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Assessing liver function
Evaluating a wide range of diseases affecting the production, uptake, storage, metabolism, or excretion of bilirubin
Monitoring the efficacy of neonatal phototherapy
Bilirubin is one of the most commonly 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 RBC 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 bilirubin mono- and diglucuronide, which are then excreted in the bile.
A number of inherited and acquired diseases affect one or more of the steps involved in the production, uptake, storage, metabolism, and excretion of bilirubin. Bilirubinemia is frequently a direct result of these disturbances.
The most commonly occurring form of unconjugated hyperbilirubinemia is that seen in newborns and referred to as physiological jaundice.
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.
The rare genetic disorders, Crigler-Najjar syndromes Type I and Type II, are caused by a low or absent activity of bilirubin UDP-glucuronyl-transferase. 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.
In hepatobiliary diseases of various causes, bilirubin uptake, storage, and excretion are impaired to varying degrees. Thus, both conjugated and unconjugated bilirubin are retained and a wide range of abnormal serum concentrations of each form of bilirubin may be observed. Both conjugated and unconjugated bilirubins are increased in hepatitis and 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.
> or =12 months: 0.0-0.3 mg/dL
Reference values have not been established for patients who are <12 months of age.
<1 month: not established
1 month-17 years: < or =1.0 mg/dL
> or =18 years: < or =1.2 mg/dL
The level of bilirubinemia that results in kernicterus in a given infant is unknown. In preterm infants, the risk of a handicap increases by 30% for each 2.9 mg/dL increase of maximal total bilirubin concentration. While central nervous system damage is rare when total serum bilirubin (TSB) is <20 mg/dL, premature infants may be affected at lower levels. The decision to institute therapy is based on a number of factors including TSB, age, clinical history, physical examination, and coexisting conditions. Phototherapy typically is discontinued when TSB level reaches 14 to 15 mg/dL.
Physiologic jaundice should resolve in 5 to 10 days in full-term infants and by 14 days in preterm infants.
When any portion of the biliary tree becomes blocked, bilirubin levels will increase.
Specimens should be protected from light and analyzed as soon as possible.
Grossly hemolyzed specimens should be rejected because hemoglobin inhibits the diazo reaction and falsely decreased results may be seen.
Compounds that compete for binding sites on serum albumin contribute to lower serum bilirubin levels (eg, penicillin, sulfisoxazole, acetylsalicylic acid).
1. Tietz Textbook of Clinical Chemistry, Second edition. Edited by CA Burtis, ER Ashwood. Philadelphia, WB Saunders Company, 1994
2. Scharschmidt BF, Blanckaert N, Farina FA, et al: Measurement of serum bilirubin and its mono- and diconjugates: Applications to patients with hepatobiliary disease. Gut 1982;23:643-649
3. American Academy of Pediatrics Provisional Committee on Quality Improvement and Subcommittee on Hyperbilirubinemia. Practice Parameter: Management of hyperbilirubinemia in the healthy term newborn. Pediatrics 1994;94:558-565