Enterohepatic circulation and bile acid reabsorption (terminal ileum)
Core concept
- Bile acid pool ~3-4 g, recycled 4-12 times per day -> ~20-30 g delivered to the gut daily
- ~95% reabsorbed; ~5% (0.2-0.6 g/day) lost in stool and replaced by hepatic synthesis
- Synthesis is the only route of cholesterol elimination from the body
- The circuit
- Liver: cholesterol -> CYP7A1 (rate-limiting) -> primary bile acids cholic and chenodeoxycholic acid, conjugated with glycine/taurine
- Secreted into canaliculus via BSEP; stored in gallbladder; released on CCK
- Terminal ileum: ASBT (apical sodium-dependent bile acid transporter, SLC10A2) - active, Na-coupled reabsorption
- Portal vein -> hepatocyte uptake via NTCP and OATPs -> resecreted
- FXR is the thermostat
- Ileal bile acids -> FXR -> FGF19 -> portal vein -> hepatic FGFR4 -> suppresses CYP7A1
- Hepatic FXR -> SHP -> also suppresses CYP7A1
- -> loss of ileal bile acid uptake removes the brake -> upregulated synthesis
- Colonic bacteria deconjugate and 7-alpha-dehydroxylate -> secondary bile acids deoxycholic and lithocholic acid
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