Thread: Prehepatic jaundice

I am trying to figure out prehepatic jaundice and the blood test for bilirubin.

I understand how UNconjugated bilirubin is found in the blood in increased amounts. However, I read that ~20% of plasma bilirubin is in the conjugated form. Now, for the life of me, I cannot figure out how with a normal liver, there could be conjugated bilirubin in the blood. Every source I read simply states this as a fact, without providing any sort of mechanism.

For now I have a few theories, but no concrete answer. I hope someone can help me out. I'll keep looking, if I figure it out, I'll just post an answer to my own question.

Bilirubin is an excretion product. Its levels reflect the balance between production and excretion. Thus, there is no "normal" level of bilirubin.
However, pending metabolization (conjugation) by the liver, we expect to have "some" serum level of bilirubin (similar to creatinine), usually 0.2-1.0 mg/dL (3.4-17.1 mmol/L). At the same time, we expect this to be "unconjugated" bilirubin, waiting to be conjugated, and not conjugated bilirubin.

I will take up your query in two situations - 1. normal person and 2. prehepatic jaundice.

1. NORMAL PERSON:
What happens to conjugated bilirubin after it is formed?
It is excreted into bile and reaches intestines. Then the sequence is: conjugated bilirubin > urobilinogen > urobilin > stercobilin.

Why is conjugated bilirubin found in blood at all?
I am also equally perplexed, but put forth these thoughts:
a. The "normal" of conjugated bilirubin is 0 to 0.2 mg/dL (0 to 3.4 mmol/L). Note the lower limit - 0.
b. The "direct" bilirubin that is estimated in labs in not necessarily "conjugated" bilirubin
c. Conjugated bilirubin is water soluble. When in the gut, before it is converted to urobilinogen, it is exposed to a great array of blood vessels. Most of these are from portal vasculature. However, intestines also have "systemic" circulation. There will be systemic arterioles and venules too. Some conjugated bilirubin "may" enter systemic circulation here.

2. PREHEPATIC JAUNDICE
Just exaggerate what is happening in a normal person. The amount of unconjugated bilirubin available for liver to conjugate is increased. As long as the liver is normal, as in hemolysis, the conjugation capacity is upgraded and more conjugated bilirubin is produced.
This results in "more" conjugated bilirubin entering the gut. More conjugated bilirubin exposed to surface of absorption and more reaching systemic circulation than normal.
However, please do keep in mind that the usual upper limit is ~20%.
These are my thoughts and I encourage you to keep looking and post here if you find any further information. This could be the start of a new discussion...

Indeed this was one of my theories. My other was just that conjugated bilirubin seeps through the bile canaliculi and into the rest of the portal triad.

As for the theory you posted. The most insightful explanation of bilirubin metabolism, I found in Guyton and Hall (2006) Med Physiology. It explains that conjugated bilirubin --> intestine --> bacteria --> (~50%)urobilinogen and (~50%)unchanged. The urobilinogen is highly solube and a portion of it gets reabsorbed in the intestine (while the rest turns into stercobilin). Of this reabsorbed portion ~95% is re-excreted by the liver, while ~5% is excreted in the urine (urobilin). This is the only normal pathway I've found for "conjugated bilirubin" to end up in the blood. Although, it is not exactly what is referred to as conjugated bilirubin (bilirubin glucuronide, bilirubin sulfate), but urobilinogen. I just assume that a blood test does not discriminate between bilirubin glucuronide, bilirubin sulfate and urobilinogen as different compounds and lumps them all as "conjugated bilirubin".

Until I find out otherwise, I'll just pretend that this is the case. I'll keep digging (unfortunately I have been and have found nothing relevent yet).

Your explanation too makes a lot of sense. Together, it looks like understandable why "conjugated bilirubin" is seen in blood at all in normal individuals. Good luck with your further search on this. Hope to get your further inputs here,