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! (http://www.flickr.com/photos/52587958@N00/2653236631/)
Tagsacute leukemia acute lymphoblastic leukemia acute myeloid leukemia acute promyelocytic leukemia Add new tag anemia b cells blood smear bone marrow brain tumors carcinoma cases chronic myelofibrosis chronic myeloid leukemia chronic myeloproliferative disorders coagulation cortisol cytochemistry cytogenetics essential thrombocythemia heart hemophilia immunology infection inflammation kaplan kidney laboratory tests lymphocyte lymphocytes lymphoma macrophages neoplasia neutrophil normal photoblog polycythemia vera red blood cells red cells sickle cell anemia skin squamous cell carcinoma stains student questions t cells
- preetam said thank u very much sir……
- Kristine said Thanks, Karen! So glad you’ve found it helpful
- Karen said I’m currently a med tech/cls student studying for the ASCP Medical Technology generalist licen...
- Kristine said Good question, Aghara – here’s a post that addresses that very issue....
- aghara mahesh said how to differentiate between activated lymphocyte and monocytic precursor and mature monocyte ?
- Kristine said Hi Sashi – Yes – that is all correct!
- LA TESHIA HENDERSON said Thanks a bunch
- Palina said I am in awe. Thank you for such a thorough, yet simple explanation. Can’t wait to see more.
- Sashi said Great answer, thank you. Just for clarification. Thrombin converts factor XI to XIa and VIII to VII...
- Kristine said Hi Mishl – Yes, exactly! Most labs will use the automated counter for all samples, and then ma...
- Kristine said Hi Chris – You hit on a good point, which is that sometimes, pathology terms are used loosely...
- bobby flay said Christine is the hottest pathologist I’ve ever seen. And so smart too. I periodically read pat...