bilirubin

Bilirubin is a yellow-orange bile pigment produced during the breakdown of heme, primarily from aging or damaged red blood cells processed by macrophages in the reticuloendothelial system. It exists in two major forms: unconjugated (indirect) bilirubin, which is fat-soluble, and conjugated (direct) bilirubin, which becomes water-soluble after hepatic processing.

Unconjugated bilirubin is transported in the blood bound to albumin to the liver, where hepatocytes conjugate it with glucuronic acid via the enzyme UDP-glucuronosyltransferase, forming bilirubin diglucuronide (conjugated bilirubin). This conjugated bilirubin is excreted into bile and reaches the intestine. In the gut, bacterial enzymes can deconjugate and reduce bilirubin to urobilinogen; most urobilinogen is converted to stercobilin and excreted in feces, while some is reabsorbed and may be excreted in the urine as urobilin.

Clinical relevance: total bilirubin is the sum of direct and indirect bilirubin. Normal total bilirubin is typically around 0.3–1.2 mg/dL, though reference ranges vary. Elevations cause jaundice. Patterns of elevation help localize the process: prehepatic (increased unconjugated bilirubin due to hemolysis), hepatic (impaired conjugation or hepatocellular disease), and posthepatic (obstructive cholestasis with increased direct bilirubin).

In newborns, physiological jaundice results from immature hepatic conjugation; severe unconjugated hyperbilirubinemia risks kernicterus and may require phototherapy or exchange transfusion. Bilirubin measurement is a standard part of liver function assessment and newborn screening.