JAUNDICE

Dr.LEONARDO B DAIRY, SpPD-KGEH

Divisi Gastroentero-Hepatologi Bagian Ilmu Penyakit Dalam/ FK. USU/ RSUP. HAM

Jaundice ( ikterus ) :
warna kuning pada mukosa, selaput lendir, dan kulit. bila kadar bilirubin diatas 2 mg/dl atau > 34 mol/L terlihat pada sklera, kulit, dan dark urine Jaundice dlm darah (hiperbilirubinemia ). 8085% bilirubin dihasilkan oleh pemecahan haemoglobin dan sekitar 15-20% dari haem erythrocyte yang matang (mature ) dan immature cell pada lien dan sumsum tulang.

Metabolisme Haemoglobin

bilirubin

Metabolisme Bilirubin

Bilirubin Formation

Plasma

Hepatocyte

Bile

SIFAT-SIFAT KOMPARATIF ANTARA BILIRUBIN TERKONJUGASI DAN TIDAK TERKONJUGASI

Sifat dan reaksi Kelarutan dalam air Afinitas thd lemak Ekskresi renal Reaksi van den Bergh (minus direk) Ikatan dgn albumin serum (reversibel) Pembentukan kompleks bilirubin-albumin (ireversibel) Tidak terkonjugasi 0 + 0 Indirek (total) +++ 0 Terkonjugasi + 0 + Direk + +

Bilirubin uptake
BR albumin

PLASMA
BR + albumin Flip / flop BR Protein bound ( ligandin ) Membrane-membrane transfer

Carrier proteins

SINUSOIDAL MEMBRANE

CYTOSOL

Conjugation ( UGT1) Mono and diglucuronides Transporters MOAT Bile

ENDOPLASMIC RETICULUM

CANALICULAR MEMBRANE

Transpotase dari bilirubin

Klasifikasi

Klasifikasi jaundice. 1. Unconjugated hyperbilirubinemia 2. Conjugated hyperbilirubinemia 1. Unconjugated hyperbilirubinemia Overproduction from breakdown of haemoglobin and other heme proteins Haemolysis (intra-and extravascular) Ineffective erythropoiesis Enhanced turnover of hepatic heme enzymes Impairment of hepatic uptake Decreased delivery to the liver Drugs Gilbert syndrome,type I Impairment of hepatic conjugation Neonatal Maternal milk Lucey-Driscoll syndrome Crigler Najjar syndrome, type I Crigler Najjar syndrome, type II (arias syndrome) Gilbert syndrome, type II Drugs

2.Conjugated hyperbilirubinemia Defect of hepatic exretion Extrahepatic bile duct obstruction Extrahepatic bile duct atresia Hepatic jaundice Intrahepatic reversible cholestatis familial recurrent cholestatis ( Summerskill Walshe syndrome) Recurrent cholestatis of pregnancy Intrahepatic progressive cholestatis Infancy progressive cholestatis (Byler syndrome) Arteriohepatic dysplasia (Alagille syndrome) Primary biliary cirrhosis Primary sclerosing cholangitis (PSC) Inherited defective excretio of conjugated organic anions and coproporphyrin Dubin johnson syndrome Rotor syndrome

Beberapa penyebab jaundice yg sering dgn investigasinya

Penyebab Acute hepatitis Investigasi - HBsAg, anti HBc IgM, HBeAg, anti-Hbe - Anti-HAV IGM, Anti delta antibody - Anti HCV - Anti HEV ? - IgM-EBV, IGM-CMV, Leptospiral antibody - Ultrasonography - Endoscopic retrograde cholangiography- c Pancreatography - Percutaneuos transhepatic cholangiography - CT scan - Ultrasonography - CT scanning - Liver biopsy - Alpha foetoprotein

Pancreatic / Biliary Disease

Malignancy

Cirrhosis

Haemolysis

Cardiorespiratory Failure Gilberts Syndrome

- Hepatitis B/C serology - Ultrasonography - Liver biopsy - Immunoglobulins - Auto antibodies - Iron studies - serum, urine and liver copper;serum ceruloplasmin - alpha 1 antitrypsin - Reticulocyte count - Haptoglobin - Direct and indirect Coombs Test - G-6-P-D level - Chest X Ray - ECG - Increase in unconjugated bilirubin following 2-3 days on a 400 calorie diet

Unconjungated Hyperbilirubinemia Akibat Defektive Hepatic Uptake

Jaundice Unconjugated hyperbilirubinemia Normal AST/ALT, AP, -GT, BA Serum bilirubin after fasting (400 cal/3 days ) serum bilirubin after phenobarbital Bil. kinetics : R4h>10% CBR<0.8 ml/min/kg K21 (uptake)

Congestive heart failure Portal-Systemic shunt

Drugs : Rifamycin Bunamiodyl Probenecid flavaspidic acid

Decreased delivery to the liver

Competition for hepatic uptake

GILBERT syndrome

Algoritma penanganan Jaundice Uncojungated hyperbilirubinemia karena over production

Uncungated hyperbilirubinemia akibat defect atau inhibisi hepatic UDP-GT

Conjugated Hyperbilirubenemia Non Cholestasis Jaundice

Conjugated hyperbilirubenemia cholestasis jaundice

Conjugated hyperbilirubinemia akibat reversible atau progressive intra hepatic cholestasis

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