Clinical Information

Bilirubin is one of the most frequently used tests to assess liver function. Approximately 85% of the total bilirubin produced is derived from the heme moiety of hemoglobin, while the remaining 15% is produced from the red blood cell precursors destroyed in the bone marrow and from the catabolism of other heme-containing proteins. After production in peripheral tissues, bilirubin is rapidly taken up by hepatocytes where it is conjugated with glucuronic acid to produce mono- and diglucuronide, which are excreted in the bile.

A number of inherited and acquired diseases affect 1 or more of the steps involved in the production, uptake, storage, metabolism, and excretion of bilirubin. Bilirubinemia is a frequent and direct result of these disturbances.

Jaundice can occur as a result of problems at each step in the metabolic pathway. Disorders may be classified as those due to increased bilirubin production (eg, hemolysis and ineffective erythropoiesis), decreased bilirubin excretion (eg, obstruction and hepatitis), and abnormal bilirubin metabolism (eg, hereditary and neonatal jaundice).

The most commonly occurring form of unconjugated hyperbilirubinemia is that seen in newborns and referred to as physiological jaundice. Elevated unconjugated bilirubin in the neonatal period may result in brain damage (kernicterus). Treatment options are phototherapy and, if severe, exchange transfusion.

The rare genetic disorders, Crigler-Najjar syndromes type I and type II, are caused by a low or absent activity of bilirubin uridine 5'-diphospho-glucuronosyltransferase. In type I, the enzyme activity is totally absent, the excretion rate of bilirubin is greatly reduced, and the serum concentration of unconjugated bilirubin is greatly increased. Patients with this disease may die in infancy owing to the development of kernicterus.

The increased production of bilirubin, that accompanies the premature breakdown of erythrocytes and ineffective erythropoiesis, results in hyperbilirubinemia in the absence of any liver abnormality.

In hepatobiliary diseases of various causes, bilirubin uptake, storage, and excretion are impaired to varying degrees. Thus, both conjugated and unconjugated bilirubin is retained, and a wide range of abnormal serum concentrations of each form of bilirubin may be observed. Both conjugated and unconjugated bilirubin are increased in hepatitis, space-occupying lesions of the liver, and obstructive lesions such as carcinoma of the head of the pancreas, common bile duct, or ampulla of Vater.