Here’s a little question to see if you remember the different causes of conjugated and unconjugated bilirubinemia.

While examining the gums of a 25 year old patient, a yellowish discoloration of the oral mucosa and sclera is noted.  Laboratory tests show a significant increase in unconjugated bilirubin.  Which of the following disorders is most likely the cause of this patient’s abnormalities?

A. A stone in the bile duct
B. Carcinoma of the head of the pancreas
C. Pancreatic pseudocyst
D. Sickle cell disease
E. Hepatocellular carcinoma

Let’s review a little before we get to the question.

Bilirubin is a breakdown product of heme (which, in turn is part of the hemoglobin molecule that is in red blood cells). It is a yellow pigment that is responsible for the yellow color of bruises, and the yellowish discoloration of jaundice.

When old red cells pass through the spleen, macrophages eat them up and break down the heme into unconjugated bilirubin (which is not water soluble). The unconjugated bilirubin is then sent to the liver, which conjugates the bilirubin with glucuronic acid, making it soluble in water. Most of this conjugated bilirubin goes into the bile and out into the small intestine. (An interesting aside: some of the conjugated bilirubin remains in the large intestine and is metabolized into urobilinogen, then sterobilinogen, which gives the feces its brown color! Now you know.)

So: if you have an increase in serum bilirubin, it could be either because you’re making too much bilirubin (usually due to an increase in red cell breakdown) or because you are having a hard time properly removing bilirubin from the system (either your bile ducts are blocked, or there is a liver problem, like cirrhosis, hepatitis, or an inherited problem with bilirubin processing).

The lab reports the total bilirubin, and also the percent that is conjugated vs. unconjugated. If you have a lot of bilirubin around and it is mostly unconjugated, that means that it hasn’t been through the liver yet – so either you’ve got a situation where you’e got a ton of heme being broken down (and it’s exceeding the pace of liver conjugation), or there’s something wrong with the conjugating capacity of the liver (like a congenital disorder where you’re missing an enzyme necessary for conjugation – for example, Gilbert syndrome). If you’ve got a lot of bilirubin around and it’s mostly conjugated, that means it’s been through the conjugation process in the liver – so there’s something preventing the secretion of bilirubin into the bile (like hepatitis, or biliary obstruction), and the bilirubin is backing up into the blood.

Back to our question. Let’s go through each answer and see what kind of hyperbilirubinemia these disorders would cause.

A. A stone in the bile duct – if big enough, a stone here could block the excretion of bilirubin into the bile. The bilirubin would already be conjugated, so this would be a conjugated bilirubinemia.

B. Carcinoma of the head of pancreas – this could also cause biliary obstruction, similar to A. (An important aside: it’s nice when pancreatic carcinomas announce themselves this way, because it may allow for earlier detection of the tumor. Unfortunately, this is uncommon. Pancreatic adenocarcinoma is usually silent until the tumor is very large and possibly metastatic.)

C. Pancreatic pseudocyst – same idea as A and B.

D. Sickle cell disease – Sickle cell anemia is a type of hemolytic anemia. It could be a cause of unconjugated bilirubinemia, if the hemolysis is massive enough. If it’s just a low level of hemolysis, the liver could probably keep up, and you’d get a conjugated hyperbilirubinemia.

E. Hepatocellular carcinoma – this would fall into the category of blocking excretion of bilirubin. The bilirubin would already be conjugated – so this would be a conjugated hyperbilirubinemia.

So: since A, B, C and E produce only conjugated hyperbilirubinemia, the answer is D, sickle cell disease.

Image credit: Compound Eye – in Practical Photography now! (

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76 Responses to Conjugated vs. unconjugated bilirubinemia

  1. ebylicia says:

    Awesome 10x helped alot

  2. Maggie says:

    A very good question. Kristine’s explanation above helps to clarifying why D is the correct answer and not E which is what I thought of initially. Thanks.

  3. Abrar Ali Katpar says:

    Nice explanation.

  4. Nkiru Abanaka-Bassey says:

    Good explanation!!

  5. Nkiru Abanaka-Bassey says:

    Very Good one!!

  6. Godwin Onah says:

    This is Pathophysiology made simple.

  7. christian says:

    wow awesome explanation, thanks !!!

  8. mike says:

    I appreciate this explanaion.I though it was E
    By now I agree

  9. Cathy says:

    Dude, thank you so so much, I have an exam in 48 hrs xoxoxoxoxox

  10. Kristine says:

    Yay! Glad it helped :)

  11. sancha says:

    Thankyou for this very clear explanation, it helped a lot!

  12. Sunil Nandwani says:

    I wish to buy Complete Haematopath guide/Clot or bleed books. Anyway I can do that? Thanks

  13. Kristine says:

    Yes! The Complete Hematopathology Guide is sold here, and the Clot or Bleed book is sold here. You can get both together as a set and save $9.50.

  14. elmer says:

    This is very helpful explanation. Thank you very much.

  15. FQ says:

    Helped alot thanx <3

  16. Shahariar Shuvo says:

    Nice explanation

  17. Priyanka says:

    Thank u soo much. …

  18. madzz says:

    Well explained…..
    Now cleared from the confusion of cb nd ucb.

  19. Mukul says:

    very clear and simple explanation so helpful

  20. makuru charles konna says:

    amazing explanatn

  21. Sara says:

    Thanks,from youre brilliant explanation.

  22. a smith says:

    great posting!

  23. Javid says:

    Excellent explanation

  24. Claudia says:

    Very helpful explanation, makes sense! Thanks!!

  25. Obianuju says:

    Amazing explanation.

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