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Jaundice, or icterus, develops when plasma bilirubin levels are approximately 2.5 to 3 milligrams per deciliter, leading to yellow discoloration of the skin, sclerae, and mucous membranes.

Bilirubin is produced and eliminated through a normal physiological process that begins with the breakdown of red blood cells.

Macrophages degrade hemoglobin into globin and heme.

Globin is converted into amino acids for reuse, while heme is turned into biliverdin by heme oxygenase. Biliverdin reductase then reduces biliverdin to lipid-soluble unconjugated bilirubin.

Unconjugated bilirubin binds to albumin for transport in the bloodstream to the liver.

In hepatocytes, the enzyme uridine diphosphate-glucuronosyl transferase conjugates bilirubin with glucuronic acid, forming water-soluble conjugated bilirubin.

The liver then secretes this conjugated bilirubin into bile, which is excreted into the intestine.

Disruption at any stage of bilirubin metabolism, whether due to increased production, impaired hepatic uptake or conjugation, or obstruction of bile excretion, can lead to elevated serum bilirubin levels.