JAUNDICE

Dr. Soegiarto Gani, SpPD

Bagian Ilmu Penyakit Dalam/ FK. USU/ RSUP. HAM

Jaundice ( ikterus ) :

-kuning pada mukosa dan kulit.

-bilirubin > 2 mg/dl atau > 34 mol/L

-terlihat pada sklera, kulit, dan dark urineeasiest to see under natural light easiest to see in sclera

Jaundice dlm darah = hiperbilirubinemia. 80–85% bilirubin dari pemecahan haemoglobin dan sekitar 15-20% dari haem erythrocyte yang matang (mature ) dan immature cell pada lien dan sumsum tulang.

Metabolisme Haemoglobin bilirubin

Sifat dan reaksi Tidak Terkonjugasi terkonjugasi

Kelarutan dalam air 0 +

Afinitas thd lemak + 0

Ekskresi renal 0 +

Reaksi van den Bergh Indirek (total) Direk (minus direk)

Ikatan dgn albumin serum +++ + (reversibel)

Pembentukan kompleks 0+† bilirubin-albumin (ireversibel)

SIFAT-SIFAT KOMPARATIF ANTARA BILIRUBIN TERKONJUGASI DAN TIDAK

TERKONJUGASI-

Jaundice

• Post Hepatic (Obstructive) – Stone, tumor– Conjugated/Direct Bil, High colored urine,

• Pre Hepatic (Acholuric) - Hemolytic– Unconjugated/Indirect Bil, pale urine

• Hepatocellular Jaundice - Viral – Liver damage - unconjugated– Swelling, canalicular obstruction - Conjugated

Bilirubin uptake

PLASMA

SINUSOIDAL MEMBRANE

CYTOSOL

ENDOPLASMIC RETICULUM

BR – albumin

BR + albumin

Carrier proteins Flip / flop

BR

Protein bound ( ligandin )

Membrane-membrane transfer

Conjugation ( UGT1)

Mono and diglucuronides

Transporters MOAT

Bile

CANALICULAR MEMBRANE

Transportase dari bilirubin

Klasifikasi

Klasifikasi jaundice menurut :

1. Unconjugated hyperbilirubinemia

2. Conjugated hyperbilirubinemia

1. Unconjugated hyperbilirubinemia

Overproduction from breakdown of haemoglobin and other heme proteins

Haemolysis (intra-and extravascular) Ineffective erythropoiesisEnhanced turnover of hepatic heme enzymes Impairment of hepatic uptake

Decreased delivery to the liverDrugs

Gilbert syndrome,type I Impairment of hepatic conjugationNeonatal

Maternal milkLucey-Driscoll syndrome

Crigler – Najjar syndrome, type I Crigler – Najjar syndrome, type II (arias syndrome)Gilbert syndrome, type II

Drugs

Conjugated hyperbilirubinemia

Defect of hepatic exretionExtrahepatic bile duct obstruction

Extrahepatic bile duct atresiaHepatic jaundiceIntrahepatic 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 cirrhosisPrimary sclerosing cholangitis (PSC)Inherited defective excretio of conjugated organic

anions and coproporphyrinDubin – johnson syndrome

Rotor syndrome

Beberapa penyebab jaundice yg sering dgn investigasinya

Penyebab Investigasi

Acute hepatitis - HBsAg, anti – HBc IgM, HBeAg, anti-Hbe- Anti-HAV IGM, Anti delta antibody- Anti HCV- Anti HEV ?- IgM-EBV, IGM-CMV, Leptospiral antibody

Pancreatic / Biliary Disease

- Ultrasonography- Endoscopic retrograde cholangiography- c Pancreatography- Percutaneuos transhepatic cholangiography- CT scan

Malignancy - Ultrasonography- CT scanning- Liver biopsy- Alpha foetoprotein

Cirrhosis - Hepatitis B/C serology- Ultrasonography- Liver biopsy- Immunoglobulins- Auto antibodies- Iron studies- serum, urine and liver copper;serum ceruloplasmin- alpha 1 antitrypsin

Haemolysis - Reticulocyte count- Haptoglobin- Direct and indirect Coombs’ Test- G-6-P-D level

Cardiorespiratory Failure

- Chest X Ray- ECG

Gilbert’s Syndrome

- Increase in unconjugated bilirubin following 2-3 days on a 400 calorie diet

Unconjungated Hyperbilirubinemia Akibat Defektive Hepatic Uptake

Jaundice

Unconjugated hyperbilirubinemia

Congestive heart failure Portal-Systemic

shunt

Drugs : Rifamycin

Bunamiodyl Probenecid flavaspidic

acid

Serum bilirubin after fasting (400 cal/3 days )

serum bilirubin after

phenobarbital Bil. kinetics : R4h>10% CBR<0.8

ml/min/kg K21 (uptake)

Normal AST/ALT, AP, -GT, BA

Decreased delivery to the liver

Competition for hepatic uptake

GILBERT syndrome

Algoritma penanganan Jaundice Uncojungated hyperbilirubinemia oleh karena over production

Uncungated hyperbilirubinemia akibat defect atau inhibisi hepatic UDP-GT

Conjugated Hyperbilirubenemia Non Cholestasis Jaundice

Conjugated hyperbilirubinemia cholestasis jaundice

Extrahepatic cholestasis

Conjugated hyperbilirubinemia akibat reversible atau progressive intra hepatic cholestasis

Consequences of Cholestasis

• Malabsorption of fat

• Essential fatty acid deficiency

• Fat soluble vitamin deficiency (A,D,E.K)

• Pruritis

• Secondary biliary cirrhosis*

• Cholangitis*

* especially seen with extrahepatic cholestasis