Liver physiology 6: Biliary secretion and enterohepatic secretion of bile salts

Question 1

What is bile?

Answer 1

Complex lipid-rich micellar solution (water, inorganic electrolytes, and organic solutes – bile acids, phospholipids, cholesterol, bile pigments)

Question 2

How much bile do we produce a day?

Answer 2

500-600 ml a day

Question 3

Where is bile acids formed and secreted?

Answer 3

Formed in liver and secreted into canalicular which maintains hepatic bile formation which is vital for healthy liver function

Question 4

What has happened to most bile acids secreted by the hepatocyte?

Answer 4

They have been previously secreted into intestine (enterohepatic circulation)

Question 5

What are the percentage constituents of bile?

Answer 5

• 66% is bile acids
• 22% is Phospholipids
• small amounts of cholesterol, bilirubin and protein

Question 6

What can hepatic and gallbladder bile be split into?

Answer 6

• Biliary bile acids
• Fecal bile acids

Question 7

What is the function of bile?

Answer 7

• Lipid digestion and absorption
• Cholesterol homeostasis
• Excretion of lipid soluble xenobiotics / drug metabolites / heavy metals

Question 8

what are bile acids?

Answer 8

Major constituent of bile

Question 9

What synthesises bile acids?

Answer 9

Cholesterol in pericentral hepatocytes

Question 10

What is cholesterol broken down into?

Answer 10

• Cholesterol is lipophilic (fat loving)
• Broken down into Cholic Acid (CA)
• and Chenodeoxycholic acid (CDCA)
• These are primary bile acids and are water soluble

Question 11

What does the breakdown of cholesterol lead to?

Answer 11

• Primary bile acids produced
• Changes nature from lipophilic to hydrophilic

Question 12

What happens to the CA and CDCA before secreted into bile?

Answer 12

They are conjugated with glycine or taurine

Question 13

What does the conjugation of CA and CDCA do?

Answer 13

• Makes them more hydrophilic and increases acidic strength of the side chain (pKa = 5.0 unconjugated; pKa = 3.9 glycine conjugate; pKa 2.0 taurine conjugate)

Question 14

Why do CA and CDCA conjugate?

Answer 14

Conjugation decreases passive diffusion of bile acids across cell membranes so traps them within the lumen of the small intestine so they can do their job

Question 15

What enzyme aids the conversion of cholesterol into CA and CDCA?

Answer 15

CYP7A1 so now they are primary bile acids

Question 16

What happens as bile moves down the gut?

Answer 16

As bile moves down gut into colon it gets de-hydroxylated by intestinal bacteria into:
- Deoxycholic acid and lithocholic acid (SECONDARY BILE ACIDS)

Question 17

What enzyme aids conversion of primary bile acids into secondary bile acids

Answer 17

Enzyme = 7alpha-dehydroxylase

Question 18

What does it mean that bile acids are amphipathic?

Answer 18

Amphipathic (hydrophilic and hydrophobic parts) – reduce surface tension and aid emulsification

Question 19

How are fats digested?

Answer 19

1. Fat consumed
2. Motility breaks them down slightly into emulsion droplets
3. Bile acids and phospholipids coat the emulsion droplets – stop them returning to a larger fat globule
4. Hydrophilic end pointing outwards
5. Colipase binds onto the surface of the emulsion droplet
6. This helps anchor lipase to the surface as well – forms close association between lipase and TG
7. Begins to break down TGs into monoglycerides and free fatty acids
8. Re-associate together to form micelles (bout 200 times smaller)
9. Micelles constantly form and breakdown (equilibrium)
10. Release contents and becomes free to diffuse into the enterocyte

Question 20

How are fats absorbed?

Answer 20

1. Reform TGs
2. To ER and Golgi where they are packaged into vesicles – chylomicrons
3. Then exocytosed into the lacteals of the lymphatic system
4. Then general circulation
5. Broken down by lipoprotein lipase to release TGs
6. Form monoglyceride and free FA which are then taken up into cells to be utilised or stored

Question 21

What are some functions of bile acid?

Answer 21

• They induce the bile flow and secretion of biliary lipids
• Digestion of dietary fats
• Facilitates protein absorption
• Cholesterol homeostasis
• Prevents calcium gallstones and oxalate renal stones

Question 22

What happens to bile acids during the fasted state?

Answer 22

• Bile acids travel down the biliary tract from the liver to the gallbladder where they are concentrated x10 because the Sphincter of Oddi is contracted.

Question 23

What happens when we eat and the effect on bile acids?

Answer 23

When fats are entered into the duodenum, this causes the release of CCK (cholecystokinin) to be released from duodenal mucosa
- CCK – relaxes SO (sphincter of Oddi) and contracts GB releasing concentrated solution of mixed micelles (BA, PL, cholesterol)

Question 24

Where are bile acids then abosrbed?

Answer 24

• Due to conjugation they are not absorbed until the terminal ileum
• They are actively transported via the sodium-bile acid transporter (ASBT) in the terminal ileum back into the blood
• The bile acids then re-enter the liver via portal circulation
• and then taken up by hepatocyte and secreted into biliary canaliculi

Question 25

How many cycles of bile acid do we have per meal?

Answer 25

2-3 cycles of bile acid going round per meal

Question 26

How is FGF19 produced?

Answer 26

• The secondary bile acids enter ileum and are synthesised with Farnesoid X receptor to produce FGF19

Question 27

How does the production of bile stop (negative feedback loop)

Answer 27

• The synthesis of FGF-19 – an endocrine polypeptide molecule inhibits CYP7A1 (cholesterol 7𝛼 hydroxylase) which breaks down cholesterol into bile acids