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