The final product of heme degradation and is insoluble in plasma.

Conjugated in the liver and excreted in bile.

Newborn production per day is 6 to 8 mg per kg per day, twice the production in adults.

Adult production levels occur within 10-14 days after birth.

Elevated levels can be the result of increased production, or impaired hepatic uptake, conjugation or excretion.

Measurement of total bilirubin includes both unconjugated (indirect) and conjugated (direct) bilirubin.

Unconjugated bilirubin is a breakdown product of heme.

The liver is responsible for clearing the blood of unconjugated bilirubin, by conjugating it, to make it water-soluble through an enzyme named UDP-glucuronyl-transferase.

The bilirubin uridine diphosphate glucuronosyl transferase (bilirubin-UGT) enzyme converts the toxic form of bilirubin, which is unconjugated bilirubin to its nontoxic form, conjugated bilirubin, making it able to be dissolved and removed from the body.



The bilirubin-UGT enzyme is primarily found in cells of the liver, where bilirubin glucuronidation takes place. 



Conjugated bilirubin is dissolved in bile and excreted with solid waste.

Conjugated hyperbilirubinemia associated with extrahepatic cholestasis, Dubin-Johnson syndrome, Rotors syndrome, pregnancy, hepatocellular disease, end-stage liver disease, infiltrative liver disease, sepsis, drugs, total parenteral nutrition, post organ transplant and sickle cell crisis.

Unconjugated hyperbilirubinemia associated with extravascular hemolysis, intravascular hemolysis, dyserythropoiesis, extravasation, portosystemic shunts, drugs, Gilbert disease, Crigler-Najar syndrome, hyperthyroidism, cirrhosis, Wilson disease, chronic hepatitis, neonatal and congestive heart failure.

Unconjugated bilirubin of greater than 4 mg/dL in a hemolytic process suggests accompanying liver dysfunction.

Levels are altered by heritable and a genetic variations of uridine diphosphate-glucuronyltransferase 1, and by enzymes involved with bilirubin production from heme including heme oxygenase.

Bilirubin has protective properties including antioxidant, anti-inflammatory, and anti-proliferative effects.

Relatively higher levels of bilirubin is associated with lower risk of respiratory disease and all cause mortality (Horsfall LJ et al).

Among patients with normal range bilirubin levels, relatively higher levels was associated inversely with the incidence of lung cancer, COPD and all cause mortality (Horsfall LJ et al).

Increased reduction associated with increased risk of gallstone disease.

Gilbert syndrome has been found to strongly protect against cardiovascular disease in the Framingham Offspring Study, indicating a protective effect of moderately increased bilirubin.

Bilirubin and calcium can combine to form calcium-bilirubin salts which may grow and become pigmented gallstones.

A core calcium-bilirubin is often found in cholesterol gallstones, the most common gallstone in the Western world.

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