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{{WBRQuestion
{{WBRQuestion
|QuestionAuthor={{Rim}}
|QuestionAuthor={{Rim}} (Reviewed by {{YD}})
|ExamType=USMLE Step 1
|ExamType=USMLE Step 1
|MainCategory=Biochemistry
|MainCategory=Biochemistry
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|MainCategory=Biochemistry
|MainCategory=Biochemistry
|SubCategory=General Principles
|SubCategory=General Principles
|MainCategory=Biochemistry
|MainCategory=Biochemistry
|MainCategory=Biochemistry
|MainCategory=Biochemistry
|MainCategory=Biochemistry
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|MainCategory=Biochemistry
|MainCategory=Biochemistry
|SubCategory=General Principles
|SubCategory=General Principles
|Prompt=A 45-year-old man with previous history of hepatitis C infection complains of progressively increasing fatigue, loss of appetite and bleeding tendency. Physical exam reveals yellowing of the sclera and the skin in addition to an increase in the abdominal girth. During physical exam, the patient is asked to push his hands down on the midline of the abdomen, the examiner then taps one flank, while feeling on the other flank for the tap.  The examiner is able to feel the tap on the other side. A set of laboratory tests is ordered. What are the expected changes in the BUN and ammonia blood levels respectively?
|Prompt=A 59-year-old man, with a history of chronic hepatitis C infection, presents to the physician's office with complaints of progressively worsening fatigue, loss of appetite, and bleeding tendency. Physical examination is remarkable for jaundiced skin, increase in abdominal girth, gynecomastia, and palmar erythema. The patient is asked to push his hands down on the midline of the abdomen while the examiner taps one flank, and the tap is then felt on the other flank. A set of laboratory tests is ordered. Which set of BUN and ammonia changes is associated with the patient's condition?<br>
|Explanation=The patient complains of [[fatigue]], loss of appetite and bleeding tendency in the context of [[hepatitis C]] infection. Moreover, the exam reveals [[jaundice]] and [[ascites]] as demonstrated by the fluid wave test. The fluid wave test s performed by having the patient push their hands down on the midline of the abdomen, then the examiner taps one flank, while feeling on the other flank for the tap. Fluid allows the tap to be felt on the other side. The patient's signs and symptoms are most likely due to liver cirrhosis secondary to chronic hepatitis C.
 
[[Ammonia]] is converted in the liver to urea by a set of mitochondrial and cytoplasmic enzymes in the hepatocytes.  In [[cirrhosis]], [[hepatocyte]]s are affected; therefore, urea cycle is not as functional as it is in a normal liver. Ammonia is not converted to urea leading to an elevated blood level of ammonia and a decreased level of blood urea nitrogen (BUN) level.
[[Image:WBR0970table.jpg|700px]]
|Explanation=Hepatic cirrhosis should be suspected among patients with chronic hepatitis infection who present with worsening [[fatigue]], loss of appetite, and bleeding tendency (acquired coagulopathy due to reduced synthesis of coagulation factors in the liver). In this vignette, the findings on physical examination (jaundiced skin, ascites, gynecomastia, and palmar erythema) further raise the suspicion of hepatic cirrhosis. Ascites is evaluated using the fluid wave test, whereby the patient is asked to push his hands down on the midline of the abdomen while the examiner taps one flank and feels the tap at the other flank.


'''Educational objective:'''
High concentration of ammonia is toxic, and the blood concentration of ammonia is normally maintained very low. Urea is synthesized from ammonia within the periportal hepatocytes, and ammonia is further transformed into glutamine within the perivenous hepatocytes. Both processes help in the elimination of ammonia build-up in a normal liver. In [[cirrhosis]], increased hepatocyte loss and extrahepatic portosystemic shunts result in hyperammonemia caused by reduced hepatic urea synthesis. Ammonia is not converted to urea, resulting in an elevated concentration of ammonia and a reduced concentration of urea (and blood urea nitrogen).
[[Ammonia]] is converted in the liver to urea by a set of [[mitochondria|mitochondrial]] and cytoplasmic enzymes in the hepatocytes. In [[cirrhosis]], the urea cycle is affected leading to an elevated blood level of ammonia and a decreased level of blood urea level.
|AnswerA=A
|AnswerA=Decreased, decreased
|AnswerAExp=In [[cirrhosis]], serum [[ammonia]] concentration is elevated and blood [[urea]] nitrogen concentration is reduced.
|AnswerAExp=This answer is incorrect because in [[cirrhosis]] the blood level of [[ammonia]] is elevated the blood [[urea]] nitrogen (BUN) level is decreased.
|AnswerB=B
|AnswerB=Decreased, increased
|AnswerBExp=In [[cirrhosis]], serum [[ammonia]] concentration is elevated and blood [[urea]] nitrogen concentration is reduced.
|AnswerBExp=In [[cirrhosis]], [[hepatocyte]]s are affected; therefore, urea cycle is not as functional as it is in a normal liver. Ammonia is not converted to urea leading to an elevated blood level of [[ammonia]] and a decreased level of blood [[urea]] nitrogen (BUN) level.
|AnswerC=C
|AnswerC=Increased, unchanged
|AnswerCExp=In [[cirrhosis]], serum [[ammonia]] concentration is elevated and blood [[urea]] nitrogen concentration is reduced.
|AnswerCExp=This answer is incorrect because in [[cirrhosis]] the blood level of [[ammonia]] is elevated the blood [[urea]] nitrogen (BUN) level is decreased.
|AnswerD=D
|AnswerD=Increased, increased
|AnswerDExp=In [[cirrhosis]], increased hepatocyte loss and extrahepatic portosystemic shunts result in hyperammonemia caused by reduced hepatic urea synthesis. Ammonia is not converted to urea, resulting in an elevated concentration of ammonia and a reduced concentration of urea (and blood urea nitrogen).
|AnswerDExp=This answer is incorrect because in [[cirrhosis]] the blood level of [[ammonia]] is elevated the blood [[urea]] nitrogen (BUN) level is decreased.
|AnswerE=E
|AnswerE=Unchanged, increased
|AnswerEExp=In [[cirrhosis]], serum [[ammonia]] concentration is elevated and blood [[urea]] nitrogen concentration is reduced.
|AnswerEExp=This answer is incorrect because in [[cirrhosis]] the blood level of [[ammonia]] is elevated the blood [[urea]] nitrogen (BUN) level is decreased.
|EducationalObjectives=In [[cirrhosis]], increased hepatocyte loss and extrahepatic portosystemic shunts result in hyperammonemia caused by reduced hepatic urea synthesis. Ammonia is not converted to urea, resulting in an elevated concentration of ammonia and a reduced concentration of urea (and blood urea nitrogen).
|RightAnswer=B
|References=Lockwood AH, McDonald JM, Reiman RE, et al. The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia. J Clin Invest. 1979;63(3):449-60.<br>
|WBRKeyword=Urea, ammonia, Cirrhosis,
First Aid 2014 page 109, 361
|Approved=No
|RightAnswer=D
|WBRKeyword=Urea, Ammonia, Cirrhosis, Fluid wave test, Urea cycle, Urea synthesis, Blood urea nitrogen, BUN, Hyperammonemia
|Approved=Yes
}}
}}

Revision as of 13:30, 10 March 2015

 
Author [[PageAuthor::Rim Halaby, M.D. [1] (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Biochemistry
Sub Category SubCategory::General Principles
Prompt [[Prompt::A 59-year-old man, with a history of chronic hepatitis C infection, presents to the physician's office with complaints of progressively worsening fatigue, loss of appetite, and bleeding tendency. Physical examination is remarkable for jaundiced skin, increase in abdominal girth, gynecomastia, and palmar erythema. The patient is asked to push his hands down on the midline of the abdomen while the examiner taps one flank, and the tap is then felt on the other flank. A set of laboratory tests is ordered. Which set of BUN and ammonia changes is associated with the patient's condition?

]]

Answer A AnswerA::A
Answer A Explanation [[AnswerAExp::In cirrhosis, serum ammonia concentration is elevated and blood urea nitrogen concentration is reduced.]]
Answer B AnswerB::B
Answer B Explanation [[AnswerBExp::In cirrhosis, serum ammonia concentration is elevated and blood urea nitrogen concentration is reduced.]]
Answer C AnswerC::C
Answer C Explanation [[AnswerCExp::In cirrhosis, serum ammonia concentration is elevated and blood urea nitrogen concentration is reduced.]]
Answer D AnswerD::D
Answer D Explanation [[AnswerDExp::In cirrhosis, increased hepatocyte loss and extrahepatic portosystemic shunts result in hyperammonemia caused by reduced hepatic urea synthesis. Ammonia is not converted to urea, resulting in an elevated concentration of ammonia and a reduced concentration of urea (and blood urea nitrogen).]]
Answer E AnswerE::E
Answer E Explanation [[AnswerEExp::In cirrhosis, serum ammonia concentration is elevated and blood urea nitrogen concentration is reduced.]]
Right Answer RightAnswer::D
Explanation [[Explanation::Hepatic cirrhosis should be suspected among patients with chronic hepatitis infection who present with worsening fatigue, loss of appetite, and bleeding tendency (acquired coagulopathy due to reduced synthesis of coagulation factors in the liver). In this vignette, the findings on physical examination (jaundiced skin, ascites, gynecomastia, and palmar erythema) further raise the suspicion of hepatic cirrhosis. Ascites is evaluated using the fluid wave test, whereby the patient is asked to push his hands down on the midline of the abdomen while the examiner taps one flank and feels the tap at the other flank.

High concentration of ammonia is toxic, and the blood concentration of ammonia is normally maintained very low. Urea is synthesized from ammonia within the periportal hepatocytes, and ammonia is further transformed into glutamine within the perivenous hepatocytes. Both processes help in the elimination of ammonia build-up in a normal liver. In cirrhosis, increased hepatocyte loss and extrahepatic portosystemic shunts result in hyperammonemia caused by reduced hepatic urea synthesis. Ammonia is not converted to urea, resulting in an elevated concentration of ammonia and a reduced concentration of urea (and blood urea nitrogen).
Educational Objective: In cirrhosis, increased hepatocyte loss and extrahepatic portosystemic shunts result in hyperammonemia caused by reduced hepatic urea synthesis. Ammonia is not converted to urea, resulting in an elevated concentration of ammonia and a reduced concentration of urea (and blood urea nitrogen).
References: Lockwood AH, McDonald JM, Reiman RE, et al. The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia. J Clin Invest. 1979;63(3):449-60.
First Aid 2014 page 109, 361]]

Approved Approved::Yes
Keyword WBRKeyword::Urea, WBRKeyword::Ammonia, WBRKeyword::Cirrhosis, WBRKeyword::Fluid wave test, WBRKeyword::Urea cycle, WBRKeyword::Urea synthesis, WBRKeyword::Blood urea nitrogen, WBRKeyword::BUN, WBRKeyword::Hyperammonemia
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