Gallstones

Question 1

What are cholesterol stones? How are they formed?

Answer 1

• Origin: gallbladder
• Composition: cholesterol
• Gallstones formed when bile is saturated w/ cholesterol so micelles and vesicles dwell in mucus layer of gallbladder
• Micelles and vesicles fuse –> multilamellar vesicles –> chol momohydrate crystals which adhere to gallbladder mucin
• Nidus for crystal growth and stone formation
• Prostaglandins induce mucin formation –> facilitates stone formation

Question 2

Normal Cholesterol Metabolism

Answer 2

• Cholesterol taken up into liver by apo B or apo E –> stored as ester, made into bile salts (by 7-alpha-hydroxylase), secreted in bile OR exported as VLDL
• Insoluble so must be excreted in bile; soluble in bile dep on lecithin (phospholipid) and bile salts in mixed micelles or vesicles
• Max solubility if bile salts + lecithin

Question 3

Risk Factors for Cholesterol Stones

Answer 3

“fat female fair forty fertile”

1- Anything that dec gallbladder contractions (less flushing of gallbladder)
- TPN (IV so no CCK release), fasting, DM (neuropathy), ocreotide, progesterone (pregnancy and women in general), cirrhosis

2- Inc cholesterol secretion or synthesis
- Age, females, obesity, pregnancy, rapid wt loss, estrogen and oral contraceptives, low HDL or high TGs (inc HMG co-reductase activity)

3- Dec bile acid synthesis
- Age, rapid wt loss, cirrhosis (not made or transported)

4- Meds

- Ceftriaxone - Ca ceftriaxone precipitate
- Clofibrate (lipid-lowering agent) - dec bile acid conc and inc free cholesterol secreted into bile

5- Family hx, genetics

- Native Americans - inc chol synthesis
- Scandinavians - inc chol secretion

Question 4

8 Protective Factors Against Cholesterol Stones

Answer 4

• Vit C
• coffee
• vegetable proteins
• poly and mono-saturated fats
• Aspirin (dec prostaglandins)
• ursodiol (bile acid to dissolve stones - make cholesterol soluble)
• give CCK w/ TPN
• Statins protective b/c dec HMG-coA reductase while other lipid lowering agent like fibric acids inc risk

Question 5

Is hyper-cholesterolemia a risk factor for cholesterol stones?

Answer 5

NO

HIGH CHOLESTEROL IN SERUM IS NOT A RISK FACTOR (but high TGs are); dep on cholesterol in bile not serum

Question 6

Black Pigment Stones (3 main cond)

Answer 6

• Origin: gallbladder
• Composition: Ca++ and unconjugated bilirubin
• Pathogenesis: unconjugated bilirubin polymerizes into insoluble polymer in a reaction catalyzed by free radicals
• Anything that inc unconjugated bilirubin is a risk
  - Cirrhosis - dec ability to conjugate
  - Hemolysis- inc prod of unconjugated
  - Chron’s - impaired enterohepatic recycling - more bile salts in colon which delay bilirubin being turned to urobilinogen by bacteria then passive reabsorption of unconjugated bilirubin in next round of liver secretions

Question 7

Brown Pigment Stones

Answer 7

• Origin: bile ducts
• Composition: mixed (chol, Ca, bilrubin, dead bacteria)
• Pathogenesis: infectious disease
• If biliary tree is exposed to duodenal bacteria and biliary stasis occurs
• Bacteria breaks down bile components

1- Lecithin –> free FAs (via bacterial phospholipase A2); so less lecithin

2- Conjugated bilirubin –> unconjugated/ insoluble bilirubin (via bacterial beta-glucuronidase)

3- Bile Salts –> bile acids and Ca++ (via bacterial deconjugase)
- See bacterial skeleton at nidus of brown stones

-Risks = after surgery or endoscopy that manipulates gall bladder or bile ducts OR hx cholangitis