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|MainCategory=Pathophysiology, Physiology
|MainCategory=Pathophysiology, Physiology
|SubCategory=Gastrointestinal
|SubCategory=Gastrointestinal
|Prompt=A 45 year old man admitted to the hospital for work-up of severe painless jaundice and icterus is found to have a massive obstructive pancreatic head mass almost completely closing the bile duct lumen. Which of the following patterns would you expect in this patient?
|Prompt=A 21 year old man is admitted to the hospital for dizziness, shortness of breath, and jaundice several hours after he took 2 tablets of aspirin. The patient explains that this is the first time he has such an episode and that he has only been to the hospital once before for severe anemia. The patient also reports family history of jaundice. Work-up reveals a hemoglobin of 6.7 g/dL with blood smear shown below. Which of the following patterns would you expect in this patient?
 
 
[[Image:WBRjaundice.jpg|550px]]




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Considering the patient's presentation, one would expect obstructive type jaundice. Obstructive jaundice is characterized by direct or conjugated hyperbilirubinemia since the conjugation mechanisms are not affected rather the excretion of conjugated bilirubin through bile is inhibited. As conjugated bilirubin builds up it increases in the blood. As it is water soluble (compared to unconjugated bilirubin which is not) it is excreted in large amounts in the urine, giving the urine a darker color. Urine urobilinogen is a product of bile recycling in the intestines. As the obstruction hinders bile release into the intestine, one would expect urine urobilinogen levels to decrease. Similarly, fecal stercobilin is related to bile content of the fecal material, so one would also expect the stercobilin levels to decrease and stool color to become much lighter.
The patient's presentation is typical for hemolytic anemia in the context of glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD is an enzyme catalyzing the rate limiting step of the pentose phosphate pathway. It transforms glucose-6-phosphate to 6-phosphogluconolactone while restoring NADPH needed to reduce glutathione. In patients with G6PD deficiency, NADPH cannot be restored in RBCs leading to glutathione depletion and susceptibility of RBCs to oxidative damage brought on by drugs and other substances notably fava beans (hence the name favism). Hemolysis in general leads to elevation in indirect unconjugated bilirubin which is not very water soluble. This fact is important since it explains the absence of bilirubin in the urine as water insoluble substances cannot be excreted by the kidneys. In parallel, conjugation of the excess indirect bilirubin occurs in the liver leading to increase excretion and a secondary increase in fecal stercobilin. Urine urobilinogen is an indicator of bile reabsortption, thus as bile excretion increases, urobilinogen increases as well.
 


Learning objective: Obstructive jaundice is characterized by direct (conjugated) hyperbilirubinemia with increase in urinary bilirubin and decrease in urobilinogen.
Learning objective: Hemolytic jaundice is characterized by indirect (unconjugated) hyperbilirubinemia with absent urinary bilirubin and increase in urobilinogen.




References:
References:


Diagnosis of obstructive jaundice. Calif Med. 1970;112(5):44-58.
Beutler E. G6PD: population genetics and clinical manifestations. Blood Rev. 1996;10(1):45-52.


Le T, Bhushan V. First Aid for the USMLE Step 1 2014. McGraw-Hill Medical; 2014.
Le T, Bhushan V. First Aid for the USMLE Step 1 2014. McGraw-Hill Medical; 2014.
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|AnswerEExp=This pattern is typical of hemolytic type jaundice.
|AnswerEExp=This pattern is typical of hemolytic type jaundice.
|RightAnswer=B
|RightAnswer=B
|WBRKeyword=Obstructive jaundice, Bilirubin,
|WBRKeyword=Hemolytic jaundice, Bilirubin, unconjugated hyperbilirubinemia
|Approved=No
|Approved=No
}}
}}

Revision as of 07:52, 24 October 2013
Author [[PageAuthor::Rim Halaby, M.D. [1]]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Pathophysiology, MainCategory::Physiology
Sub Category SubCategory::Gastrointestinal
Prompt [[Prompt::A 21 year old man is admitted to the hospital for dizziness, shortness of breath, and jaundice several hours after he took 2 tablets of aspirin. The patient explains that this is the first time he has such an episode and that he has only been to the hospital once before for severe anemia. The patient also reports family history of jaundice. Work-up reveals a hemoglobin of 6.7 g/dL with blood smear shown below. Which of the following patterns would you expect in this patient?



]]

Answer A AnswerA::A
Answer A Explanation AnswerAExp::This pattern is usually not seen.
Answer B AnswerB::B
Answer B Explanation AnswerBExp::This pattern is typical of obstructive jaundice.
Answer C AnswerC::C
Answer C Explanation AnswerCExp::This pattern is usually not seen.
Answer D AnswerD::D
Answer D Explanation AnswerDExp::This pattern is usually not seen.
Answer E AnswerE::E
Answer E Explanation AnswerEExp::This pattern is typical of hemolytic type jaundice.
Right Answer RightAnswer::B
Explanation [[Explanation::


The patient's presentation is typical for hemolytic anemia in the context of glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD is an enzyme catalyzing the rate limiting step of the pentose phosphate pathway. It transforms glucose-6-phosphate to 6-phosphogluconolactone while restoring NADPH needed to reduce glutathione. In patients with G6PD deficiency, NADPH cannot be restored in RBCs leading to glutathione depletion and susceptibility of RBCs to oxidative damage brought on by drugs and other substances notably fava beans (hence the name favism). Hemolysis in general leads to elevation in indirect unconjugated bilirubin which is not very water soluble. This fact is important since it explains the absence of bilirubin in the urine as water insoluble substances cannot be excreted by the kidneys. In parallel, conjugation of the excess indirect bilirubin occurs in the liver leading to increase excretion and a secondary increase in fecal stercobilin. Urine urobilinogen is an indicator of bile reabsortption, thus as bile excretion increases, urobilinogen increases as well.

Learning objective: Hemolytic jaundice is characterized by indirect (unconjugated) hyperbilirubinemia with absent urinary bilirubin and increase in urobilinogen.


References:

Beutler E. G6PD: population genetics and clinical manifestations. Blood Rev. 1996;10(1):45-52.

Le T, Bhushan V. First Aid for the USMLE Step 1 2014. McGraw-Hill Medical; 2014.
Educational Objective:
References: ]]

Approved Approved::No
Keyword WBRKeyword::Hemolytic jaundice, WBRKeyword::Bilirubin, WBRKeyword::unconjugated hyperbilirubinemia
Linked Question Linked::
Order in Linked Questions LinkedOrder::
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