PHYS Bile Synthesis & Enterohepatic Circulation - Week 5

Question 1

Primary constituents of bile include

Answer 1

• Cholesterol – precursor of bile salts
• Bile salts – help to emulsify fats in the SI
• Lecithin – combines w bile salts to form micelles
• Electrolytes (Na, K, Ca, Cl, HCO3) & H2O – HCO3- neutralises acidic chyme in duodenum
• Bile pigments – produced by breakdown of haemoglobin.

Question 2

How is cholesterol processed by the body?

Answer 2

Conversion to bile salts or secretion into the bile.

Question 3

How can bile acid synthesis be regulated? What causes activation? Inhibition?

Answer 3

Modulation of 7a-hydroxylase enzyme. Cholesterol. Bile salts.

Question 4

How do bile acids inhibit 7a-hydroxylase?

Answer 4

Bile acids bind to FXR, causing activation of the FXR & RXR receptors -> inhibition of 7a-hydroxylase enzyme transcription -> suppression of bile acid synthesis.

Question 5

How does cholesterol activate 7a-hydroxylase?

Answer 5

Increased cholesterol detected -> 7a-hydroxylase enzyme activation -> increased bile acid synthesis -> increased bile acid secretion -> increased cholesterol uptake by the liver -> decreased plasma cholesterol levels.

Question 6

Cholelithiasis. When does it occur? Possible causes.

Answer 6

Cholesterol gallstone disease
Occurs when the cholesterol to phospholipid ratio > 1:1.
This decrease of bile acids could be the result of:
⦁ Decreased synthesis of normal, functional bile acids
⦁ Interruption and suppression of the flow of bile from the liver
⦁ Liver damage
⦁ Accumulation of abnormal bile acids & intermediaries.

Question 7

How are bile salts processed by the liver?

Answer 7

Bile is secreted from liver via bile duct -> hepatic duct.
Bile is stored in gall bladder between meals.
Gall bladder releases bile via common bile duct immediately after eating into the duodenum.
95% reabsorbed into blood & recirculated into bile
5% broken down by bacteria in the ileum (excreted in faeces).
Levels of bile salts in the exterohepatic circulation - most important stimulus for bile secretion.

Question 8

Haem breakdown pathway

Answer 8

Haem -> biliverdin -> bilirubin (as insoluble) -> bilirubin & albumin -> liver uptake -> conjugation w glucoronic acid -> conjugated bilirubin -> urobilin (stercobilin) -> excreted via urine (minor pathway)/faeces (major pathway).

Question 9

> 50um/L bilirubin may cause

Answer 9

Jaundice.