Bilirubin Metabolism and Jaundice

Bilirubin, a degradation product of heme, circulates bound to albumin, from which it is extracted in the liver. It is translocated from blood to bile by a multistep process involving hepatocellular uptake, intracellular binding, conjugation with glucuronic acid, and active transport into bile. Hyperbilirubinemias are predominantly unconjugated, mainly conjugated, or mixed. Those with normal common liver function tests are often familial and benign; abnormalities of other hepatic tests suggest a condition with potentially serious sequelae. Studies of familial hyperbilirubinemias have identified specific proteins and pathways essential for normal liver function, including bilirubin transport and metabolism. Mutations in particular proteins underlie four of the five familial hyperbilirubinemias: the Gilbert, Crigler-Najjar types 1 and 2, and Dubin-Johnson syndromes. The basis for Rotor syndrome remains unknown. Many different mutations in three protein components of the canalicular bile secretory apparatus are likewise the basis for several familial cholestasis syndromes.