Clinical Information

Bilirubin is a degradation product of hemoglobin. Red blood cells at the end of their circulating lives are broken down in the reticuloendothelial system, mainly the spleen. The resulting heme is converted to bilirubin upon removal of iron. 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 blood cells in the bone marrow. Once formed, bilirubin is transported to the liver bound to albumin. Bilirubin bound to albumin is insoluble in water and is known as unconjugated (indirect) bilirubin. In the liver, unconjugated bilirubin is coupled with glucuronide; this form is called conjugated (direct) bilirubin. It is water soluble and is mostly excreted in bile.

The sum of direct and indirect bilirubin is called total bilirubin and the indirect fraction of the total usually makes up to approximately 85%. In cases of hyperbilirubinemia, bile pigment is deposited in the skin, sclera, and mucous membranes and so the patient has yellowish color; this condition is called jaundice or icterus. In newborns or in people with familial hyperbilirubinemia the presence of jaundice and elevation of total bilirubin may indicate inherited metabolic disorders.

Fractionation of total bilirubin into conjugated and unconjugated may help in the diagnosis of hyperbilirubinemia. For example, conjugated bilirubin is increased in cases of cholestasis caused by several liver diseases (e.g., hepatitis, hepatic obstruction, and cirrhosis), while a high level of unconjugated bilirubin may indicate a hemolytic disorder. Inherited metabolic disorders may also have differences in conjugated and unconjugated fractions: increased conjugated bilirubin suggests Dubin-Johnson or Rotor syndromes, while unconjugated bilirubin is prevalent in Gilbert, Crigler-Najjar, or Lucey-Driscoll syndromes. The total bilirubin test is used as an aid in the differential diagnosis and management of liver diseases, and neonatal jaundice, as well as hemolytic, and inherited metabolic diseases.

Neonatal bilirubin quantitation is also used to monitor diseases causing jaundice in the newborn, chiefly erythroblastosis fetalis (also called hemolytic disease of the newborn or HDN). HDN is caused by maternal alloimmunization to RhD, antibodies involving additional blood groups, and ABO incompatibility. The average full-term newborn infant has a peak serum bilirubin concentration of 5 to 6 mg/dL. Physiologic jaundice is seen at serum bilirubin concentrations from 7 to 17 mg/dL. Serum bilirubin concentrations greater than 17 mg/dL may be pathologic. The primary concern is the potential for bilirubin encephalopathy or severe jaundice.