The short answer
Bile acids are made from cholesterol in the liver, stored and concentrated in the gallbladder, released after a meal under the influence of CCK, used to emulsify fat and form micelles, then recaptured in the terminal ileum and returned to the liver in portal blood. The pool is only 2–4 g but cycles 6–10 times a day, because more than 95% is conserved on each pass. The 0.2–0.6 g lost daily in the faeces is exactly what new synthesis replaces.
The ten steps
- Synthesis. Cholesterol is converted by CYP7A1, the rate-limiting enzyme, into the primary bile acids cholic acid and chenodeoxycholic acid. They are conjugated with glycine or taurine, which keeps them ionised and trapped in the gut lumen until the ileum. BSEP pumps them into the bile canaliculus. Making bile acids is the body's main route for eliminating cholesterol.
- Storage. Between meals the sphincter of Oddi is closed, so bile backs up into the gallbladder. The epithelium absorbs sodium, chloride and water, concentrating bile salts from about 25 to about 150 mmol/L.
- Release. Fat and amino acids in the duodenum make I cells release cholecystokinin, which contracts the gallbladder and relaxes the sphincter of Oddi. This is why biliary colic classically starts 30 to 60 minutes after a fatty meal.
- Fat digestion. Two separate stages — emulsification and micelle formation, which are not the same thing.
- Ileal reabsorption. ASBT takes conjugated bile acids up actively in the terminal ileum, IBABP carries them across the cell, and OSTα/β exports them to portal blood.
- Return to the liver. They travel bound to albumin and are extracted by NTCP and OATPs so efficiently — around 80–90% in one pass — that serum levels stay low.
- Colonic bacteria. The few per cent that escape are deconjugated and 7α-dehydroxylated: cholic acid becomes deoxycholic acid, chenodeoxycholic acid becomes lithocholic acid. Some bacteria also make ursodeoxycholic acid.
- Feedback. Bile acid in the ileal enterocyte activates FXR, which makes FGF19; this travels in portal blood and switches off CYP7A1. A second, local FXR–SHP brake acts in the hepatocyte.
- Signalling. Bile acids are hormones as well as detergents, acting on FXR and on the membrane receptor TGR5, which releases GLP-1 from intestinal L cells.
- The whole circuit, and what happens when each step breaks.
When the circuit breaks
| Condition | What breaks | Result |
|---|---|---|
| Limited ileal resection (often <~100 cm) | Uptake falls; synthesis compensates | Bile acid diarrhoea — responds to a sequestrant |
| Extensive ileal resection (often >~100 cm) | Losses exceed maximal synthesis; the pool shrinks | Steatorrhoea, fat-soluble vitamin and B12 deficiency, gallstones, oxalate kidney stones |
| Cholecystectomy | The reservoir is lost; bile flows continuously | Usually nothing; loose stools in a minority |
| Cholestasis | Secretion into bile, or drainage, fails | Jaundice, itch, pale stools, steatorrhoea, a raised INR |
| Antibiotics | Fewer bacteria making secondary bile acids | Higher risk of Clostridioides difficile infection |
Why surgeons care
Gastric bypass changes where and when bile meets food: the biliopancreatic limb carries bile past the duodenum to meet nutrients in the jejunum. Serum bile acids and FGF19 rise after sleeve gastrectomy and bypass, and that signalling is part of the improvement in glucose control that appears before much weight is lost. Metabolic surgery is, in part, bile acid surgery.
Practise on a patient
The gallbladder patient in the simulator is clerked from the referral stem, with you choosing the questions.
Related pages
Commonly confusedEmulsification vs micelles1 µm versus 5 nm — two stages, two jobs.ClinicalBile acid diarrhoeaAfter ileal resection, and when a sequestrant makes it worse.ClinicalWhy the INR rises in obstructionThe clotting consequence of no bile in the gut.OverviewThe patient with jaundicePart 2 of the book.
Other topics
Everything on the site sits under one of these.
Jaundice & liver testsWhy a patient turns yellow, how to tell the three types apart at the bedside, and how to read the liver function tests that follow.The acute abdomenThe commonest reason a student is sent to clerk a patient. Where the pain started, where it went, and what that movement tells you.Gastrointestinal bleedingBlood from the top and blood from the bottom: what to ask, which drug history matters, and what must not be called haemorrhoids.Hernia & the groinA lump in the groin, and the three questions that decide whether it can wait until the morning or needs a surgeon tonight.Calcium & the parathyroidFour glands defending one number, the hypercalcaemic patient, the parathyroid operation, and the tingling fingers the morning after a thyroidectomy.Endocrine & bariatric surgeryThe thyroid, the parathyroids and the metabolic patient — the operations this unit does most, and the histories behind them.Wounds & the lower limbVenous, arterial or neuropathic. Three ulcers that look similar on a ward round and are told apart almost entirely by the history.