Bilirubin is produced by catabolism of hemoglobin in extra-hepatic tissues. Hepatocytes conjugate the bilirubin, and it is then excreted into bile. Blood bilirubin levels are a function of production rate and biliary excretion. Total bilirubin is a combination of lipid-soluble unconjugated bilirubin and water-soluble conjugated bilirubin. Total bilirubin is less than 1.5 mg/dL and is normally primarily unconjugated bilirubin. The initial step in the evaluation of an elevated bilirubin level is to distinguish conjugated (direct) from unconjugated (indirect) hyperbilirubinemia.

Probably the most common cause of unconjugated hyperbilirubinemia is Gilbert's syndrome, a benign condition that affects up to 5% of the population. In Gilbert's syndrome, only the unconjugated bilirubin is elevated; the rest of the liver enzymes are normal. Other causes of unconjugated hyperbilirubinemia include hemolysis, ineffective erythro-poiesis (as in megaloblastic anemias), or a recent hematoma. With normal hepatic function, hemolysis is not associated with bilirubin levels greater than 5 mg/dL. In an asymptomatic person with mildly elevated unconjugated hyperbiliru-binemia (<4 mg/dL), a presumptive diagnosis of Gilbert's syndrome can be made if there are no medications that cause elevated bilirubin, there is no evidence of hemolysis, and the liver enzymes are normal (Green and Flamm, 2002).

Conjugated hyperbilirubinemia generally occurs with defects of hepatic excretion, including extrahepatic obstruction, intrahepatic cholestasis, cirrhosis, hepatitis, and toxins. Bili-rubinuria is a fairly sensitive marker for biliary obstruction and may occasionally be found before jaundice is evident.

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