Bilirubin Direct, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Approximately 85% of the total bilirubin produced is derived from the heme moiety of hemoglobin while the remaining 15% is produced from the 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 mono- and diglucuronide, which are excreted in the bile. Direct bilirubin is a measurement of conjugated bilirubin.
Jaundice can occur as a result of problems at each step in the metabolic pathway. Disorders may be classified as those due to: increased bilirubin production (eg, hemolysis and ineffective erythropoiesis), decreased bilirubin excretion (eg, obstruction and hepatitis), and abnormal bilirubin metabolism (eg, hereditary and neonatal jaundice).
Inherited disorders in which direct bilirubinemia occurs include Dubin-Johnson syndrome and Rotor syndrome. Jaundice of the newborn where direct bilirubin is elevated includes idiopathic neonatal hepatitis and biliary atresia. The most commonly occurring form of jaundice of the newborn, physiological jaundice, results in unconjugated (indirect) hyperbilirubinemia. Elevated unconjugated bilirubin in the neonatal period may result in brain damage (kernicterus). Treatment options are phototherapy and, if severe, exchange transfusion.
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. In hepatobiliary diseases of various causes, bilirubin uptake, storage, and excretion are impaired to varying degrees. Thus, both conjugated and unconjugated bilirubin is retained and a wide range of abnormal serum concentrations of each form of bilirubin may be observed. Both conjugated and unconjugated bilirubin are increased in hepatocellular diseases such as 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.
Evaluation of jaundice and liver functions
Direct bilirubin levels must be assessed in conjunction with total and indirect levels and the clinical setting.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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 low results may be seen.
It is important to remember that in addition to the mono- and diglucuronide fraction, the direct bilirubin assay will also measure the delta bilirubin fraction. Delta bilirubin is a conjugated bilirubin that is covalently bound to albumin. Therefore, the clearance of delta bilirubin from the serum is similar to the clearance of albumin which has a half-life of approximately 21 days.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
> or =12 months: 0.0-0.3 mg/dL
Reference values have not been established for patients who are <12 months of age.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Tietz Textbook of Clinical Chemistry. Edited by CA Burtis, ER Ashwood. Philadelphia, PA, WB Saunders Company, 1994
2. Roche/Hitachi Modular Analytics Reference Guide, Vol 7