<prompt> Unconjugated hyperbilirubinemia is seen in all of the following except: March 2010Crigler Najjar SyndromePhysiological jaundiceDubin-Johnson syndromeGilbe syndrome  <response>: Ans. C: Dubin-Johnson Syndrome Dubin-Johnson syndrome is an autosomal recessive disorder that causes an increase of conjugated bilirubin without elevation of liver enzymes ALT, AST. This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile. The conjugated hyperbilirubinemia is a result of defective endogenous and exogenous transfer of anionic conjugates from hepatocytes into the bile. Pigment deposition in lysosomes causes the liver to turn black. Other causes of conjugateddirect hyperbilirubinemia: Hepatocellular diseases: - Hepatitis: Neonatal idiopathic hepatitis Viral Hepatitis B, C, TORCH infections Bacterial E. colt, urinary tract infections - Total parenteral nutrition - Hepatic ischemia post-ischemic damage - Erythroblastosis fetalis late, Inspissated Bile Syndrome Metabolic disorders: Alpha-1 antitrypsin deficiency Galactosemia, tyrosinemia, fructosemia Glycogen storage disorders Cystic fibrosis Biliary tree abnormalities: - Extrahepatic biliary atresia: In first 2 weeks, unconjugated bilirubin predominates; elevated conjugated bilirubin is late. - Paucity of bile ducts - Choledochal cyst - Bile plug syndrome Causes of unconjugatedindirect hyperbilirubinemia: Increased lysis of RBCs i.e., increased hemoglobin release - Isoimmunization blood group incompatibility: Rh, ABO and minor blood groups - RBC enzyme defects e.g., G6PD deficiency, pyruvate kinase deficiency - RBC structural abnormalities hereditary spherocytosis, elliptocytosis - Infection sepsis, urinary tract infections - Sequestered blood e.g., cephalohematoma, bruising, intracranial hemorrhage - Neonatal Jaundice - Polycythemia - Shoened life span of fetal RBCs Decreased hepatic uptake and conjugation of bilirubin - Immature glucuronyl transferase activity in all newborns: term infants have 1 of adult activity, preterm infants have 0.1. - Gilbe Syndrome - Crigler Najjar Syndrome Non-hemolytic Unconjugated Hyperbilirubinemia: inherited conjugation defect very rare - Breastmilk Jaundice pregnanediol inhibits glucuronyl transferase activity Increased enterohepatic reabsorption - Breastfeeding jaundice due to dehydration from inadequate milk supply 