Bilirubin is formed in the reticuloendothelial system during the degradation of aged erythrocytes. The heme portion from hemoglobin and from other-containing proteins is removed, metabolized to bilirubin, and transported as a complex with serum albumin to the liver. This process accounts for about 80% of bilirubin formed daily. Other sources of bilirubin include the breakdown of myoglobin and cytochromes and the catabolism of immature red cells in the bone marrow.

In the liver, bilirubin is conjugated with glucuronic acid for solubilization to form conjugated or direct bilirubin for subsequent transport through the bile duct into the digestive tract where it is metabolized by bacteria to a group of products collectively known as stercobilinogen. Total bilirubin is the sum of the conjugated and unconjugated fractions. Pre-hepatic diseases or conditions such as hemolytic disease or liver diseases resulting in impaired entry, transport or conjugation within the liver cause elevation of unconjugated (indirect) bilirubin. Monitoring of bilirubin in newborns, particularly if premature, has special importance since the hepatic handling of bilirubin is immature leading to elevated unconjugated bilirubin. If not bound to albumin, unconjugated bilirubin is able to cross the blood brain barrier more easily, increasing the risk of cerebral damage.

Total bilirubin is elevated in conditions causing obstruction of the bile duct, hepatitis, cirrhosis, in hemolytic disorders and several inherited enzyme deficiencies. There is information indicating elevated levels of direct bilirubin in patients with liver or biliary tract disease, even though, total bilirubin levels are normal. Therefore, the greatest diagnostic value of direct bilirubin assays stem from their ability to indicate occult liver disease4.