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Bilirubin Metabolism

Bilirubin Metabolism: Physiology Pre-Hepatic Macrophages in bloodstream & spleen phagocytize aging & damaged red blood cells (RBCs) Hemoglobin (Hb) is separated from RBC during phagocytosis & released into cytoplasm of macrophage Hb is broken down into heme & globin Circulating macrophages break down heme-containing proteins present in bloodstream (eg. myoglobin, cytochrome enzymes) Heme-oxygenase enzyme cleaves heme into biliverdin, Fe²⁺ & carbon monoxide Biliverdin reductase converts biliverdin to hydrophobic unconjugated bilirubin (UCB) Hepatic Albumin binds UCB in bloodstream & transports it to liver sinusoids (leaky capillaries allow for exchange of substances between blood & liver) UGT1A1 enzyme facilitates conjugation of UCB with glucuronic acid Conjugated bilirubin (CB) is water soluble & becomes component of bile A portion of urobilinogen returns to liver & becomes component of bile Bile is stored in gallbladder or secreted into small intestine through common bile duct Post-Hepatic Gut bacteria proteases process CB into urobilinogen ~20% of urobilinogen is absorbed & transported back to liver via portal system ~80% of urobilinogen is processed into urobilin & stercobilin by gut bacteria A portion of re-absorbed urobilinogen bypasses liver & enters systemic circulation Urobilin & stercobilin is excreted in feces Authors: Ethan Pichlyk* Taylor Krawec Reviewers: Annie Pham Emily J. Doucette Sarah Smith* *MD at time of publication Legend: Pathophysiology Urobilinogen is oxidized into urobilin in the kidneys Urobilin is excreted in urine Yellow urine Brown stool Mechanism Sign/Symptom/Lab Finding Complications Published July 24, 2025 on www.thecalgaryguide.com