Bile acids

Question 1

What are the bile acids and their solubilities?

Answer 1

——liver—————-

Cholesterol is the least soluble.

Primary bile acids are the most soluble (hydroxylation)

1. Cholic acid
2. Chenodeoxycholic acid

Then they can have addition Taurine or Glycine group added to decrease pka even more. aka (conjugation)

1. Taurocholic acid
2. Glycocholic acid
   or
3. Taurochenodeoxycholic acid
4. Glycochenodeoxycholic acid

Intestines—–bacterial transformation—- ——————

(deconjugation)
1. Cholic acid
2. Chenodeoxycholic acid

(dehydroxylation)
1. Deoxycholic acid
2. Lithocholic acid

Question 2

What is CYP7A?

Answer 2

It synthesizes bile acids from cholesterol.

Cholic acid product will inhibit CYP7A.

Cholesterol activates CYP7A.

The whole point is to make the cholesterol more soluble by lowering pKa.

Question 3

Describe the enterohepatic circulation of bile acids.

Answer 3

In the liver, bile acids are formed from cholesterol by CYP7A. All bile acids that leave the liver are conjugated. (BSEP - bile acid export pump)

It travels in the common hepatic duct and travels up the cystic duct to be stored in gallbladder.

Upon stimulation by CCK, bile is released from the gallbladder into the common bile duct which travels through the sphincter of oddi in the wall of the duodenum and emulsifies fat.

Then it travels and at the terminal ileum, most bile is reabsorbed by the (ASBT + OSTalpha,beta) hepatic portal vein and bile salts return to liver. (NTCP from sinusoidal space to hepatocyte)

5% of bile salts are lost in feces.

Question 4

What are the bile acid transporters in the enterohepatic circulation?

Answer 4

NTCP (sodium taurocholate cotransporting polypeptide): brings both sodium and bile acid into the hepatocyte from the sinusoidal space

BSEP (bile acid export pump): using ATP exports bile acids into the canaliculus.

ASBT - apical sodium bile acid transporter - bring sodium and bile acid into the ileal cell.

OSTaB - organic anion transporting polypeptides: brings the bile acid from the basal side into the portal vein.

Question 5

Describe Cholelithiasis

Answer 5

Occurs when more cholesterol enters the bile than can be excreted, the concentration of cholesterol in bile is too high, it may precipitate and lead to gallstone disease.

————–Causes————–
Severe ileal disease - reduce bile so more cholesterol will be secreted into bile.

Obstruction of bile duct - if the cholesterol stays in place long enough

Severe hepatic dysfunction/ hepatic hypersecretion - interfere with any of the enzymes making bile acids. Leads to more secretion of cholesterol.

LITH genes - stone genes, propensity to form gallstones

• ——morphologic features———
  1. enlarged hepatocytes
  2. enlarged Kupffer cells which uptake bile acid
  3. dilated canallicular spaces
  4. apoptotic cells

Question 6

What three factors of bile composition increases gallstone formation?

Answer 6

1. increased cholesterol concentration
2. decreased lecithin (phospholipid)
3. decreased bile salt

You are essentially increasing the concentration of cholesterol in bile, that is all.

Question 7

What are the three types of biliary obstructions and their consequences

Answer 7

Cystic bile duct - painful gallbladder contraction

Common bile duct - no bile will be released into duodenum

• leads to Steatorrhea: the inability to digest fats
• Jaundice: failure to excrete bilirubin

Pancreatic duct: no release of bile or pancreatic secretions into duodenum.
This will lead to severe malnutrition as you cannot digest food.

Question 8

What are BAS (bile acid sequesterins useful for)?

Answer 8

If you sequester bile acids and prevent their reabsorption, the bile acid levels will reduce.

This means the liver needs to take more cholesterol from the blood stream to make more

Questran, Welchol, Colestid: all lower high cholesterol levels.