ICL 6.3: Hepatocellular Disease

Question 1

what is cholesterol conjugated with to get rid of it?

Answer 1

1. colic acid
2. chenodeoxycholic acid

then they’re metabolized by bacteria to deoxycholic acid and lithocholic acid

these then get reabsorbed and reconjugated so that they’re recycled up to 20 times!

Question 2

what is bilirubin conjugated with?

Answer 2

it’s conjugated with glucoronic acid to make it soluble

it’s not rebaosbred when it’s secreted

then it’s metabolized to urobilinogen by gut bacteria to urobilin and sterocobilin and at this point it can bereabsobred

Question 3

what does conjugation do to bile acids?

Answer 3

conjugation renders bile acids fully ionized at physiologic pH which makes them impermeable to cell membranes

when they’re conjugated they’re also resistant to precipitation by Ca+2 allowing large concentrations in biliary tract and small intestines

when they’re not conjugated they’re lipid soluble and can cross the cell membrane and cause problems due to decreased solubility –> soluble bile acids have antimicrobial action so they’re acting to prevent bacterial colonization that could cause diarrhea

Question 4

where is dominant absorption of bile absorption?

Answer 4

ileal bile acid transport system

apical sodium dependent cotransporter that takes conjugated bile salts back across the membrane

then once they get to the colon and the bacteria deconjugate them, they’re passively absorbed because now they’re lipid soluble

Question 5

what are the functions of bile acids?

Answer 5

1. elimination of cholesterol
2. induction of bile flow and regulation of hepatic blood flow in the liver
3. solubilization of cholesterol and heavy metal cations in the biliary tract
4. modulation of secretion in the gallbladder
5. solubilization of dietary lipids and antibmicrobila effects in the small intesitne
6. propulsive effects and secretory effects in the large intestine

Question 6

how do bile salts induce diarrhea?

Answer 6

increased presentation to the colon due to increased amount or decreased absorption

you get steatorrhea

you’ve lost the ability to deal with calcium and it doesn’t bind with oxalate more so you get kidney stones!

Question 7

how do sequestering agents deal with excess bile salts?

Answer 7

they absorb bile acids to allow for their excretion

they stimulate production of bile acids by 4x!

ultimately they decrease cholesterol levels because less bile salts means more cholesterol metabolism

help with diarrhea

Question 8

what is UDCA?

Answer 8

medication used to dissolve gallstones previously

UDCA gets secreted in the gallbladder and changes the bile acid composition so that bad bile stones dissolve! but it’s really slow dissolution so now we just take out the gallbladder

Question 9

which conditions is UDCA used to treat?

Answer 9

1. primary biliary cholangitis
2. primary sclerosing cholangitis (eh it sorta helps)
3. intrahepatic colastasis in pregnancy
4. drug induce liver injury

Question 10

30 year old male with recent cholecystectomy who has diarrhea but normal EGD/colonoscopy

how do you treat them?

Answer 10

1. antimotility agent – they’re probably taking it already…
2. rotating antibiotics – people who have bacterial overgrowth this might help but you’ll probably give them c. diff…
3. bile acid sequester*** –> this is what you give!!!!
4. fiber - probably won’t help this secretory diarrhea, they’ll just poop it all out

EGD to screen for IBD and Celiac disease

Question 11

30 year old male with an ill resection for fistulizing Crohn’s disease and now they have diarrhea

how do you treat them?

Answer 11

without the terminal ileum you can reabsorb bile salts so you get steatorrhea

rotating antibiotics – ileocecal valve keeps stuff from going back to the SI and if you get rid of it, you can precipitate bacterial overgrowth so maybe….

realistically though bile acid sequestering agents are the best

Question 12

45 year old with intermittent TUQ pain and gallstones on ultrasound

what do you do?

Answer 12

scope to make sure they don’t have an ulcer because taking out their gallstone

treat with alrpscopic cholecystectomy

UDCA is also an option if the patient isn’t fit for surgery

don’t just observe because they have a lot of pain and gallstones

MTBE dissolves gallstones when injected into the gallbladder

Question 13

what is enterohepatic circulation

Answer 13

enterohepatic circulation allows the use of a large amount of bile salts without needing to manufacture large amounds

bile salts facilitate digestion and absorption

disordered enterohepatic circulation interferes with absorption and contributes to diarrhea

disordered enterohepatic circulation contributes to oxalate absorption and without it you get oxalate stones