Hepatobiliary Physiology — Bile

Bile

• dark green solution produced by the liver to facilitate absorption of fat and fat-soluble vitamins (ADEK) through emulsification.
• Liver produces 1 L bile/day → passes into gallbladder for concentration to 20% volume
• Produced by hepatocytes
• Excreted via canaliculus and biliary tree
• Stored and concentrated in the gallbladder
• Bile contains
  1. Bile salts (sodium and potassium salts of bile acids)
  2. Bilirubin
  3. Water and electrolytes: Na, Cl, K, Ca, bicarb
  4. Lipids: Cholesterol, Fatty acids, lecithin
  5. Proteins

Bile Acids:

• Are produced from cholesterol (from diet or from fat metabolism)
• Cholesterol is first converted to cholic acid or chenodeoycholic acid
• These acids combine with glycine and taurine to form glycol- and tauro- conjugated bile acids.
• The salts of these acids (mainly sodium, and potassium) are then secreted into bile.

Bile salts:

• Are amphipathic, and act as emulsifiers of lipid
  • Break up large fat globules into smaller micelles, which can then be absorbed.
• Form micelles
  • help in the absorption of (1) fatty acids, (2) monoglycerides, (3) cholesterol, and (4) other lipids from the intestinal tract.
• Are absorbed in the terminal ileum, and recycled by the portal circulation (Enterohepatic circulation) along with secondary bile salts produced by gut bacteria such as deoxycholate and lithocholic acid

Bilirubin:

• Catabolic product of heme metabolism
  • hemoglobin, myoglobin, cytochromes, catalase, peroxidase, and tryptophan pyrrolase
  • 80% from Hb (250 to 400 mg daily)
  • 20% other heme proteins and a rapidly turning-over small pool of free heme
• Pathway:
  • Haeme + Haem oxygenase → biliverdin
  • Biliverdin + biliverdin reductase → bilirubin
  • Free bilirubin + albumin → transported to hepatocytes
  • Conjugated with glucuronide to ↑ water solubility
  • Excreted to bile canniliculus
  • Secreted to gut at D2 (duodenum)
  • Intestinal flora hydrolyse and reduce → urobilinogen
  • 3 fates:
    • Gut bacteria form the dark pigment stercobilin, which is egested in the faeces
    • Urobilinogen reabsorbed unchanged by the portal system and recycled by the liver
    • Remainder is reabsorbed by the portal system and then excreted in the urine

Formation and Handling

Formation and handling of bile salts:

1. 1° bile acids (cholic acid and chenodeoxycholic acid) are produced in hepatocytes from cholesterol → then conjugated with glycine (75%) and taurine (25%) to ↑ their H2O solubility → then actively excreted in bile
2. They are metabolised by intestinal bacteria (esp large intestines) to form 2° bile acids (deoxycholic acid and lithocholic acid)
3. 1° and 2° bile acids become “Bile salts” when they combine with Na+ or K+
4. 95% of bile salts are reabsorbed in terminal ileum → recirculated to liver via the portal circulation (“enterohepatic circulation”) → so both 1° and 2° bile salts can be found in bile!
5. Only 5% of bile salts are lost in faeces

Turnover of bile salts:

• Rate of hepatic production of bile acid (~0.2-0.5 g/day) EQUALS rate of bile acid loss in the intestines → this low rate of production/loss is due to bile acid recycling via “enterohepatic circulation”
• The body has a “total” storage pool of bile acids of 3 g → during a meal, 9 g of bile salts are needed (Ie. this pool is recycled 3X). Thus, with 3x meals/day the “effective” bile acid pool can ↑ up to 27 g (Ie. this 3g pool is recycled up to 9X)

Release: (relaxation of sphincter of Oddi) takes place via

• negative feed back from bile salt reabsorption in terminal ileum
• acid chyme in duodenum releasing secretin -> increases HCO3- rich secretions from duct cells
• CCK
• gastrin
• nervous control

Functions

1. Facilitate intestinal digestion of lipids → aids pancreatic lipase activity
2. Enhances intestinal absorption of lipids (fat, cholesterol, phospholipids, and fat-soluble vitamins)
   • by emulsifying lipids (by ↓ surface tension → breaks down fat), and
   • forming “micelles” (as it is amphipathic)
3. Keeps cholesterol solubilised within gallbladder (Ie. prevents gallstones!)
4. Induces intestinal motility (Ie. endogenous laxative)
5. Choleretic action → bile salts stimulate the hepatocytes to produce MORE bile (via Bile-dependent biliary secretion)

Bianca / JC 2020

Answer by Bianca, JC