Describe the composition and functions of bile. Explain the enterohepatic circulation of bile salts and the functions of the gall bladder.

Normal Values

Composition

Formation of Bile Salts

Cholesterol → 7α-hydroxylase (rate-limiting) → Primary bile acids — cholic and chenodeoxycholic acid → Conjugated with glycine or taurine → Bile salts → Bacterial action in the gut → Secondary — deoxycholic, lithocholic acid

• Conjugation makes them water soluble and effective at duodenal pH
• Bile acid synthesis is the chief route of cholesterol excretion

Functions of Bile Salts

• Emulsification — they are amphipathic; they lower surface tension and break large fat globules into fine droplets, greatly increasing the surface area for lipase
• Micelle formation — the critical function. Micelles carry the products of fat digestion to the brush border for absorption
• Absorption of fat-soluble vitamins A, D, E and K
• Choleretic action — bile salts themselves stimulate further bile secretion
• Keep cholesterol in solution → prevent gallstone formation
• Mild laxative and antiseptic action

Enterohepatic Circulation

Bile salts secreted into duodenum → Act in jejunum on fat → Actively reabsorbed in the terminal ileum → Portal vein → liver → Re-secreted into bile

• 95% is reabsorbed; only 5% is lost in faeces and replaced by fresh synthesis
• The pool of 3.5 g circulates 6–8 times a day
• This economy allows a small pool to do the work of a much larger one

Micelle Formation

• Forms only above the critical micellar concentration of bile salts
• Carries monoglycerides, fatty acids, cholesterol and fat-soluble vitamins
• Ferries them across the unstirred water layer to the brush border — which lipid droplets cannot cross
• Increases fat absorption about 3-fold; without bile salts, 25–40% of ingested fat is lost in stool
• The bile salts themselves are not absorbed here — they are released and travel on to the ileum

Bile Pigment Excretion

• About 300 mg of bilirubin is excreted daily
• Conjugated bilirubin → gut → bacterial action → urobilinogen → stercobilinogen (brown colour of stool)
• Bile is the only route for excreting bilirubin, cholesterol and heavy metals such as copper

Gall Bladder

• Capacity 30–60 mL, yet it stores the bile produced over 12 hours
• Achieves this by concentrating bile 5–20 times through active Na+ absorption with water following
• CCK contracts the gall bladder and relaxes the sphincter of Oddi
• Also contracted by vagal stimulation
• Gall bladder bile is more acidic (pH 7.0) than hepatic bile

Regulation of Bile Secretion

Applied Aspects

• Gallstones — form when bile is supersaturated with cholesterol relative to bile salts and lecithin. Risk factors — the classical "5 F": female, fat, fertile, forty, fair
• Obstructive jaundice → no bile in gut → clay-coloured stool, steatorrhoea, deficiency of vitamin K → bleeding tendency with a prolonged prothrombin time
• Ileal resection or Crohn disease → enterohepatic circulation broken → bile salt deficiency → steatorrhoea, and B12 deficiency
• Cholecystectomy is well tolerated — the bile duct dilates and bile flows continuously into the gut
• Cholestyramine binds bile salts in the gut — used for the pruritus of cholestasis and to lower cholesterol
• Ursodeoxycholic acid can dissolve small radiolucent cholesterol stones
• Charcot triad — fever, jaundice and right upper quadrant pain indicates ascending cholangitis