Table of contents
Estimated reading time: 6 minutes
Introduction
- Synthesis of bile : Liver (0.6-1 L/d)
- Storage of bile : Gall bladder (~50 mL)
- Colour : Golden yellow (Bile pigments: Bilirubin, Biliverdin)
Functions
| Fat digestion & absorption | Bile acids ↓ Fat emulsification ↓ Fat absorption |
| Excretion of waste products |
Composition
Liver: Bile synthesis
↓
Gall bladder: Concentration of bile by active absorption of water, sodium chloride and bicarbonate
↓
| Components | Hepatic bile | Gallbladder bile | |
| Water | 97.5% | 92% | |
| HCO3– | 28 mEq/L | 10 mEq/L | |
| Na+ | 145 mEq/L | 130 mEq/L | |
| Cl– | 100 mEq/L | 25 mEq/L | |
| Bile salts | 1.1 gm/dL | 6 gm/dL | |
| Bilirubin | 0.04 gm/dL | 0.3 gm/dL |
Components
Bile pigments
- Any of colouring matter of bile
- Byproduct of heme degradation : Biliverdin, Bilirubin
Bilirubin metabolism & excretion
| Reticuloendothelial system | Hemoglobin ↓ Heme (Porphyrin) ↓ Heme oxygenase Biliverdin ↓ Biliverdin reductase Bilirubin (Unconjugated): Free bilirubin ↓ |
| Blood | Unconjugated bilirubin : Water insoluble → Albumin bound ↓ Albumin-bound bilirubin in sinusoidal blood passes through endothelial cell fenestrae to reach hepatocyte surface ↓ Facilitated and simple diffusion Hepatocellular uptake |
| Liver | ↓ Unconjugated bilirubin ↓ Glutathione-S-transferases (Ligandins) bound bilirubin ↓ UDP-glucuronosyl transferase (UDP-GT): UGT1A1 Bilirubin glucuronides (Conjugated bilirubin) → Water soluble ↓ MRP2 Transported across canalicular membrane into bile ↓ Small intestine |
| Small intestine | ↓ Conjugated bilirubin Conjugated bilirubin is not reabsorbed by intestinal mucosa due to its hydrophilicity & increased molecular size |
| Large intestine | ↓ Conjugated bilirubin ↓ ↓ Gut bacteria: β-glucuronidases Urobilinogen ↓ 80% Stercobilinogen ↓ Stool ↓ Oxidation (Air) Stercobilin Sterecobilinogen is excreted in stool |
Unconjugated bilirubin does not reach gut Except Neonates, Ill-defined alternative pathways, Severe unconjugated hyperbilirubinemia
Only conjugated bilirubin can be excreted in urine → Very minor amount → Bilirubin can’t be detected in urine
Urobilinogen secreted in urine in significant amount → Urobilinogen can be detected in urine
Total serum bilirubin level = 0.3-1.3 mg/dL
Unconjugated (Indirect) bilirubin
- Serum unconjugated bilirubin = 0.2-0.9
- Water-insoluble → No renal excretion
- Albumin bound
- Only unconjugated bilirubin can cross BBB into CNS
Conjugated (Direct) bilirubin
- Serum conjugated bilirubin = 0.1-0.3
- Water-soluble → Renal excretion
- Kidney: Overflow valve for conjugated bilirubin
- Can’t cross BBB
Bile acids
Acids derived from cholesterol
Cholesterol
↓ 7α-hydroxylase : Rate-limiting enzyme
Primary bile acids
- Cholic acid
- Chenodeoxycholic acid
↓ Conjugation: Glycine, Taurine (3:1)
Bile salts
- Glycocholic acid
- Taurocholic acid
- Glycochenodeoxycholic acid
- Taurochenodeoxycholic acid
↓
| ↓ 90-95% Enterohepatic circulation Reabsorption of conjugated bile acids (bile salts) into blood at terminal ileum by active Na+-K+ ATPase ↓ Portal blood ↓ Venous sinusoids ↓ NTCP, OATPs Absorption into hepatic cells ↓ Resecretion into bile | ↓ 5-10% Large intestine: Colon ↓ Colonic bacterial enzymes: Deconjugation Secondary bile acids (Deoxycholic acid, Lithocholic acid) ↓ Majority: Enterohepatic circulation Reabsorption of secondary bile acids (unconjugated) into blood at colon by passive nonionic diffusion ↓ Portal blood ↓ Venous sinusoids ↓ Absorption into hepatic cells ↓ Resecretion into bile |
Bile acid reabsorption
| Reabsorption of conjugated bile acids (bile salts) into blood can occurs only at terminal ileum by active Na+-K+ ATPase ↓ Role: 90-95% of total bile acid reabsorbed | Reabsorption of unconjugated bile acids (primary or secondary bile acids) into blood can occur at jejunum, ileum & colon passively ↓ Role: 5-10% of total bile acid reabsorbed |
Bile acid pool
- Bile acid pool size: 4 gm
- Bile acid pool recycles twice per meal and 6-8 times per day
- Bile acid make entire circuit some 17 times before being carried out in feces
- Bile acids fecal excretion : 0.5 gm/day
- Bile acid hepatic synthesis: 0.5 gm/day (Maximum: ~5 gm/day)
Function
| Emulsifying agent ↓ Fat digestion | Bile salts: Detergent action on fat particles in food ↓ Emulsification : Bile acids, Lecithin ↓ Surface tension of particles ↓ Agitation Emulsified lipid: Fat globules breaks into minute sizes |
| Fat absorption | Fatty acids, Monoglycerides, Cholesterol ↓ Bile salts Micelles (Molecular aggregate) |
| Promotes bile flow |
Clinical aspect
| Defective process | Defect | Disease |
| Hepatic bile synthesis | ↓ Hepatic bile synthesis | Liver cirrhosis |
| Biliary secretion | ↓ Bile secretion | Primary biliary cirrhosis Biliary obstruction |
| Maintenance of conjugated bile acids | ↓ Conjugated bile acids | Bacterial overgrowth syndrome |
| Reabsorption of bile acids | ↓ Ileal reabsorption of conjugated bile acids | Crohn’s disease Ileal resection |
Bile secretion & storage
Bile synthesis in liver
↓ cAMP dependent
Continuous hepatic secretion of bile at 40 mL/hr
↓
| During fasting i.e. between meals ↓ ↑↑ Resistance to bile flow through sphincter of Oddi ↓ Bile flow diverted through cystic duct into gallbladder ↓ Bile storage in gall bladder (~50 mL) ↓ Concentration of bile | After feeding ↓ ↓↓ Resistance to bile flow through sphincter of Oddi ↓ Hepatic bile not diverted to gall bladder → Hepatic bile enters duodenum through CBD + ↓ CCK Rhythmical contraction of gall bladder ↓ Bile (concentrated) released from gall bladder ↓ Bile enters duodenum through CBD |
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