Turtlez

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Is it true that bile acid resins increase hepatic cholesterol to cause gallstones?
 

MudPhud20XX

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I am not sure. Based on Kaplan biochem, it says "Cholestyramine and other drugs that increase elimination of bile salts force the liver to increase their synthesis from cholesterol, thus lowering the internal level of cholesterol in the hepatocytes." Seems like bile acid sequestrant will result in decrease hepatic cholesterol right?
 

Omar Little

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won't you have less bile salt reabsorption, which helps solubilize the bile, therefore higher chance for precipitation and thus a gallstone forming?
 

ChessMaster3000

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won't you have less bile salt reabsorption, which helps solubilize the bile, therefore higher chance for precipitation and thus a gallstone forming?
for step 1 purposes, it is gemfibrozil that causes gallstone formation. i am not sure the mechanism of this however, if someone can explain...
 

001100010010011

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I think the mechanism also involves the body making more bile acids to compensate for your lack of resorption. At a certain point your high output of bile acids may lead to gallstone formation.

I think gemfibrozil is the key drug in the category, as ChessMaster3K said.
 

Transposony

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for step 1 purposes, it is gemfibrozil that causes gallstone formation. i am not sure the mechanism of this however, if someone can explain...
Gemfibrozil causes gallstone formation due to increased cholesterol in bile.
Imbalance between bile salts and cholesterol= Gallstones.
In other words, Too much cholesterol or too little bile salts---> Gallstones.
 
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Transposony

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Is it true that bile acid resins increase hepatic cholesterol to cause gallstones?
Bile acid resins decrease bile salts pool relative to cholesterol causing Gallstones.
You have to understand that the imbalance of cholesterol:bile salt ratio is one major factor in gallstone formation.
Bile acid resins decrease enterohepatic circulation of bile salts (90% of bile salts). Although this induces formation of more bile salts from cholesterol therby lowering cholesterol (desired effect) but when the production of bile salt cannot cope with the decrease in re-absorption from the terminal ileum (decreased body pool of bile salts) it will lead to gallstone formation. It is also the cause of gallstone formation in terminal ileal disease like Crohn's.
 
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Transposony

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I am not sure. Based on Kaplan biochem, it says "Cholestyramine and other drugs that increase elimination of bile salts force the liver to increase their synthesis from cholesterol, thus lowering the internal level of cholesterol in the hepatocytes." Seems like bile acid sequestrant will result in decrease hepatic cholesterol right?
It is not the absolute decrease in cholesterol in liver but relative amount of cholesterol in bile v/s bile salts which causes gall stones.
You already know that it is the increased cholesterol in bile v/s bile salts which causes gallstone formation.
So, if the bile salts are decreased relative to cholesterol in gall bladder it will lead to gallstones.
 

ulikedaggers

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I am not sure. Based on Kaplan biochem, it says "Cholestyramine and other drugs that increase elimination of bile salts force the liver to increase their synthesis from cholesterol, thus lowering the internal level of cholesterol in the hepatocytes." Seems like bile acid sequestrant will result in decrease hepatic cholesterol right?
Right. Bile acids are usually recycled because physiologically there is limited ability to produce bile acids. Bile acid sequestrants prevent this recycling, thereby reducing the amount of inhibition of the chol --> bile acid enzyme (the name escapes me... I think it's 7-alpha hydroxylase).

So hepatic cholesterol is mobilized to form bile acids and the ratio gets messed up (as transposony said). This is one reason why you give statins with bile acid sequestrants.
 
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how does increasing lipoprotein lipase(gemfirbozil's effect) increase cholesterol to supersaturate the bile to cause gallstones?
 
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bile acid sequestrates do NOT cause gallstones, but with the deficiency of bile salts, it will cause malasbsorption. Still don't know how fibrates cause gallstones though!
 

syoung

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mechanism of action for increased gallstones due to gemfibrozil is probably not well understood; it's not that well understood how it lowers lipids; the gallstones are just a SE that's associated with gemfibrozil use.