2 - Bile Secretions

Question 1

Objectives: Describe the composition of bile

Purpose, Production, Storage

Answer 1

• Digestion of fats, fat-soluble vitamins; Produced by hepatocytes, stored in Gallbladder

Question 2

Objectives: Describe the composition of bile

Bile Acids

Answer 2

• Primary Bile Acids synthesized in liver from cholesterol
• In intestive, converted to Secondary Bile Acids
• Conjugated to Glycine or Taurine
  
  • • Na⁺ = Bile Salts
  • > Water Soluble (at intestinal pH)
  • Ionized prevents being passively absorbed
• Amphiphathic–emulsifiers; trap fats inside micelles

Question 3

Objectives: Describe the composition of bile

Bile Pigments - Clinical?

Electrolytes

Answer 3

• Bie Pigments
  
  • Main: Bilirubin
  • Metabolite of hemoglobin; insoluble in water by made soluble when + Glucuronic Acid; secreted as salt by liver
  • Not in micelles; responsible for yellow color of bile
  • Clinical: Jaundice; due to large quantities of bilirubin; Anemia (destruction of RBCs), obstruction of bile duct/damage to liver
• Electrolytes:
  
  • Na+, Cl-, HCO₃-

Question 4

Objectives: Describe the composition of bile

Phospholipids

Cholesterol

Answer 4

• Phospholipids
  
  • ​Lecithins
  • Phospholipids normally insoluble; solubized by bile salt micelles
  • Phospholipids increase lipid solubility in micelles
• Cholesterol
  
  • Normally insoluble; solubilized by bile salts and lecithin in micelles before secreted in bile
  • Bile is primary excretory pathway for cholesterol through loss of bile salts in feces
  • *If cholesterol exceeds solubility; crystals can precipitate out; serve as seed for gallstone formation

Question 5

Objectives: Describe how enterohepatic circulation works (secretion of bile)

Absorption: Location, Transporter

Transport: RBC binding, Route, Transporter

Return to Liver: Key ion for contransport, Peptide

Excretion: Location, Pump

Answer 5

• Total pool must circulate at least twice per meal
• Absorption:
  
  • Absorption occurs at the terminal ileum (before colon) via apical sodium-dependent bile salt transporter (ASBT)
  • Deconjugate bile acids absorbed via passive diffusion
• Transport:
  
  • Bind to ileal bile acid binding protein in RBC (IBABP)
  • Bile acid enters portal blood via organic solute transporter (OST) in portal vein
• Return to Liver:
  
  • ​Hepatocytes extract bile salts with Na+ from portal blood via Sodium-taurocholate cotransporting peptide (NTCP)
• Bile Excretion:
  
  • ​Bile salts transported into bile canaliculus by ATPase-dependent bile salt export pump (BSEP) (and some MRP2)

Question 6

Objectives: How biliary secretion is regulated

Bile Independent Fraction of Biliary Secretion

Bile Dependent Fraction of Biliary Secretion

Answer 6

• Bile Independent Fraction of Biliary Secretion
  
  • Refers to volume of secretion of water and electrolytes
  • Secretin stimulates secretion of HCO₃- and water
• Bile Dependent Fraction of Biliary Secretion
  
  • Refers to quantity of bile salts secreted by liver
    
    • Amount secreted directed relates to amount of bile reabsorbed by liver
  • Bile salts and bile acids potent stimulators of bile secretion (Choleretics)
  • Bile salts and bile acids also inhibit new bile acid synthesis
• Increased secretion leads to increased return, which inhibits synthesis
• Decreased secretion leads to decreased return, which stimulates synthesis

Question 7

Objectives: Describe how the gallbladder functions

Storage

Contraction

Answer 7

• Storage:
  
  • Collects bile secreted from liver between meals
  • Concentrates bile by removing Na+, Cl-, and HCO₃- (water will follow!)
• Contraction:
  
  • Major stimulus is CCK (released in response to fat in duodenum)
  • Actions of CCK:
    
    • Contracts gallbladder; acts directly on smooth muscle; acts on vagus nerve
    • Relaxes Sphincter of Oddi
  • Major stimulus: Vagal activity during digestion

Question 8

Objectives: Describe how gallstones (Cholelithiasis) form

Two Types

Causes

Treatment

Answer 8

• Types:
  
  • Cholesterol
    
    • Most Common; composition % altered; cholesterol crystallizes
  • Pigment
    
    • Composed of calcium bilirubinate; bilirubin becomes unconjugated, which is now insoluble in bile; precipitates with Ca²⁺ to begin stone forming
• Cause:
  
  • Too much absorption of water from bile
  • Too much absorption of bile acids fro mbile
  • Too much cholesterol in bile
  • Inflammation of epithelium
• Treatment:
  
  • Removal of gallbladder - cholecystectomy
  • Bile empties slowly, but continuosly
  • Low fat diet

Question 9

Clinical: What can defects in ATPase-dependent Bile Salt Export Pump (BSEP) cause?

Answer 9

Cholestasis (reduction in or lack of bile flow)

Question 10

How is bile salt synthesis related to absorption and replacement?

Answer 10

• Bile salts not absorbed secreted in feces
• Rate of synthesis determined by rate of return to liver
• What is lost is replaced via synthesis
• If fecal loss > synthesis, total bile pool decreases