Step I eneterohepatic cycling
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what does bile have to do with folate. unless same concept applies to folate.
Dietary folate (polyglutamates) must be hydrolyzed to monoglutamates by brush-border conjugase (pteroylpolyglutamate hydrolase) enzymes in the jejunum before absorption.
Brush-border conjugase activity (and, therefore, polyglutamate hydrolysis) are inhibited by alcohol and diseases like celiac, tropical sprue, sulfasalazine etc.
Brush-border conjugase activity (and, therefore, polyglutamate hydrolysis) are inhibited by alcohol and diseases like celiac, tropical sprue, sulfasalazine etc.
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I'm still in early stages of preparation, haven't touched any qbank yet (non-US IMG here). But after studying bio (RR) and physio (BRS), I'm very surprised to hear about an enterohepatic circulation of FOLATE! I just Googled it and found this
https://www.med-ed.virginia.edu/courses/path/innes/nh/cobalmin.cfm
***Liver is a major storage site, but releases folate only into the bile for reaborption in the jejunum and ileum. This process, refered to as the enterohepatic circulation, is necessary for maintainance of plasma folate levels. Alcohol interferes with the enterohepatic circulation of folate and can lower plasma folate levels within hours***
P.S. So many typos! (I just copied and pasted)
https://www.med-ed.virginia.edu/courses/path/innes/nh/cobalmin.cfm
***Liver is a major storage site, but releases folate only into the bile for reaborption in the jejunum and ileum. This process, refered to as the enterohepatic circulation, is necessary for maintainance of plasma folate levels. Alcohol interferes with the enterohepatic circulation of folate and can lower plasma folate levels within hours***
P.S. So many typos! (I just copied and pasted)
@Transposony so let me get this straight, with ileal disease, you have decresed folate enterohepatic cycling(also seen in alcholism bc of decreases brush border conjugase activity) but with ileal disease you have increased Bilrubin enterhepatic cycling?
In ileal disease there is decreased enterohepatic cycling of folate since folate is secreted into bile and reabsorbed in jejunum and ileum.
earlier you had mentioned bc of the GI conjugases which conjugate folate from the poly to the mono form. but rehardelss bilirubin cyclying is increased but folate is reduced. weird. with ileal disease still doestn make sense how you have increased bilirubin cycling but loss of bile acids.
You can find the answer here http://forums.studentdoctor.net/thr...d-bilirubin-in-bile-pigmented-stones.1180071/
***patients with ileal disease or resection develop pigment stones as a consequence of increased spillage of malabsorbed bile acids into the colon where they solubilize unconjugated bilirubin and promote its absorption and thereby increase the rate of bilirubin secretion into the bile***
***patients with ileal disease or resection develop pigment stones as a consequence of increased spillage of malabsorbed bile acids into the colon where they solubilize unconjugated bilirubin and promote its absorption and thereby increase the rate of bilirubin secretion into the bile***
How can you solubilize unconjugated bilirubin in the colon? Isn't liver supposed to do that!
The most important pathophysiology of pigment stone formation is increased amounts of unconjugated (insoluble) bilirubin in bile that precipitates (with calcium) to form stones.
It can be due to:
1. Hemolysis
2. Ineffective erythropoiesis
3. Pathologic enterohepatic cycling of unconjugated bilirubin.
Three mechanisms of pigment stone formation in ileal disease or resection:
1. Ileal disease or resection → increased bile salts in colon → solubilize unconjugated bilirubin (from hydrolysis of conjugated bilirubin by β-glucuronidase) → prevents bacterial reduction to form urobilinogen in colon → increased enterohepatic cycling of unconjugated bilirubin → pigment stone formation.
2. Ileal disease or resection → decreased bile salt absorption → relatively decreased bile salts in GB to solubilize unconjugated bilirubin ( from hydrolysis of conjugated bilirubin by endogenous β-glucuronidase) → precipitation of unconjugated bilirubin in the bile → pigment stone formation.
3. Ileal disease or resection → Vit B12/folate deficiency → ineffective erythropoisis → lysis of erythrocytes in the marrow itself or shortly afterwards → buildup of unconjugated bilirubin → pigment gallstones.
Bottomline: Normally, bile salts get absorbed in ileum so they don't mess with the bilirubin cycling but in ileal disease they reach colon and prevents bacterial reduction of unconjugated bilirubin to form urobilinogen leading to increased absorption of unconjugated bilirubin.
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Conjugation and solubilization are two different mechanisms. (see above)
Ohhhhh ok, got it. Thanks for the perfect explanation!
@Transposony, enterohepatic cycling is actually increased, which leads to the formation of pigmented stones. The anemia contributes to it but your explanation doesnt clarify the enterohepatic theory.
Wouldn't decreasing bile salt absorption lead to increased cholesterol stones instead of pigmented stones? I remember UW saying that the deficiency of bile salts in the liver upregulates cholesterol synthesis so you have a higher ratio of cholesterol to bile salts so more cholesterol precipitates out to form stones.
Ectopic brain
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@Transposony Thanks for the detailed explanation.
I think B12 deficiency takes several years to develop, and I am not quite convinced with the ineffective erythropoesis theory. I would much appreciate if you had any reference for that theory.
I think B12 deficiency takes several years to develop, and I am not quite convinced with the ineffective erythropoesis theory. I would much appreciate if you had any reference for that theory.
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