Physiology of bile

Describe the composition, formation and functions of bile

Composition

Approximately 1 L of bile is produced by hepatocytes each day. It is stored in the gallbladder and concentrated to ~200 mL via water and electrolyte reabsorption.

Bile composition - BILE-WASP
  • Bicarbonate
  • Immunoglobulins: IgG and IgA
  • Lipids
  • Electrolytes: Concentrations similar to plasma
  • Water (osmolality ~285 mOsm/kg)
  • Acids / Salts (bile acids / bile salts)
    • Primary bile acids are synthesised in hepatocytes
    • Primary bile acids are conjugated with glycine or taurine to form bile salts
    • Bile salts are modified by intestinal bacteria to form secondary bile acids
  • Pigments (bile pigments): Mainly bilirubin, also biliverdin

Formation

  1. Bile is formed at the apical membrane of hepatocytes which line the biliary canaliculi
    • Bile acids are actively transported into the canaliculi
    • This generates an osmotic gradient, driving water secretion into bile
  2. Bile flows through intrahepatic and then extrahepatic bile ducts
    • Cholangiocytes modify bile along the way, adding bicarbonate and alkalinising it
  3. Bile is stored in the gallbladder and concentrated to approximately one-fifth of its original volume
  4. During digestion, bile is secreted into the duodenum via the ampulla of Vater
  5. 95% of bile salts are reabsorbed in the terminal ileum and returned to hepatocytes via the portal vein, a process known as enterohepatic recirculation

Functions

Absorption of fats and fat-soluble compounds:

  • Lipids
  • Cholesterol
  • Fat-soluble vitamins (A, D, E, K)

Elimination of:

  • Drugs and toxins
  • Metabolic waste products (e.g. ammonia)
  • Bilirubin

Immune functions:

  • Secretion of IgG and IgA into the biliary and gut lumen

Lipid absorption


Bile salts

Bile salts are secreted into the duodenum along with pancreatic lipase.

Bile salts are amphipathic, meaning they possess both hydrophobic and hydrophilic domains. They emulsify dietary lipids into small droplets, increasing the surface area for the action of lipase.

Lipase

Pancreatic lipase hydrolyses triglycerides into:

  • Two free fatty acids
  • One monoglyceride

Free fatty acids and monoglycerides contact bile salts and form micelles.

Micelles

Micelles make contact with enterycoytes, facilitating the diffusion of lipids across the enterocyte membrane

Bile salts do not enter enterocytes themselves. They remain in the intestinal lumen and are reabsorbed in the terminal ileum.

Bilirubin excretion

  1. Haemoglobin is broken down to unconjugated bilirubin and circulates bound to albumin.
  2. In hepatocytes, bilirubin is conjugated with glucuronide to form conjugated bilirubin.
  3. Conjugated bilirubin is secreted into bile and makes its way into the bowels.
  4. In the bowels:
    • Most is reabsorbed in small bowel and undergoes enterohepatic circulation.
    • A small fraction reaches the colon.
  5. Colonic bacteria convert bilirubin to urobilinogen, which has two fates:
    • Oxidised to stercobilin and excreted in faeces โ†’ gives stool its brown colour
    • Reabsorbed and excreted renally as urobilin โ†’ gives urine its yellow colour