JAUNDICE

Dr. Rudi Mahruzar Lubis

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 scleraJaundice dlm darah = hiperbilirubinemia. 8085% 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 reaksiTidak Terkonjugasiterkonjugasi

Kelarutan dalam air 0+Afinitas thd lemak+0Ekskresi renal0+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-

JaundicePost Hepatic (Obstructive) Stone, tumorConjugated/Direct Bil, High colored urine, Pre Hepatic (Acholuric) - HemolyticUnconjugated/Indirect Bil, pale urineHepatocellular Jaundice - Viral Liver damage - unconjugatedSwelling, canalicular obstruction - Conjugated

Bilirubin uptake PLASMASINUSOIDAL MEMBRANECYTOSOLENDOPLASMIC RETICULUMBR albuminBR + albuminCarrier proteinsFlip / flopBRProtein bound ( ligandin )Membrane-membrane transferConjugation ( UGT1 )Mono and diglucuronidesTransporters MOATBileCANALICULAR MEMBRANE

Transportase dari bilirubin

Klasifikasi

Klasifikasi jaundice menurut :1. Unconjugated hyperbilirubinemia2. Conjugated hyperbilirubinemia1. Unconjugated hyperbilirubinemiaOverproduction from breakdown of haemoglobin and other heme proteinsHaemolysis (intra-and extravascular)Ineffective erythropoiesisEnhanced turnover of hepatic heme enzymes Impairment of hepatic uptakeDecreased delivery to the liverDrugsGilbert syndrome,type I Impairment of hepatic conjugationNeonatalMaternal milkLucey-Driscoll syndromeCrigler Najjar syndrome, type ICrigler Najjar syndrome, type II (arias syndrome)Gilbert syndrome, type IIDrugs

Conjugated hyperbilirubinemiaDefect of hepatic exretionExtrahepatic bile duct obstructionExtrahepatic bile duct atresiaHepatic jaundiceIntrahepatic reversible cholestatisfamilial recurrent cholestatis ( Summerskill -Walshe syndrome)Recurrent cholestatis of pregnancyIntrahepatic progressive cholestatisInfancy progressive cholestatis (Byler syndrome)Arteriohepatic dysplasia (Alagille syndrome)Primary biliary cirrhosisPrimary sclerosing cholangitis (PSC)Inherited defective excretio of conjugated organic anions and coproporphyrinDubin johnson syndromeRotor syndrome

Beberapa penyebab jaundice yg sering dgn investigasinya

PenyebabInvestigasiAcute hepatitis HBsAg, anti HBc IgM, HBeAg, anti-Hbe Anti-HAV IGM, Anti delta antibody Anti HCV Anti HEV ? IgM-EBV, IGM-CMV, Leptospiral antibodyPancreatic / Biliary Disease Ultrasonography Endoscopic retrograde cholangiography- c Pancreatography Percutaneuos transhepatic cholangiography CT scanMalignancy 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 antitrypsinHaemolysis Reticulocyte count Haptoglobin Direct and indirect Coombs Test G-6-P-D levelCardiorespiratory Failure Chest X Ray ECGGilberts Syndrome Increase in unconjugated bilirubin following 2-3 days on a 400 calorie diet

Unconjungated Hyperbilirubinemia Akibat Defektive Hepatic Uptake Jaundice Unconjugated hyperbilirubinemiaCongestive 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

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 CholestasisMalabsorption of fatEssential fatty acid deficiencyFat soluble vitamin deficiency (A,D,E.K)PruritisSecondary biliary cirrhosis*Cholangitis** especially seen with extrahepatic cholestasis