Bilirubin is formed in the reticuloendothelial system during the degradation of aged erythrocytes. The heme portion from hemoglobin and from other heme-containing proteins is removed, metabolized to bilirubin, and transported as a complex with serum albumin to the liver. In the liver, bilirubin is conjugated with glucuronic acid for solubilization and subsequent transport through the bile duct and elimination via the digestive tract.
80 – 85% of bilirubin produced daily originates from haemoglobin released by the breakdown of senescent erythrocytes, the remaining 15 – 20% results from the breakdown of haem-containing proteins such as myoglobin, cytochromes, catalases and from bone marrow as a result of ineffective erythropoiesis. A number of diseases affect one or more of the steps involved in the production, uptake, storage, metabolism and excretion of bilirubin. Depending on the disorder unconjugated or conjugated bilirubin or both are major contributors to the resulting hyperbilirubinemia.
Diseases or conditions which, through hemolytic processes, produce bilirubin faster than the liver can metabolize it, cause the levels of unconjugated (indirect) bilirubin to increase in the circulation. Liver immaturity and several other diseases in which the bilirubin conjugation mechanism is impaired cause similar elevations of circulating unconjugated bilirubin. Bile duct obstruction or damage to hepatocellular structure causes increases in the levels of both conjugated (direct) and unconjugated (indirect) bilirubin in the circulation.
Hyperbilirubinemia can be classified as follows:
Prehepatic Jaundice: Diseases of prehepatic origin with predominantly unconjugated hyperbilirubinemia include corpuscular haemolytic anemias e.g. thalassemia and sickle cell anemia; extracorpuscular haemolytic anemia e.g. blood transfusion reaction due to ABO and Rh incompatibility; neonatal jaundice and haemolytic disease of the newborn.
Hepatic Jaundice: Diseases of hepatic origin with predominantly conjugated hyperbilirubinemia include acute and chronic viral hepatitis, liver cirrhosis and hepatocellular carcinoma.
Post hepatic Jaundice: Diseases of post-hepatic origin with predominantly conjugated hyperbilirubinemia include extrahepatic cholestasis and liver transplant rejection.
Chronic congenital hyperbilirubinemias include the unconjugated hyperbilirubinemias Crigler-Najjar syndrome and Gilbert's syndrome as well as the conjugated hyperbilirubinemias Dubin-Johnson syndrome and Rotor syndrome. The differentiation between chronic congenital hyperbilirubinemias and acquired types of bilirubinemia is accomplished via the measurement of bilirubin fractions and the detection of normal liver enzyme activities.
Test principle: Colorimetric diazo method
| Adults | up to 21 μmol/L | up to 1.2 mg/dL |
| Children with age ≥ 1 month | up to 17 μmol/L | up to 1.0 mg/dL |
High risk for developing clinically significant hyperbilirubinemia: Newborns: Term and near-term
| Age of newborn | 95th percentile | 95th percentile |
| 24 hours | ≥ 137 μmol/L | ≥ 8.0 mg/dL |
| 48 hours | ≥ 222 μmol/L | ≥ 13.0 mg/dL |
| 84 hours | ≥ 290 μmol/L | ≥ 17.0 mg/dL |
Levels > 95 th percentile: such levels of hyperbilirubinemia have been deemed significant and are generally considered to require close supervision, possible further evaluation, and sometimes intervention.
Refer to www.bilitool.org for information on age-specific (postnatal hour of life) serum bilirubin values.