BOTH Increase amount of UNconjugated bilirubin in Bile = pigmented Stones

[musashivii]

According to UW, pigmented stones is caused from conditions that increase the amount of unconjugated bilirubin in bile. Some examples it gave were

1) Biliary tract infection

2) Chronic hemoloytic anemia (e.g.: Sickle cell anemia)

3) increase enterohepatic cycling of bilirubin (Crohn's Disease)


For point 1: I understand that microbe in the bile duct can produce b-glucuronidase, leading to deconjugation of the conjugated bilirubin back into unconjugated bilirubin in bile.


I don't understand how point 2 and 3 can lead to increased unconjugated bilirubin in bile. I thought the only way that bilirubin can get into bile is after it gets conjugated in the liver normally. The following two points are unsure for me. Please correct me.

For point 2: increase unconjugated bilirubin due to hemolysis also increase conjugated bilirubin, which then increase excretion of conjugated bilirubin into bile/gut..later to be converted into urobilinogen. Urobilinogen will then be reabsorb back into the liver to be re-excreted into the bile [do we consider this re-excreted urobilinogen same as unconjugated bilirubin?]


For point 3:[ NCBI/pubmed: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4077498/] stated that patients with Crohn’s disease is that 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)

Is this unconjugated bilirubin they referring to urobilinogen? Isn't unconjugated bilirubin already lipid-soluble and is readily be absorbed? Why would bile help aid the increase absorption?



A side question that I always wonder is why does our body need to resorb bilirubin? I understand we need to reabsorb bile acids to aid in fat absorption , but why bilirubin?


Thank you guys!

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[musashivii]

Bump.

 

[HereWeGo21]

Bump.

Hey man. I was confused about this too at some point.

What happens is that the unconjugated bilirubin does NOT enter the gallbladder from the hepatocyte.

Rather, it enters directly from the blood supply to the gallbladder. So, the gallbladder needs blood like any other tissue. When there's a lot of unconjugated bilirubin in the blood, that unconjugated bilirubin extravasates in the GB, enters the GB tissue, eventually enters the lumen, and precipitates.

 

[HereWeGo21]

To answer some of your other questions:
In Crohn's, you have failure to reabsorb bile acids in the terminal ileum, due to inflammation.
So, bile acids are delivered more distally.

Now, important point: the purpose of bile acids is NOT to increase the solubility of the GI contents. Rather, the point is simply to EMULSIFY. So, unconjugated bilirubin might be sitting in the GI tract, as lipid-soluble as ever. But still, it's surrounded by a huge globule of fat. So, there's no way that unconjugated bilirubin will be absorbed, simply because the GI doesn't have access to it.

That's where bile acids come in. They're amphiphilic, which lets them convert a huge fat globule into many smaller micelles. The point here, is, again, NOT to increase solubility of anything, but rather to increase SURFACE AREA, such that those things which were soluble all along can now be reabsorbed. So, with distal delivery of bile acids in Crohn's, you'll have more reabsorption of unconjugated bilirubin.

Now, finally, you asked: why is there unconjugated bilirubin in the GI anyway? Well, I haven't seen too much on this, but I think in one World question they mentioned that gut bacteria can DECONJUGATE bilirubin. So, this would answer your question about that. It seems like this might only be clinically relevant in Crohn's, and other cases of excess distal bile acid delivery (cholestyramine, maybe). In this case, fats containing deconjugated bilirubin are emulsified, and the unconjugated bilirubin is absorbed.