NME2.10: bile and the gall bladder29/01/08

Learning Outcomes

Describe the composition and functions of bile

  • Bile is a golden-yellow, viscous and highly complex secretion that oxidises to a green colour on exposure to air
  • The two primary functions of bile are:
  • To provide the sole excretory route for many solutes not filtered through the kidneys
  • Bile salts and acids are required for normal lipid digestion
  • Hepatocytes actively secrete bile into the canaliculi as aisotonic fluid which is initially slightly alkaline:
  • High sodium/chloride content
  • Biliary lipids including bile acids (predominantly), phospholipids and cholesterol
  • 1-2g bilirubin per litre
  • Primary bile acids are synthesised by hepatocytes – cholic acid and chenodeoxycholic acid–from cholesterol, and appear in both acid and salt forms (mostly cholic/cholate)
  • Secondary bile acids are modified in the intestine:
  • Deoxycholic acid is the result of glycine conjugation
  • Lithocholic acidis the result of taurine conjugation (vegetarians have limited taurine intake)
  • These secondary bile acids are thenreabsorbed via the enterohepatic circulation(lithocholate mostly lost)
  • The hepatic ducts secrete a watery bicarbonate-rich fluid into the bile producing up to 1 litre per day of so-called hepatic bile–choleresis

Describe the mechanisms of secretion of bile

  • Bile acids are taken up into hepatocytes in various ways:
  • Both glycine/taurine conjugated and unconjugated bile saltsare imported using a sodium co-transporter
  • Neutral, protonated bile acids diffuse across the basolateral membrane
  • Bile acids may be transported within the cells using binding proteins before conjugation:
  • Sulfate/glucuronate conjugated bile acids exit via the MRP2 transporter
  • Glycine/taurine conjugated bile acids (more common) exit via the BSEP[TG1]transporter

Describe the control of biliary secretion

  • Total bile flow is the sum of the canalicular flow and the ductular flow
  • Canalicular flow increases linearly with bile acid secretion and so is said to have abile acid dependent component which makes up the bulk of the canalicular flow
  • Ductular flow is roughly constant and regulated by stimulatory agents including secretin, glucagon and VIP

Explain the role of the gall bladder and its control

  • The gall bladderis not essential to bile secretion but serves as a store during inter-digestive periods in which it concentrates bile acids up to 20-fold
  • Bile is rerouted into the gall bladder by tonic contraction of the sphincter of Oddi, forcing bile from the common bile duct up the cystic duct
  • The gall bladder iso-osmotically removes salts and water from bile, concentrating the remaining solutes:
  • Sodium ions are exchanged for hydrogen ions – net secretion of H+
  • Chloride ions are exchanged for bicarbonate ions
  • During fasting, up to 50% of hepatic bile is stored in the gall bladder
  • CCK and ACh stimulate gall bladder contraction / emptying in digestion

Outline how the composition of bile may contribute towards gallstone formation

  • Most gallstones are primarily made up of cholesterol (80%)
  • Formation of gallstones (cholelithiasis) may result from reduced cholesterol elimination and/or impaired bile secretion
  • Cholesterol secreted normally in bile exists as mixed micelles which allow it to remain in solution; insufficient bile acid concentration may cause excess cholesterol to be left behind as aqueous vesicles
  • Unstable cholesterol-rich vesicles tend to aggregate and form the basis from which crystals may nucleate, forming gallstones

[TG1]Member of the ABC superfamily