Crohn's Disease and Gallstones (Black vs Cholesterol)

[MD22412]

Hey guys,
Rounding out near the end of the block and am stumped by a robbins questions. Basically pt has cholesterol stones and I narrow it down to:
- hyper-secretion of biliary cholesterol
- ileal resection from Crohn's

I pick ileal resection from Crohn's because I've learned that bile acids are recirculating and the lack of the bile acids creates opportunity for oversaturation by cholesterol.

Answer key differs, indicating according to Robbins that ileal involvement is a risk factor for PIGMENT STONES. I try to read up on this in robbins, but it doesn't explain why only that this is true. Can seomone explain why Crohn's predisposes to pigment stones and NOT cholesterol stones?

Any help appreciated

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[MD22412]

also, uptodate says the following: Crohn disease — The prevalence of gallstones is increased in patients with Crohn disease [75-78]. In a population based study in Sweden, for example, gallstones were detected in 26 percent of patients with Crohn disease, which was approximately twice as frequent as the general population [75]. Gallstones in patients with ileal Crohn disease (or those who have undergone ileal resection) are frequently pigment based, reflecting an increased concentration of bilirubin conjugates, unconjugated bilirubin, and total calcium in the gallbladder bile due perhaps to altered enterohepatic cycling of bilirubin [76

So I guess its billirubin cycling, however, what about ileal resection disrupting the BILE ACID enterohepatic cycling??

This baffles me

 

[Halothane27]

If I understand this question correctly. Since Crohns affects the terminal ileum most of the time, the absorption of two things are compromised ( B12 + Bile acids). Another way to look at it is, when we take a Resin drug, same is the process, less of bile acid is reabsorbed. A following of complication is that more bile has to be regenerated to accommodate for the loss. This leads to increase of gallstones in both the cases. Hopefully I am following this question.

 

[MD22412]

Hello Halothane,

Thank you for your response. Indeed Ileum is involved in absorption of B12 and bile acids. Bile acids are a derivative of cholesterol. In Crohn's disease you're right that less of bile acid is reabsorbed. More bile acids are then generated.

The question I am asking is in Crohn's disease there is an increased likelihood to develop Pigmented stones when the ileum is involved, according to Robbins. Pigmented stones are derived from calcium + bilirubin whereas cholesterol stones are derived from cholesterol oversaturation. Cholesterol stones can form when there is decreased bile acids, or when there is too much cholesterol.

To clarify: My question is, how does Crohn's predispose to producing pigment stones? (in light of the mechanism that bile acid reabsorption is altered--which would seem to suggest cholesterol stones are more likely to form)?

 

[Transposony]

Great question since it requires 2-3 step thinking. Worthy of being on the real test.

You already know that pigment gallstones occur in conditions with high heme turnover. Usual suspects are sickle cell disease, hereditary spherocytosis, and beta-thalassemia.
In Ileal disease there is malabsorption of bile acids, Vit D, B12 etc.
Vit B12 deficiency will lead to ineffective erythropoisis with lysis of erythrocytes in the marrow itself or shortly afterwards. This will lead to gradual buildup of unconjugated bilirubin causing the formation of pigment gallstones.

 

[MD22412]

Transposony,

Your explanation is beautiful. All the sources I searched hint at a disruption of the enterohepatic circulation of bilirubin. Your suggestion of B12 deficiency due to ileal involvment, leading to hemolysis (due to the macrocytic anemia) really makes sense to me. Thank you.

 

[Transposony]

Above is just one of the mechanisms of pigment stone formation in ileal disease or resection.

Here is detailed discussion on this topic.

 

[Anicetus]

Going to bump this.

So with someone suffering from crohn's where the ileum may be compromised, why can't we say the same that cholesterol stones could form due to the impaired enterohepatic recycling of bilirubin?

 

[tasar1898]

@Transposony So , crohn's can cause 1) chol gallstones due to bile salt deficiency 2) pigmented "black" gallstones due to ineffective erythropoesis and possibly increased reabsorption of bili in inflamed terminal ileum 3) ca oxalate nephrostones due to enteric oxaluria .. Is that all??

 

[yankees527]

BUMP

So in Crohn's with the ileum damaged, there is decreased enterohepatic circulation of bile acids (predisposing to CHOLESTEROL stones)

However, supposedly there is increased enterohepatic circulation of bilirubin (predisposing to PIGMENT stones)

can anyone shed some light on this?

 

[osmdj]

Hello I had same question, searched it and found that crohn's disease indeed increases enterohepatic cycling of bilirubin.


Ileal disease will prevent bile salt reabsorption and decreased bile salts in bile will increase concentration of cholesterol and bilirubin in bile and predisposes to formation of both pigment and cholesterol stones.

Normally, bilirubin is excreted in bile as conjugated, becomes unconjugated in intestine and is reabsorbed in intestine only when solubilized by bile salts (same mechanism as fat soluble vitamins and fatty acids).

Decreased bile salt reabsorption leads to increased bile salts in colon and enhance unconjugated bilirubin solubility and therefore it's absorption -> increased bilirubin that leads to pigment stones.

 

[yankees527]

Hello I had same question, searched it and found that crohn's disease indeed increases enterohepatic cycling of bilirubin.


Ileal disease will prevent bile salt reabsorption and decreased bile salts in bile will increase concentration of cholesterol and bilirubin in bile and predisposes to formation of both pigment and cholesterol stones.

Normally, bilirubin is excreted in bile as conjugated, becomes unconjugated in intestine and is reabsorbed in intestine only when solubilized by bile salts (same mechanism as fat soluble vitamins and fatty acids).

Decreased bile salt reabsorption leads to increased bile salts in colon and enhance unconjugated bilirubin solubility and therefore it's absorption -> increased bilirubin that leads to pigment stones.

Thanks

I think I figured out the confusion and it is based on location of things
So enterohepatic circulation of BILE ACIDS occurs in the ILEUM(so ileal disease wipes this out, boom cholesterol stones)

Enterohepatic circulation of BILIRUBIN occurs in the COLON (which as you said the increased solubility leads to more bilirubin absorption) and you get to pigment stones

 

[osmdj]

Thanks

I think I figured out the confusion and it is based on location of things
So enterohepatic circulation of BILE ACIDS occurs in the ILEUM(so ileal disease wipes this out, boom cholesterol stones)

Enterohepatic circulation of BILIRUBIN occurs in the COLON (which as you said the increased solubility leads to more bilirubin absorption) and you get to pigment stones

Yes that's right, bilirubin is reabsorbed in colon (can be reabsorbed in small intestine though). However fat soluble vitamins and fatty acids are reabsorbed mainly in small intenstine (is affected in crohn disease), not colon. This should explain why there is deficiency in fatty acids and fat soluble vitamins but excess in bilirubin, although all being fat soluble and reabsorbed with same mechanism