Step I Q. pathophysio for apparent jaundice in gilbert syn?

[sgsh]

Advertisement - Members don't see this ad

Q. Most individuals affected by Gilbert syndrome are asymptomatic but Jaundice becomes apparent only following stress, exertion, dehydration alcohol consumption, fasting, or infection. My question is- what is the pathophysiology by which these triggering factors cause apparent jaundice in a patient with Gilbert syndrome?

I understood that when there is infection, there will be oxidative stress (neutrophils make oxygen derived radicals to kill the bacteria) -----> thus RBC will be damaged which leads to hemolysis which eventually can lead to jaundice,Right???

But, exertion, dehydration, alcohol consumption and fasting are not the infectious casuses . How can they cause hemolysis OR apparent jaundice? Can anybody help.thanks.

 

[Silverish]

This concept was best explained by Sattar in Pathoma.
Basically, you just have a reduced number of conjugation enzymes to conjugate indirect bilirubin.
For example, Bob normally has a production of 10 units of indirect bilirubin per hour in his blood. His liver has 10 conjugation enzymes. Without stress, his liver can work to conjugate ALL of his indirect bilirubin.
Now, suppose there is a stressor (as your examples - exertion, dehydration, alcohol, fasting, etc), now Bob is making 15 units of indirect bilirubin per hour. His 10 conjugation enzymes are no longer able to handle this load. Therefore, indirect bilirubin builds up and leads to jaundice. This increased bilirubin was because the stress caused more hemolysis and more turnover of protoporphyrin --> unconjugated (indirect) bilirubin.

 

[sgsh]

Thanks Silverish.Before posting question, I already did pathoma on this topic. But, he hasn't explained how exertion, dehydration, alcohol or fasting cause hemolysis. This is what I was curious to know.If you/anyone knows- by what mechanism these stressors cause hemolysis, pls share your knowledge here.That would be of great help.

 

[Silverish]

Dehydration - a relative polycythemia, leads to increased bumping around of the RBCs along the vessels
Alcohol - disrupts plasma membranes (I've seen questions on this fact alone), including RBC's
Fasting - less energy for RBC's because they don't use ketones. Without glucose, it can't repair with its energy.
Exertion - also increased RBCs bumping around along vessels from increased cardiac output and pressure

 

[sgsh]

wao!!! Great explanation.You made it crystal clear.Thanks.

 

[worldbeater]

Yeah Silverish is right.

It occurs during stress. "UDP Glucuronyl transferase" is the enzyme that converts indirect bilirubin to direct bilirubin. In Gilbert's, you don't have enough of this enzyme, so you will have backup and increase of indirect bilirubin.