Question Id: 10
A 25 year old woman returning from a 4 year stay in Africa presents with complaints of vomiting and diarrhea. On further examination, you notice that her breath smells like “garlic”. Biochemical studies reveal that she is deficient in a key compound of the Krebs cycle. A blood smear shows normal red blood cells. She denies any recent exposure to fire. Which of the following is the most likely cause of this patient's presentation?
Correct answer: C
This patient has been affected by arsenic poisoning. Arsenic is a water contaminant in many developing countries. It inhibits the Krebs cycle as follows: pyruvate dehydrogenase converts pyruvate to acetyl-CoA, which combines to oxaloacetate to form citrate. 5 cofactors are required for pyruvate dehydrogenase to function: pyrophosphate, FAD, NAD, CoA, lipoic acid. Arsenic allosterically inhibits enzymes that require lipoic acid. This causes accumulation of pyruvate, which leads to the gastrointestinal symptoms mentioned in the case (classically "rice water stools"). Severe toxicity cause neurological disturbances and death.
(A) is incorrect. Although lead can cause gastrointestinal problems, the lack of basophilic stippling of RBC makes it somewhat unlikely. Also, lead poisoning does not affect the Krebs cycle, and does not cause “garlic” breath.
(B) is incorrect. Although consumption of garlic can cause garlic smell in the breath, it is not known to gastrointestinal side effects. It does not affect enzymatic pathways, such as the Krebs cycle
(D) is incorrect. Carbon monoxide is most likely to occur as a result of exposure to fire, which is an absent feature in this case. Although CO poisoning has more widespread effects, it does not commonly affect the gastrointestinal system. It affects the cardiovascular system, causing tachycardia, hypertension, and sometimes myocardial ischemia. It also affects the central nervous system, leading to headache, dizziness and confusion. Other organs affected are the lungs, kidneys and muscles.
(E) is incorrect. Mercury poisoning typically causes sensory impairment (vision, hearing, and speech), disturbed sensation and a lack of coordination. Affected individuals commonly present with peripheral neuropathy (presenting as paresthesia or itching, burning or pain), skin discoloration (pink cheeks, fingertips and toes), edema (swelling), and desquamation (dead skin peels off in layers).
Arsenic interferes with cellular longevity by allosteric inhibition of an essential metabolic enzyme pyruvate dehydrogenate (PDH) complex, which catalyzes the oxidation of pyruvateto acetyl-CoA by NAD. With the enzyme inhibited, the energy system of the cell is disrupted resulting in a cellular apoptosis episode. Biochemically, arsenic prevents use of thiamine resulting in a clinical picture resembling thiamine deficiency. Poisoning with arsenic can raise lactate levels and lead to lactic acidosis. Low potassium levels in the cells increases the risk of experiencing a life-threatening heart rhythm problem from arsenic trioxide.
"Arsenic Poisoning". IHC World. Retrieved 2 May 2014