Components of Bile
Bile is primarily composed of bile salts, phospholipids (mainly lecithin), cholesterol, proteins, and bilirubin, with bile salts being the predominant component ranging from 3-20 mM concentration depending on fed or fasted state. 1
Primary Components of Bile
Bile Salts/Acids
- Bile salts are the end products of cholesterol metabolism and are the main functional components of bile 2
- Concentration ranges from 3 mM (fasted state) to 20 mM (fed state) in the small intestine 1
- Common bile salts include:
- Sodium glycodeoxycholate
- Sodium deoxycholate
- Taurocholate
- Taurodeoxycholate
- Cholate
- Glycocholate 1
- Bile acids are synthesized in the liver from cholesterol and conjugated with glycine or taurine before secretion 2
- Conjugation makes bile acids impermeable to cell membranes and allows high concentrations to persist in bile 3
Phospholipids
- Phospholipids constitute a significant portion of bile, with phosphatidylcholine (lecithin) being the predominant type (>96%) 4
- Phospholipids can provide a protective effect when combined with bile salts 1
- The presence of lecithin can reduce the cytotoxicity of bile salts like sodium deoxycholate 1
Cholesterol
- Unesterified cholesterol is a major component of bile 4
- Hypersecretion of hepatic cholesterol into bile is the primary pathophysiological defect in cholesterol gallstone disease 4
- The molar concentrations of cholesterol, bile salts, and lecithin determine the solubility of cholesterol in bile 2
Bilirubin
- Bile contains bilirubin conjugates, also known as lipopigments 4
- Bilirubin has been shown to inhibit calcium carbonate precipitation in gallbladder bile 5
- It can form complexes with albumin and interfere with calcium carbonate precipitation 5
Proteins
- Bile contains various proteins, with over 222 unique proteins identified in human gallbladder bile from a cholesterol stone patient 6
- Albumin is one of the proteins present in bile that can interact with bilirubin 5
Physiological Functions of Bile Components
Bile salts are essential for:
Phospholipids contribute to:
Clinical Significance of Bile Components
- Bile salt toxicity is well documented, with different bile salts showing varying levels of cytotoxicity 1
- Disruptions in bile formation and flow can lead to cholestasis, jaundice, pruritus, and liver damage 7
- Genetic defects in bile transporters can lead to various cholestatic disorders, including Progressive Familial Intrahepatic Cholestasis (PFIC) 7
- Ursodeoxycholic acid (UDCA) is commonly used to treat cholestatic conditions by changing bile composition from hydrophobic to more hydrophilic 7
- Bile acid sequestrants like cholestyramine can be used to treat bile acid reflux by forming an insoluble complex with bile acids in the intestine 8
Bile Transport Mechanisms
- Bile acids undergo enterohepatic circulation, being absorbed from the small intestine and recycled multiple times before excretion 2
- The ileal bile acid transporter (IBAT) is responsible for bile acid reabsorption in the terminal ileum 1
- Disruption of the enterohepatic circulation can be therapeutic in certain conditions, such as using IBAT inhibitors (maralixibat, odevixibat) to treat cholestatic pruritus 1