Approximately 80-85% of the bilirubin produced is derived from the heme moiety of the haemoglobin released from aging erythrocytes in the reticuloendothelial cells. Bilirubin, bound to albumin, is transported into the liver where it is rapidly conjugated with glucuronide to increase its solubility. Then it is excreted into biliary canaliculi, and hydrolyzed in the gastrointestinal tract.
Unconjugated bilirubin serum concentration increases in case of overproduction of bilirubin (acute or chronic haemolytic anemias)
and in case of disorders of bilirubin metabolism and transport defects (impaired uptake by liver cells: Gilbert’s syndrome; defects
in the conjugation reaction: Crigler-Najjar syndrome). Reduced excretion (hepatocellular damage: hepatitis, cirrhosis…; DubinJonhson and Rotor syndrome) and obstruction to the flow of bile (most often produced by gallstones or by tumours) induce an
important elevation of conjugated bilirubin and in a minor extent an increase of unconjugated bilirubin (conjugated hyperbilirubinemia).