Liver Physiology 6: Biliary Secretion And Enterohepatic Secretion Salts

Question 1

What is bile?

Answer 1

Complex lipid-rich micellar solution (water, inorganic electrolytes and organic solutes- bile acids, phospholipids, cholesterol, bile pigments)

Isosmatic with plasma

500-600mls per day

Formation depends on the hepatic synthesis and canalicular secretion of bile acids (=major organic anion in bile)

Maintenance of hepatic bile formation is essential for normal liver function

Most bile acids (95%) secreted by hepatocyte have been previously secreted into intestine (enterohepatic circulation)

Question 2

Bile acids

Answer 2

Synthesised from cholesterol in pericentral hepatocytes of the acini

Cholesterol (lipophilic)- colic acid and chenodeoxycholic acid (water soluble) (primary bile acids)

CA and CDCA are conjugated (N-acyl amidated with glycine or taurine) before secretion into the bile canaliculus

Conjugation enhances the hydrophilicity and acidic strength of the side chain (pKa = 5.0 unconjugated; pKa = 3.9 glycine conjugate; pKa 2.0 taurine conjugate

Conjugation decreases passive diffusion of bile acids across cell membranes during transit through EHC (ie keeps intraluminal)

Question 3

Amphipathic (hydrophilic and hydrophobic parts)

Answer 3

reduce surface tension and aid emulsification

Question 4

Emulsification

Answer 4

Fat (TG) is insoluble in water

Emulsification increases surface area for lipolysis. Stable emulsion important for the close apposition of lipase and TG

Lipases act at surface of emulsified droplets and liberate FA from the glycerol backbone of TG (lipolysis)

Question 5

Functions of bile acids

Answer 5

Induce bile flow (osmotic effect) & secretion of biliary lipids (PL and cholesterol)

Digestion of dietary fats – by solubilising lipids and lipid digestion products as mixed micelles facilitating aqueous diffusion across intestinal mucosa

Facilitates protein absorption – accelerating hydrolysis by pancreatic proteases

Cholesterol homeostasis – facilitates dietary absorption / elimination as BA are water-soluble end-products of cholesterol catabolism. Induce bile flow and solubilise cholesterol – enabling movement from hepatocyte to intestinal lumen

Antimicrobial (physicochemical + inducing anti-microbial genes)

Prevents calcium gallstones and oxalate renal stones

Question 6

Enterohepatic circulation (1)

Answer 6

FASTED – bile acids travel down biliary tract to GB (concn x10)

FED – CCK (cholecystokinin) released from duodenal mucosa

CCK – relaxes SO and contracts GB releasing concentrated solution of mixed micelles (BA, PL, cholesterol)

Question 7

Enterohepatic circulation (2)

Answer 7

Bile acids (conjugated) remain intraluminal

Actively transported (reabsorbed) via the apical sodium bile acid transporter (ASBT)

Re-enters liver via portal circulation

Bile acids taken up by hepatocyte and (re-conjugated) secreted into biliary canaliculi

Question 8

Enterohepatic circulation (3)

Answer 8

Usually 2-3 cycles per meal

Bile acid feedback mechanism – inhibition of CYP7A1 (cytochrome P450 7A1) = cholesterol 7𝛼 hydroxylase

Question 9

Enterohepatic circulation (4)

Answer 9

Rare inherited defects in bile acid synthesis

Deconjugation of bile acids (small bowel bacterial overgrowth)

Cholecystectomy (5% diarrhoea) – daily bile acid secretion is not altered much. Bile is ‘stored’ in proximal small intestine – likely big ‘shift’ to distal small intestine ‘overwhelms’ transport mechanism or feedback mechanism

Ileal resection or disease – unabsorbed bile acids enter colon where inhibit water absorption / induce secretion resulting in ‘bile salt diarrhoea’

Question 10

Enterohepatic circulation (5)

Answer 10

Biliary obstruction – CBD stone, pancreatic carcinoma – intestinal malabsorption of fat soluble vitamins and fat resulting in steatorrhoea and develop jaundice