Indirect (or unconjugated) bilirubin is formed by the breakdown of hemoglobin in the red blood cells. The liver converts this bilirubin into direct bilirubin, which can then be released into the intestine by the gallbladder for elimination. Total bilirubin levels are therefore indicative of both the destruction of red blood cells and the proper functioning of the liver, gallbladder, and bile ducts.
A high level of total bilirubin (hyperbilirubinemia), caused mainly by an increase in the indirect portion, can signal a problem in the hemolysis (breakdown) of red blood cells (several causes), a post-blood transfusion reaction, or cirrhosis of the liver. Slightly elevated levels (less than 80 micromoles per litre) are seen in Gilbert’s syndrome, a harmless and fairly common genetic condition characterized by low levels of the liver enzymes that are responsible for converting indirect bilirubin to direct bilirubin.
High bilirubin levels with the direct portion higher than the indirect portion are seen in the different types of viral hepatitis, secondary reactions to several medications, and alcohol-induced liver disease. A liver stone or gallstone, or obstruction of the bile ducts by a tumour may also be involved.