Question 5

College Answer

Bile is produced by hepatocytes, excretion via cannaliculus and biliary tree. It is stored and concentrated in the gallbladder. Bile contains water, bile acids and bile salts, bile pigments and electrolytes. Some detail was expected regarding each of these and comment on “Primary bile acids”, conjugation with taurine and glycine and production of “bile salts”. It was often not appreciated bacteria in gut produce “secondary” bile acids such as deoxycholate and lithocholic acid. Additional credit was given for discussing “Unconjugated bilirubin” being derived from “heme” component of haemoglobin (85%) is carried via albumin to liver for conjugation via UDP-gluconuryl transferase to “conjugated bilirubin” and that gut bacteria generate water soluble urobilinogen, enterohepatic recycling and excretion in urine.The major role of bile is in lipid, cholesterol and lipid soluble vitamin absorption with a minor role in excretion of bile pigments. It was expected candidates would describe the  emulsification of fat via bile salts and lipid micelle formation to facilitate absorption.

Discussion

Composition of bile: 

• 95% water and 5% organic and inorganic solutes
• Ionic composition same as plasma; more alkaline; concentrated and acidic in the gallbladder
• Organic molecules:
  • Bile salts (3-45 mmol/L), total pool ~ 3g
  • Bilirubin (1-2 mmol/L)
  • Cholesterol (2.5-8.0 mmol/L)
  • Lipids (20g/L)
  • <1g/L protein (albumin, IgA, transferring, apolioproteins)
• Bile salts are salts of bile acids which are products of cholesterol metabolism
  • Primary (cholic and chenodeoxycholic acids) are synthesised by hepatocytes
  • Secondary (deoxycholic and lithocholic acids) are products of gut bacteria

Formation of bile:

• 95% of secreted bile salts are reabsorbed in the terminal ileum
• Recirculate to the hepatocytes via the portal vein, and are actively transported into bile
• Bile salt-dependent bile secretion is due to the osmotic effects of bile salts on water
• Bile salt-independent bile secretion is due to the osmotic effects of other organic molecules such as glutathione, bilirubin, bicarbonate and organic conjugates
• In the bile ducts, more fluid (~40%) is added and the bile is alkalinised
• In the gall bladder, bile is concentrated, and a lot of the ions and water are reclaimed

Function of bile:

• Digestive functions: emulsification of dietary fat and increased access for lipases, which improves lipid breakdon and the absorption of fat-soluble micronutrients
• Excretory functions: main mechanism of excreting cholesterol and bilirubin, as well as lipid-soluble xenobiotics
• Immune functions: bile contains IgA and IgG
• Growth stimulus: contains various growth promoters and signalling molecules which act as trophic stimuli for enterocytes

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Boyer, James Lorenzen, and Carol Jean Soroka. "Bile formation and secretion: An update." Journal of Hepatology 75.1 (2021): 190-201.

Esteller, Alejandro. "Physiology of bile secretion." World journal of gastroenterology: WJG 14.37 (2008): 5641.

Chiang, J. Y. "Regulation of bile acid synthesis." Front biosci 3.4 (1998): d176-93.

Carey, Martin C., and Donald M. Small. "Micelle formation by bile salts: physical-chemical and thermodynamic considerations." Archives of internal medicine 130.4 (1972): 506-527.

Hofmann, Alan F. "The continuing importance of bile acids in liver and intestinal disease." Archives of internal medicine 159.22 (1999): 2647-2658.