanina y aspartato para producir cido pirvico y oxaloactico
P-5-P
14 30/08/05
ndice de masa corporal: Aumenta la concentracin de AST y ALT en 40 50% Falla renal: 12 16 22 Reduce nivel ALT
AST fem
30 ALT masc
40
50 ALT fem
60
AST masc
NACB: Laboratory Guidelines for Screening, Diagnosis and Monitoring of Hepatic Injury. 2000
15 30/08/05
Medicamentos
Acetaminofn AINES Antibiticos Inhibidores de ECA Inhibidores de hidroximetil-glutaril-CoA
Enfermedad no heptica
Sprue Hiper/hipo tiroidismo Post-colecistectoma laparoscpica
Dufour, R. Clinical Enzimology. In: Clinical Diagnosis and Management by Laboratory Methods, Ed 20th
16 30/08/05
CK
10 1700
15
500
0
17 30/08/05
Dufour, R. Clinical Enzimology. In: Clinical Diagnosis and Management by Laboratory Methods, Ed 20th
18 30/08/05
Indicadores de colestasis
Incremento en enzimas canaliculares GGT ALP Incremento de Bbna Incremento del colesterol AMA, p-ANCA
19 30/08/05
Burke, MD. Liver Function: Test Selection and Interpretation of Results. Clin Lab Med 22 (2002) 377 - 390
Patrones de colestasis
Tipo
Bilirrubinostasis
ALT N
ALP N
BBNA
Ejemplos
Sepsis, TPN, esteroides sexuales Frmacos, Dficit -1 anti-tripsina Cirrosis biliar 1a. Colangitis esclerosante 1a. Clculos CB Ca pncreas
N/
N/
Obstruccin completa
Dufour, R. Evaluation of Liver Function and Injury. In: Clinical Diagnosis and Management by Laboratory Methods, Ed 20th
20 30/08/05
Indicadores de colestasis
Actividad osteoblstica *
Burke, MD. Liver Function: Test Selection and Interpretation of Results. Clin Lab Med 22 (2002) 377 - 390
21 30/08/05
Indicadores de colestasis
Dufour, R. Clinical Enzimology. In: Clinical Diagnosis and Management by Laboratory Methods, Ed 20th
22 30/08/05
Indicadores de colestasis
estrustura
Dufour, R. Clinical Enzimology. In: Clinical Diagnosis and Management by Laboratory Methods, Ed 20th
23 30/08/05
Placenta Hgado
Hueso Intestino
Minutos 1 da 3 das 7 das
24 30/08/05
Dufour, R. Clinical Enzimology. In: Clinical Diagnosis and Management by Laboratory Methods, Ed 20th
Regresa Alkaline Phosphatasa Activity as a Clinical Chemistry Diagnostic Aid. 2004 WWW.vet.uga.edu/vpp/CLERK/raymond
25 30/08/05
Indicadores, colestasis
Dufour, R. Clinical Enzimology. In: Clinical Diagnosis and Management by Laboratory Methods, Ed 20th
26 30/08/05
Indicadores, colestasis
NACB: Laboratory Guidelines for Screening, Diagnosis and Monitoring of Hepatic Injury. 2000
27 30/08/05
Indicadores de colestasis
Gama glutamil transferasa - GGT
Cataliza transferencia de la porcin Gama glutamil de un pptido. Asociada a membrana plasmstica
Hepatocitos (borde canalicular) Tbulos renales proximales Clulas epiteliales intestinales Prstata
Indicadores de colestasis
GGT Variacin pre-analtica
Niveles relativos de enzima segn edad y gnero
1,2 1,0 0,8 0,6 0,4 0,2 0,0 8 12 16 22
30
40
50
60
Masculino
Femenino
Dufour, R. Clinical Enzimology. In: Clinical Diagnosis and Management by Laboratory Methods, Ed 20th
29 30/08/05
Indicadores de colestasis
GGT Variacin pre-analtica
Incremento de masa corporal ( 50% IMC >30) Fumar ( 10-20%) Etanol, anticonvulsivantes ( Primer trimestre embarazo ( ANOVA ( 20%) Variacin inter- diaria (10 15%) Vida media 7 -10 das (alcoholismo: 28d)
Dufour, R. Clinical Enzimology. In: Clinical Diagnosis and Management by Laboratory Methods, Ed 20th
5v) 25%)
30 30/08/05
Indicadores de colestasis
GGT: Comportamiento en diferentes desrdenes
Desorden Ca primario hgado Metstasis Cirrosis biliar primaria Hepatitis crnica Colestasis intra heptica Hepatitis alcohlica Obstruccin extra-heptica Cirrosis # ptes 27 138 26 38 46 144 41 136 % GGT
anormal
GGT media
(x URL)
Dufour, R. Clinical Enzimology. In: Clinical Diagnosis and Management by Laboratory Methods, Ed 20th
31 30/08/05
Bbna directa representa el 20% del total Bbna T y D aumentan en necrosis y colestasis En obstruccin extra heptica Bbna D < 25 mg/dl Incremento en Bbna T con fraccin de Bbna D < 20% Hemlisis o S. Gilbert.
Burke, MD. Liver Function: Test Selection and Interpretation of Results. Clin Lab Med 22 (2002) 377 - 390
32 30/08/05
33 30/08/05
Hiper bilirrubinemia
Causas Formacin Transporte Metabolismo Excrecin
Localizacin Aumento produccin No conjugada Alteracin Captacin/almacenamiento S. colestsicos Heredados Disfuncin hepato-celular Lesin epitelio biliar Colestasis intra-heptica Miscelneas Obstruccin biliar Causa Anemia/Reaccin hemoltica, hematoma, infarto pulmonar Post-hepatitis, S. Gilbert, S. Crigler-Najjar, Frmacos S Dubin-Johnson S. Rotor
Hiper bilirrubinemia
Conjugada
Hepatitis, cirrosis heptica Frmacos, cirrosis biliar, sepsis, ictericia postqrca. Espiroquetas, mononucleosis, colangitis, sarcoidosis, linfomas, toxinas Coledocolitiasis, atresia biliar, carcinoma conducto biliar, colangitis esclerosante, quiste del coldoco, presin externa sobre el conducto, pancreatitis, Ca pncreas 34 30/08/05
Friedman, LS. Liver, Biliary Tract, & Pancreas. In: Current Medical Diagnosis & Treatment, 2005
Efecto
NACB: Laboratory Guidelines for Screening, Diagnosis and Monitoring of Hepatic Injury. 2000
20
Masculino
40
Femenino
60
NACB: Laboratory Guidelines for Screening, Diagnosis and Monitoring of Hepatic Injury. 2000
36 30/08/05
Sntesis de protenas
Albmina
Sintetizada en hgado Vida media 21 das Reduccin indica enfermedad crnica Incremento indica hemo-concentracin
Burke, MD. Liver Function: Test Selection and Interpretation of Results. Clin Lab Med 22 (2002) 377 - 390
37 30/08/05
Sntesis de protenas
Tiempo de Protrombina
Factores I, II, V, VII y X Sintetizados en hgado II, VII y X vit K dependientes TP prolongado
Ausencia de vit K No absorcin No sntesis
Respuesta inmune
Inmunoglobulinas y anticuerpos tisulares
Incremento en Igs enfermedad heptica crnica activa o para-protenas Posible hepatitis auto inmune
IgM AC anti-mitocondriales
39 30/08/05
Gua de interpretacin
Protenas Totales Albmina AST - - - - - - - ALT - - - - - - AST:ALT <1 >2 <1 - 1 >1 ALP Bbna T - - - - - - Bbna D - - - - - -
Desorden Hepatitis aguda H. alcohlica aguda H. crnica Enf alcohlica crnica Colestasis intra heptica difusa Obstruccin extra heptica Enf. Intra heptica focal
- -
- -
- - - -
- - -
- - -
- - -
1 1
-
40 30/08/05
Burke, MD. Liver Function: Test Selection and Interpretation of Results. Clin Lab Med 22 (2002) 377 - 390
SI
ALB Glob
NO
SI
NO
Necrosis crnica activa
NO
Necrosis Aguda inflamacin crnica
SI
SI
NO NO
SI
NO
SI
LDH/AST > 2
NO
SI SI
NO
SI NO SI
Hepatopata alcohlica
NO
Frmacos colestsicos
NO
SI
Colestasis Intra hep.
Hepatopata NO Probable
SI
NO
NO
Metstasis
SI
Enf. hipxica Colestasis Alcohlica aguda Colestasis de causa desconocida
42 30/08/05
GRACIAS
43 30/08/05