Investigate the physiological side effects of valproic acid Results: You quickly

Question

Investigate the physiological side effects of valproic acid
Results:You quickly look up the side effects of valproic acid on your smart phone; it can cause nausea and vomiting, anorexia, carnitine deficiency, and abnormal bleeding, in patients on certain diets. You ask Jessie, and she says that she has experienced none of these—as far as she knows...

The investigation into the potential side effects of valproic acid has opened up seven new investigation options! Review your previous results so far in this case and consider whether this new information provides any logical explanation for Jessie’s odd metabolic limitations. What would you like to investigate next? The new options opened are:

Ask Jessie to think hard about whether she has been vomiting recently
Ask Jessie to think hard about whether she might have a carnitine deficiency Look for abnormal bleeding in the GI tract
Measure blood levels of carnitine
Measure blood levels of CoA
Measure blood levels of valproic acid
Send Jessie to a counselor to discuss the possibility that she might be anorexic

Ask Jessie to think hard about whether she has been vomiting recently
Result:Jessie restates that she has not had any bouts of nausea or vomiting recently. She is mildly annoyed by this question.

Ask Jessie to think hard about whether she might have a carnitine deficiency
Result:Jessie responds with a puzzled look and says: “Umm... I don’t think so...but what is carnitine anyway?” The physician you are shadowing steps in and clarifies that Jessie would not know whether she has a carnitine deficiency or not.

Look for abnormal bleeding in the GI tract
Result:You request that Jessie submit to an endoscopy and a colonoscopy. However, the physician you are shadowing disagrees with you - this is not a necessary set of procedures since Jessie does not report any bleeding and does not have any other apparent symptoms that would justify doing these procedures. She also notes that bleeding in the GI tract, even if it is found, does not explain the symptoms that Jessie is exhibiting.

Send Jessie to a counselor to discuss the possibility that she might be anorexic
Result:Jessie is deeply insulted by the insinuation; she has already stated that she eats a high calorie, but vegan, diet and takes your suggestion as an insinuation that she has been lying to you. She restates that she eats regularly and abundantly.

Measure blood levels of carnitine
Result:[Carnitine] = 5 mol/L (normal range: 24–64 mol/L)

Jessie has a severe carnitine deficiency! Carnitine is synthesized in humans from the amino acids methionine and lysine, but it is also acquired in the diet. As the name implies, carnitine is especially abundant in meat and dairy products. Because a typical omnivorous diet provides ~75% of a person’s carnitine, carnitine is sometimes considered a vitamin. However, since it can be synthesized de novo means that it is not a true vitamin. Valproic acid depletes carnitine stores in the body by multiple mechanisms but rarely results in true carnitine deficiency in

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most people. Something to consider: Why is Jessie experiencing carnitine deficiency? Is there any other aspect about her that might make her particularly sensitive to this side-effect of valproic acid?

Measure blood levels of CoA
Result:Levels of Coenzyme A are normal

Measure blood levels of valproic acid
Result:Valproic acid and its metabolites are detected in the blood. Levels are normal and appropriate for the dose that Jessie is taking to control her seizures

ENDING THE CASE AND THE ASSESSMENT QUESTIONS:

You have finished gathering information for this investigation, should be able to fully explain the reason(s) for Jesse’s incident in biochemical and physiological terms, and be able to fully justify and completely explain your reasoning based on the evidence gathered.

Interview patient to determine dietary habits and look for neurological problems Investigate past medical history
Measure blood levels of carnitine

If all of the criteria are not met, you are missing vital information to sufficiently explain this incident. You may be overlooking factors related to Jesse’s physiological state at the time of the accident or your investigation may not be detailed enough. Review your options and try to select options that would provide more information relevant to Jess’s condition. Try to think about what details you still cannot fully explain.

If you have reviewed your options and still need help, you may hire an outside consultant to review this case to provide guidance about what you might be missing. This person reviews your notes and gives you this helpful advice: In this case, it is important to consider the details that would cause abnormalities in Jesse’s physiological (metabolic) state at the time of the accident. You should completely examine her regular dietary habits, her past medical history, and her blood glucose and lipid levels. You should also make sure that you continue as in depth as possible in these lines of investigation.

Final Assessment Questions for “A Day at the Beach”:

19. Which of the following metabolic changes will occur in a typical human after a meal balanced in carbohydrates, protein, and fat is consumed? (Select ALL that apply!)

Liver glycogen synthesis increases.

Muscle glycogenolysis increases.

Liver gluconeogenesis decreases.

Insulin levels in the blood decrease.

Ketone body production in the liver is increased.

20. Which of the following metabolic changes will occur in a typical human during 12 hours of fasting? (Select ALL that apply.)

Liver glycogen synthesis decreases.

Liver glycogenolysis decreases.

Liver gluconeogenesis increases.

Liver fatty acid oxidation increases.

Ketone body formation increases.

21. Fatty acids in the bloodstream that are NOT part of TAGs or phospholipids: (Select ALL that apply!)

Are present at levels that are independent of epinephrine, glucagon, or insulin levels

Are carried by the protein albumin

Are soluble in the aqueous phase of the blood in free form

Are nonexistent; the blood only carries ketone bodies

Are carried as part of the lipid bilayer of LDLs and chylomicrons

Originate primarily from stored TAGs in adipose tissue

Originate primarily from dietary fats that have just been released into the bloodstream from intestinal cells

22. Which of the following statements about ketone bodies is/are true? (Select ALL that are true.)

One cause of ketone body formation can be that oxaloacetate is being used up by continuous gluconeogenesis during starvation, slowing the TCA cycle.

The production of ketone bodies frees up molecules of CoA so that -oxidation can continue.

Ketone bodies are produced only during vigorous exercise.

Ketone bodies provide an alternate substrate for glycolysis in the brain.

Ketone bodies are formed in the brain when -oxidation is interrupted.

23. Marasmus is the medical term for the condition that results from overall calorie starvation. In developed countries like the US, it is relatively uncommon. However, there is a common psychological illness, anorexia nervosa that results in the same symptoms and problems as marasmus. Both conditions result in high ratios of glucagon to insulin. Having a high ratio of glucagon to insulin would do which of the following in most healthy people? (Select ALL that apply!)

Promote mobilization of fatty acids from adipose tissue

Result in increased glycogen storage by the liver

Stimulate -oxidation by inhibiting the production of malonyl-CoA

Lead to increased concentrations of ketone bodies in the blood

24. What single problem in metabolism best explains Jessie's condition?

Jessie suffered from hypoglycemia due to anorexia.

Jessie was suffering from a deficiency of carnitine.

Jessie has a genetic disorder of CAT I or CAT II.

Jessie’s has a vitamin deficiency.

Jessie has a shortage of long-chain fatty acids.

Jessie has late-onset diabetes.

Explanation / Answer

Ans. 19 Liver glycogen synthesis would occur as there is a balanced diet of carbohydrates. The other metabolic changes wont occur as muscle gluconeogenesis occurs in fasting state or any physical activity, insulin production wont be reduced as the glucose supply is adequate, no ketone body production as the subject is not on fasting stage.

Ans 20. Ketone body formation would be increased due to 12 hour fasting a phenomenon commonly known as ketosis, Liver glycogenolysis would decrease and gluconeogenesis would increase within 12 hour of fasting. The other two would take some long time to occur and can be observed in 24 hour fasting.

Ans 22. In the given options about ketone bodies the statement that oxaloacetate has been used for ketone body formation thus slowing tca cycle would is appropriate. Ketone body providing an alternate substrate to brain during starvation apart from glycolysis is also true.

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