enterohepatic circulation

Enterohepatic circulation describes the recycling pathway in which compounds synthesized or metabolized by the liver are secreted into bile, delivered to the small intestine, reabsorbed (often in the terminal ileum), and returned to the liver via the portal vein for re-secretion. Bile acids are the prototypical substrate: primary bile acids (cholic acid, chenodeoxycholic acid) are synthesized from cholesterol in hepatocytes, conjugated with glycine/taurine, secreted into bile, and stored in the gallbladder. After a meal, cholecystokinin triggers gallbladder contraction, releasing bile acids into the duodenum to emulsify fats and aid absorption of fat-soluble vitamins (A, D, E, K). Bacteria in the colon can deconjugate and dehydroxylate some bile acids into secondary bile acids (deoxycholic acid, lithocholic acid). Roughly 95% of bile acids are actively reabsorbed via the apical sodium-dependent bile acid transporter (ASBT) in the terminal ileum, entering portal circulation bound to albumin, and are taken up by hepatocytes via NTCP/OATP transporters for re-secretion—completing the cycle. Only ~5% is lost in feces daily, replaced by de novo hepatic synthesis. Clinical relevance: Terminal ileum resection or disease (e.g., Crohn's) disrupts bile acid reabsorption, causing bile acid malabsorption, diarrhea (bile acid diarrhea), and steatorrhea with fat-soluble vitamin deficiencies. Cholestyramine and other bile acid sequestrants work by binding bile acids in the gut lumen, interrupting enterohepatic circulation, lowering LDL cholesterol (since the liver upregulates LDL receptors to synthesize more bile acids) and are used to treat bile acid diarrhea and pruritus of cholestasis. Many drugs (e.g., NSAIDs, oral contraceptives, digoxin, and glucuronidated compounds) undergo enterohepatic recirculation, prolonging their half-life; disruption by antibiotics (killing gut flora needed for deconjugation) can reduce drug efficacy (e.g., reduced OCP efficacy, though this is somewhat controversial) or drug reabsorption. Unconjugated bilirubin also undergoes some enterohepatic circulation, particularly in neonates with immature gut flora, contributing to neonatal jaundice.