Faculdade de Cincias Mdicas Hospital Egas Moniz CHLO - EPE

ndice
Definio Diagnstico diferencial Metabolismo da bilirrubina Classificao e caracterizao da ictercia 0 Abordagem ao doente
0 0 0 0
0 Histria Clnica 0 Exame Objectivo 0 Exames complementares

0 Bibliografia

de diagnstico 0 Medio da bilirrubina srica 0 Algoritmo

Definio
0 A ictercia corresponde a uma descolorao dos tecidos, que causada pela deposio de bilirrubina ( 3,0 mg/dl).

Definio
Esclertica Locais de deposio Mucosas (sublingual e palato duro) Pele

Diagnstico diferencial
Carotenoderma Pigmento acumula-se nas palmas, plantas, fronte e comissura nasolabial Utilizao de quinacrina Pele Exposio excessiva a fenis

Metabolismo da bilirrubina
1) 4) 2)

3)

Classificao da ictercia
0A

ictercia pode ter diferentes classificaes de acordo com:

1. 2. 3.

Origem Mecanismo Padro de hiperbilirrubinmia

Classificao da ictercia
1. Origem

0 Pr-heptica 0 Heptica 0 Ps-heptica

Classificao da ictercia
2. Mecanismo 0 Aumento da produo de bilirrubina
0 Hemlise ou eritropoiese ineficaz 0 Reabsoro de sangue

0 Diminuio

da

clearance

de

bilirrubina
0 Alteraes metablicas especficas 0 Sndrome de Crigler-Najal e de

Gilbert 0 Colesttica

0 Intra-heptica (hepatite, cirrose, spsis, medicao, destruio dos canais biliares) 0 Extra-heptica (clculos, tumores, estenoses, pancreatites)

Classificao da ictercia
3. Padro de hiperbilirrubinmia

0 No-conjugada

0 Conjugada

PrPr-heptica

Hemlise e turnover de hemoprotenas Formao da Bnc

Heme -> Biliverdina -> Bnc Bnc + albumina

Distrbios Hemolticos - Hereditrios - Adquiridos

Distrbios hemolticos
Hereditrios
Esferocitose Anemia falciforme Talassmia Deficincias em enzimas eritrocitrias

Adquiridos
Anemia hemoltica microangioptica Hemoglobinria paroxstica nocturna Spur cell anemia Hemlise imune Eritropoiese ineficaz

Os distrbios hemolticos causam hiperbilirrubinmia isolada! No hemograma h apenas aumento da bilirrubina noconjugada!

PrPr-heptica

Hemlise e turnover de hemoprotenas Formao da Bnc Captao

Heme -> Biliverdina -> Bnc Bnc + albumina

Distrbios Hemolticos - Hereditrios - Adquiridos - Frmacos

Bnc + ligandina Bnc + ac. glicurnico

Bilirrubina UDPGT

Heptica

Conjugao

- S. Crigler Najjar - S. Gilbert - Hiperbilirrubinmia Neonatal

Bc

Sais Biliares

- S. Dubin-Johnson -S. Rotor - Danos dos hepatcitos

Secreo

Frmacos
0 Rifampicina 0 Probenecid 0 Ribavirina

Deficincias na Bilirrubina UDPGT

0 Sndrome de Crigler-Najjar
0 tipo I 20-45 mg/dl 0 tipo II 6-25 mg/dl

0 Sndrome de Gilbert - < 6mg/dl 0 Hiperbilirrubinmia neonatal -

20 mg/dl

Deficincias na secreo
0 Sndrome de Dubin-Johnson 0 Sndrome de Rotor

Outras causas de ictercia heptica

0 Hepatites virais e auto-imunes 0 Doena heptica alcolica 0 Toxinas ambientais 0 Doena de Wilson

Outras causas de ictercia heptica

Padro Hepato-Celular

Alterao das enzimas AST e ALT

FA ligeiramente

Hepatite Viral
0 Fases: 0 Incubao

- Assintomtica - Aguda - Crnica

ou prodrmica

0 Pr-ictrica sintomtica 0 Ictrica sintomtica 0 Convalescena

ALT > 2 AST

Hepatite Viral
Pr-ictrica Sintomtica

Incubao

0 Mal-estar 0 Fadiga 0 Nusas 0 Hiporexia 0 Febrculas 0 Mialgia 0 Diarria 0 Cefaleia

Convalescncia
0 Fadiga 0 Debilidade Muscular

Ictrica

Hepatite Viral
HEPATITE Vrus Genoma Transmisso A HAV RNA FecalFecal-oral B HBV DNA Parenteral Sexual Vertical 30-180 30HBsAg HBcAg HBeAg Anti-HBs AntiAntiAnti-HBc AntiAnti-HBe 1-4% Sim Sim C HCV RNA Parenteral Sexual Vertical 20-90 20----AntiAnti-HCV Anti-HDV AntiAnti-HEV AntiD HDV RNA Parenteral Sexual Vertical 30-50 30HDVHDV-Ag E HEV RNA FecalFecal-oral

Perodo de incubao Antgeno

1515-45 HAVHAV-Ag

15-60 15HEV-Ag HEV-

Anticorpo

AntiAnti-HAV

Hep. Fulminante Cronicidade Carc. Hepatocelular

0,10,1-0,4% No Nao

Rara Sim Sim

3-4% (co-infeco) (coSim No h aumento

0,3-3% 0,3No No

Hepatite Viral

Doena Heptica Alcolica

Doena Heptica Alcolica

Clnica
- Hepatomeglia - Dor Abdominal - Nuseas - Ictercia - Febre - Telangiectasias ( aranhas vasculares ) - Ascite - Edemas dos membros inferiores - Circulao Venosa Superficial - Ginecomastia - Estrias ungueais - Contractura de Dupuytren - Flapping - Diminuio da pilosidade - Atrofia testicular - Encefalopatia Heptica - Fadiga

Padro das aminotransferases

AST > 2 ALT

Toxinas Ambientais

Cloreto de Vinil

Ch da Jamaica (Alcalides Pirrolizidnicos)

CavaCava-Cava

Amanita phalloides
(Amatoxinas)

Doena de Wilson
- Doena hereditria AR - Gene ATP7B - Acumulao txica de Cu

Importncia do rastreio em jovens com cirrose

Doena de Wilson

PrPr-heptica

Hemlise e turnover de hemoprotenas Formao da Bnc Captao

Heme -> Biliverdina -> Bnc Bnc + albumina

Distrbios Hemolticos - Hereditrios - Adquiridos - Frmacos

Bnc + ligandina Bnc + ac. glicurnico

Bilirrubina UDPGT

Heptica

Conjugao

- S. Crigler Najjar - S. Gilbert - Hiperbilirrubinmia Neonatal

Bc

Sais Biliares

- S. Dubin-Johnson -S. Rotor -Danos nos hepatcitos Desordens Colestticas - Intra-hepticas - Extra-hepticas

Secreo

PsPs-heptica

Blis

Glomrulos 10-20% Renais Sangue Venoso Portal

Transporte

Bc

Urobilinognio Fezes 80%

Cholestatic Disorders
Liver functional alterations suggestive of Cholestasis GGT ALP

Ultrasound Test

I.Unexpensive II.Does not expose the patient to ionizing radiation III.High Sensibility and Specificity

Ultrasound Test

Biliary Dilatation

ABSENCE

PRESENCE

Intrahepatic cholestasis
N.B.

Extrahepatic cholestasis

False-negative results occur in patients with partial obstruction of the common bile duct or in patients with cirrhosis or primary sclerosing cholangitis (PSC) where scarring prevents the intrahepatic ducts from dilating

Intrahepatic cholestasis
A. Viral hepatitis 1. Fibrosing cholestatic hepatitis hepatitis B and C 2. Hepatitis A, Epstein-Barr virus, cytomegalovirus B. Alcoholic hepatitis C. Drug toxicity 1. Pure cholestasis anabolic and contraceptive steroids 2. Cholestatic hepatitis chlorpromazine, erythromycin estolate 3. Chronic cholestasis chlorpromazine and prochlorperazine D. Primary biliary cirrhosis E. Primary sclerosing cholangitis F. Vanishing bile duct syndrome 1. Chronic rejection of liver transplants 2. Sarcoidosis 3. Drugs G. Inherited H. Cholestasis of pregnancy I. Total parenteral nutrition J. Nonhepatobiliary sepsis K. Benign postoperative cholestasis L. Paraneoplastic syndrome M. Venoocclusive disease N. Graft-versus-host disease O. Infiltrative disease (TB, Lymphoma, Amyloid)

Drug-induced cholestasis
0 Variant of drug-induced hepatitis 0 Usually reversible after eliminating the offending drug
N.B. !! It may take months for cholestasis to resolve

ASSOCIATED DRUGS Anabolic and contraceptive steroids (most common cause!!) Chlorpromazine Imipramine Tolbutamide Sulindac Cimetidine Erythromycin estolate Bactrim Penicillin-based antibiotics

Auto-immune hepatitis with biliar target

Primay biliary cirrhosis
0 Middle-aged women 0 Progressive destruction of interlobular bile ducts 0 95% Anti-mithocondrial AB (DIAGNOSTIC)

Primary sclerosing cholangitis

Destruction and fibrosis of larger bile ducts Intrahepatic duts may be involved (with associated intrahepatic cholestasis) Diagnosis with biliar tree imaging (multiple strictures with proximal dilatation) ALWAYS search for IBD (75% associated) Remember:may be associated with Cholangiocarcinoma

Intrahepatic cholestasis: other causes

0 Vanishing bile duct syndrome 0 Adult bile ductopenia
Rare conditions Biopsy: number of bile ducts Patients with chronic transplant rejection or GVHD after bone marrow transplant

Familiar forms Progressive familiar intrahepatic cholestasis Benign recurrent cholestasis Others
Total parenteral nutrition Nonhepatobiliar sepsis Benigne postoperative cholestasis Paraneoplastic Syndromes (e.g. Stauffer s syndrome)

Extrahepatic cholestasis
Benign
Choledocholithiasis Post-operative Primary sclerosis cholangitis Cronic pancreatitis AIDS Cholangiopaty Mirizzi s Syndrome Parasite infection (Ascaridiase)

Malign
Pancreatic Carcinoma Gallbladder Carcinoma Ampullary Carcinoma Cholangiocarcinoma

Choledocholithiasis
0 Most common cause 0 Many different clinical presentations (position, timing of the obstruction)
Discomfort (upper right quadrant) Ascending cholangitis Variable elevation of the enzyme tests Jaundice, sepsis, and circulatory collapse

AIDS Cholangiopaty
Due to bile duct infection with CMV or Cryptosporidia (N.B. cholangiographic appearance similar to that of PSC) ALP, Bilirubin remains normal no jaundice!

Extrahepatic cholestasis

PrPr-heptica

Hemlise e turnover de hemoprotenas Formao da Bnc Captao

Heme -> Biliverdina -> Bnc Bnc + albumina

Distrbios Hemolticos - Hereditrios - Adquiridos - Frmacos

Bnc + ligandina Bnc + ac. glicurnico

Bilirrubina UDPGT

Heptica

Conjugao

Bc

Sais Biliares

- S. Crigler Najjar - S. Gilbert - Hiperbilirrubinmia Neonatal - S. Dubin-Johnson - S. Rotor

Secreo

PsPs-heptica

Blis

Glomrulos 10-20% Renais Sangue Venoso Portal

Desordens Colestticas - Intra-hepticas - Extra-hepticas

Transporte

Bc

Urobilinognio Fezes 80%

Abordagem ao doente
I. Histria Clnica
0 Sintomas 0 Febre 0 Mal estar 0 Perda de peso 0 Prurido 0 Sinais 0 Alterao da colorao das esclerticas, mucosas e pele 0 Cor da urina cor do vinho do Porto, coca-cola ou ch 0 Cor das fezes aclicas, hipoclicas ou hiperclicas

Abordagem ao doente
I. Histria Clnica
0 Antecedentes pessoais e scio-culturais 0 Pas de origem 0 Histria familiar 0 Consumo de lcool 0 Consumo de marisco 0 Actividade sexual 0 Transfuses 0 Medicao 0 Drogas 0 Viagens

Abordagem ao doente
I. Histria Clnica
Ictercia prheptica Antecedentes familiares Medicao Ocupao Contacto com ictercia Viagens lcool Actividade sexual Medicao Exposio ambiental Episdios prvios de ictercia Infeco Sintomas gripais Erupes Dores articulares Transfuses de sangue Medicao Viagens Dor aguda abdominal Incio insidioso de ictercia indolor

Ictercia heptica

Ictercia psheptica

Abordagem ao doente
II. Objective Exam
0 General conditions
0 Nutritional status 0 Sclerae 0 Vital signs
0 Blood pressure 0 Temperature 0 Heart Rate

0 Head/Jugular region exam

0 Keyser-Flescher Ring 0 Jugular vein examination 0 0 0 0

0 Abdominal exam

Liver and Spleen examination Superficial venous circulation Presence of Ascites Position of the umbilicus

Stigmata of chronic liver disease

0 Skin alterations
0 Color 0 Palmar erythema 0 Telangectasies 0 Xanthelasmas 0 Ecchymosis 0 Petechiae 0 Purpura

0 Duputryen Contracture 0 Gynecomastia 0 Encefalopatia 0 Atrofia testicular Laennec Cyrrose (alcoholic) 0 Arthralgia 0 Muscle pain 0 Peripheral edema

0 Jugular engorgement 0 Ascites 0 Caput Medusae 0 Hepatomegaly 0 Splenomegaly

Warning signs
0 Murphy s sign Litase 0 Courvoisier/Terrier sign Biliar estenose 0 Cullen s sign 0 Turner s sign 0 Virchow s Lymph Node 0 Sister Mary Joseph s Lymph Node

Pancreatic Carcinoma

Abordagem ao doente
III. Exames complementares de diagnstico
0 Hemograma 0 Funo heptica 0 AST, ALT e ALP (ratio AST:ALT) 0 Bilirrubina 0 -GT 0 Fosfatase alcalina 0 Albumina 0 Tempo de protrombina 0 Velocidade de sedimentao 0 PCR 0 Testes virais (HAV, HBV e HCV) 0 Ecografia abdominal 0 TC 0 MRCP 0 ERCP 0 Bipsia

Medio da bilirrubina srica

0 Reaco de van der Bergh

Bilirrubina Conjugada

Bilirrubina TOTAL Bilirrubina DIRECTA = BILIRRUBINA INDIRECTA

Bilirrubina No-Conjugada

Abordagem ao doente
IV. Algoritmo

Bibliografia
0 BRAUNWALD, Eugene, et al, Harrison s

Principles of Internal Medicine, 18th edition, McGrawHill, USA, 2011 0 Kumar and Clark s Clinical Medicine, USA 0 LONGMORE, Murray, et al, Oxford Handbook of Clinical Medicine, 6th edition, Oxford University Press, 2004 0 SOARES, Ducla, Semiologia Mdica Princpios, Mtodos e Interpretao, Lidel, Portugal