Bilirubin is a degradation product of the pigmented heme portion of hemoglobin. Old, damaged, and abnormal erythrocytes are removed from the circulation by the spleen and to some extent by the liver and bone marrow. The heme component of the red blood cells is oxidized to bilirubin by the reticuloendothelial cells and released into the blood.

In the blood, the fat-soluble bilirubin binds to albumin as unconjugated (prehepatic) bilirubin for transport to the liver. In the liver, hepatocytes detach bilirubin from albumin and conjugate it with glucuronic acid, which renders the bilirubin water soluble. Most of the conjugated (posthepatic) bilirubin is excreted into the hepatic ducts and then into bile. Only small amounts of conjugated bilirubin diffuse from the liver back into the blood. Thus, most circulating bilirubin is normally in the unconjugated form.

Bilirubin is an excretory product that serves no physiological function in bile or blood. Once the conjugated bilirubin in bile enters the intestine, most is converted to a series of urobilinogen compounds and excreted into the stool as stercobilinogen after oxidation. A lesser amount is recycled to the liver and either returned to bile or excreted in urine as urobilinogen, which is oxidized to urobilin.

Bilirubin and its degradation products are pigments and provide the yellow tinge in normal serum, the yellow-green hue in bile, the brown in stools, and the yellow in urine. Abnormally elevated serum bilirubin levels produce jaundice; obstruction to biliary excretion of bilirubin may produce light-colored stools and dark urine.

The terms indirect and direct, which are used to describe unconjugated (prehepatic) and conjugated (posthepatic) bilirubin, respectively, derive from the methods of testing for their presence in serum. Conjugated bilirubin is described as direct (direct reacting) because it is water soluble and can be measured without modification. Unconjugated bilirubin must be rendered soluble with alcohol or other solvents before the test can be performed and is thus referred to as indirect (indirect reacting).

Impaired liver function causes dramatic increases in serum bilirubin levels (hyperbilirubinemia). Bilirubin must be in the conjugated form for normal excretion via bile, stools, and urine. When the liver is unable to conjugate bilirubin adequately, serum levels of unconjugated bilirubin rise. Disorders in which excessive hemolysis of red blood cells is combined with impaired liver function also produce hyperbilirubinemia. An example is physiological jaundice of the newborn, in which the increased destruction of red blood cells, common after birth, is combined with the immature liver's inability to conjugate sufficient bilirubin. Kernicterus, a complication of newborn hyperbilirubinemia, occurs when unconjugated bilirubin is deposited in brain tissue.

Impaired excretion of conjugated (posthepatic, direct) bilirubin from the liver into the bile ducts or from the biliary tract itself causes this form of bilirubin to be reabsorbed from the liver into the blood, with resultant elevated serum levels. Because conjugated bilirubin is water soluble and readily crosses the renal glomerulus, excessive amounts may be excreted in the urine. The stools, however, are lighter in color because of diminished amounts of conjugated bilirubin in the gut.

Serum bilirubin levels are measured as total bilirubin, indirect bilirubin, and direct bilirubin. Total bilirubin reflects the combination of unconjugated and conjugated bilirubin in the serum and can be used to screen clients for possible disorders involving bilirubin production and excretion. If total bilirubin is normal, the levels of indirect (unconjugated) and direct (conjugated) bilirubin also are assumed to be normal in most cases.

When total bilirubin levels are elevated, indirect and direct bilirubin levels are measured to determine the source of the overall elevation. Specific causes of elevations in indirect and direct bilirubin are shown in Table 5-16. Numerous drugs also may alter bilirubin levels.

• Prolonged exposure of the client, as well as of the blood sample, to sunlight and ultraviolet light reduces serum bilirubin levels.
• Failure of the client to follow dietary restrictions before the test.
• Fasting normally lowers indirect bilirubin levels.
• In Gilbert's syndrome, a congenital defect in bilirubin degradation, chronically elevated levels of indirect bilirubin increase dramatically in the fasting state.
• Numerous drugs may elevate bilirubin levels (e.g., steroids, sulfonamides, sulfonylureas, barbiturates, antineoplastic agents, propylthiouracil, allopurinol, antibiotics, gallbladder dyes, caffeine, theophylline, indomethacin, and any drugs that are considered hepatotoxic); it is recommended that such drugs be withheld for 24 hours before the test, if possible.

• Known or suspected hemolytic disorders, including transfusion reactions, as indicated by elevated total and indirect bilirubin levels (see also Table 5-16):
  • Hemolysis alone rarely causes indirect bilirubin levels higher than 4 or 5 mg/dL.
  • If hemolysis is combined with impaired or immature liver function, levels may rise more dramatically.
• Confirmation of observed jaundice:
  • Jaundice manifests when serum levels of indirect or direct bilirubin reach 2 to 4 mg/dL.
• Determination of the cause of jaundice (e.g., liver dysfunction, hepatitis, biliary obstruction, carcinoma)
• Support for diagnosing liver dysfunction as evidenced by elevated direct and total bilirubin levels or by elevation of all three levels if bile duct drainage also is impaired
• Support for diagnosing biliary tract obstruction as evidenced by elevated direct and total bilirubin levels or by elevation of all three levels if liver function is impaired²⁵

Nursing Care Before the Procedure

General client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I).

• For these tests, the client should fast from foods for at least 4 hours before the test.
• Water is not restricted.
• Because many drugs may alter bilirubin levels (see section titled "Interfering Factors"), a medication history should be obtained.
• It is recommended that those drugs that may alter test results be withheld for 24 hours before the test, although this practice should be confirmed with the person ordering the study.

A venipuncture is performed and the sample obtained in a red-topped tube. The sample should be handled gently to avoid hemolysis and sent immediately to the laboratory. The sample should not be exposed for prolonged periods to sunlight (i.e., more than 1 hour), ultraviolet light, or fluorescent lights. In infants, a capillary sample is obtained by heelstick.

Nursing Care After the Procedure

Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample.

• Resume food and any drugs withheld before the test.
• Abnormal values: Note and report increased levels. Assess for associated signs and symptoms of hyperbilirubinemia such as jaundice, pruritus, pain caused by liver disease, biliary obstruction, or food intolerances. Administer phenobarbital if levels are greater than 12 mg/dL in newborns, because this can lead to central nervous system damage. Prepare for exchange transfusion if level is greater than 15 mg/dL.