infectious bacteria that affect the proximal colon
- Salmonella
- yersinia -> pseudoTB
- TB
Infectious causes of diarrhea
- damage epithelial cells: Rotavirus, Norwalk virus (both sm. intestine)
- PREformed toxins: vibrio, staph aureus, clostridium perfringens
- toxigenic: E. coli, shigella
bacteria that affect the distal colon
- shigella
- E coli *risk HUS as complication! (can be deadly)
- Campylobacter
Liver Cirrhosis signs (triad)
- diffuse involvement
- fibrosis
- regenerative nodules (abnormal)
(gross: hard, nodular, atrophic liver)
Bile acid uses
- cholesterol catabolism
- stimulate bile flow
- absorb dietary cholesterol (as mixed micelle w/ lecithin in gut)
- cholesterol solubilization
- Treatment of gallstones, SIBO, primary biliary cirrhosis…
cholesterol 7a-hydroxylase
Enzyme that converts cholesterol to 1st intermediate of bile acid synth.
= rate limiting step for bile acid synthesis
* Inhibited by bile acids
* stimulated by cholesterol
Bile acid synthesis (steps, results)
- @ Liver: Cholesterol –> 1st intermed by cholesterol 7a-hydroxylase
- @ intestinal lumen: 2 different intermediates modified => bile acids (cholic & chenodioxycholic acids)
- @ liver: bile acids conjugated & stored
Liver transporters for Bile Acids
- NTCP & OATP: transport bile salts from plasma into hepatocyte
(“Na+ Taurocholate Cotransporter” & “Organic Acid Transporter”) - BSEP: transports bile salts from hepatocyte into bile canaliculus
Intestinal bile acid transporter
ASBT: “Apical Sodium-dep. Bile Transporter”
transports bile salt w/ Na+ into terminal ileocyte from gut lumen
(for recycling back to liver, 95%)
3 states of cholesterol (w/ bile acids)
- Mixed Micelle: bile acid clump w/ lecithin-cholesterol vesicles in middle; = stable & soluble.
- Vesicle: just lecithin & cholesterol; ~”metastable”
- Cholesterol crystals: only cholesterol, precipitates => gallstones
Causes of gallstones
- high lipids
a) increased cholesterol intake/secretion
b) decreased bile salts - short nucleation time
Chenodeoxycholic acid vs. Ursodeoxycholic acid
Chenodiol: decrease cholesterol secretion, & increases bile acid pool at HIGH doses. *SE: hepatoxicity, diarrhea, high serum cholesterol
#1 Ursodiol: same mech as chenodiol + increase nucleation time & decrease crystal precipitation. *NO SEs! (hepatoprotective bc inhibits apoptosis)
Therapeutic uses of Ursodiol
- cholelithiasis (gallstones)
- primary biliary cirrhosis
- Intrahepatic cholestasis of pregnancy
- SIBO (sm intestine bacterial overgrowth)
SIBO (Small Intestinal Bacterial Overgrowth)
diarrhea/steatorrhea; likely to cause stasis of small bowel
=> vit B12 deficiency & decreased bile salt absorption/recycling
