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[Dr. Shapiro] This is Dr. Samantha Shapiro, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest trusted content from the best minds in medicine. And now, onto the episode.
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[Dr. Handy] Hi, everyone. Welcome back to Harrison's Podclass. We're your co-hosts. I'm Dr. Cathy Handy.
[Dr. Wiener] And I'm Dr. Charlie Wiener, and we're joining you from the Johns Hopkins School of Medicine.
[Dr. Handy] Welcome to episode 105, a 24-year-old man with altered mental status.
[Dr. Wiener] Okay, Cathy, today you are seeing a 24-year-old man who has type one diabetes and he's brought to the emergency department from his workplace by the emergency medical systems because of altered mental status. His spouse shows up soon thereafter and she says that he has been very depressed recently about having diabetes and he's actually expressed suicidal thoughts. He works as an auto mechanic, and his only medication is insulin. His spouse does not know if he took his morning dose of insulin before he left for work. He does not use alcohol, cigarettes, or illicit drugs. On exam, he's somnolent with normal vital signs and no focal neurologic findings. His initial laboratory studies are notable for a sodium of 130, potassium of 4, chloride of 90, bicarbonate of 15, BUN of 24, creatinine of 1, and a glucose of 90.
[Dr. Handy] Okay, so initially I was thinking that there was going to be a really abnormal glucose level, but with a normal glucose I'd be less concerned about hypoglycemia causing his symptoms, or diabetic ketoacidosis with really high glucoses as a primary cause of his symptoms. Are there any additional tests that have been sent?
[Dr. Wiener] Yeah, so you're getting some studies back even as we speak, and additional studies show that he has a negative toxicology screen for alcohol, narcotics, or other drugs. His liver function tests are stone-cold normal, his serum ketones are negative, his serum alcohol is not detectable, and his lactate is normal.
[Dr. Handy] All right, so just to summarize about what we know now, his only real symptom is depressed sensorium with no neurologic focality. However, the clue is in his labs that show a notable anion gap metabolic acidosis, and we've already said that that's not explained by ketones or lactate, which would be some of the more common reasons. Any other data?
[Dr. Wiener] Yeah, just go back to that. So you calculated his anion gap at 25, right? And that's elevated?
[Dr. Handy] Correct.
[Dr. Wiener] Okay. Well, his serum osmolality comes back at 310 and arterial blood gas on room air reveals a pH of 7.28, a PCO2 of 20, and a PO2 of 110. The question's going to ask, which of the following has he most likely ingested? And the options are A. acetaminophen; B. cocaine; C. cyanide; D. ethylene glycol; or E. sulfonylurea.
[Dr. Handy] All right, just to add to the summary before, he has an elevated osmolar gap and an elevated osmolal gap.
[Dr. Wiener] Okay, we already know that his anion gap is 25, you told us that, but before we go further, remind us about the osmolal gap.
[Dr. Handy] Yep, so the anion gap is elevated. To calculate the osmolal gap, first, we can use the equation two times the serum sodium plus glucose over 18, plus the blood urea nitrogen, divided by 2.8. So that's how we calculate the estimated serum osmolality and multiplying the sodium by two takes into account the chloride and bicarbonate anions that bind to sodium.
[Dr. Wiener] Okay, so for this patient, when you use that equation, you got 273, and his measured osmolality in the lab is 310. So that gives us an osmolal gap of 37, right?
[Dr. Handy] Yes, and the upper allowable limit of what we would consider normal is 10. So with a value of 37, he would be way up there.
[Dr. Wiener] Okay, so what do you conclude from that?
[Dr. Handy] The anion gap acidosis with no evidence of ketones or lactate tells you that there's an additional solute that's unmeasured in this patient's serum and is likely causing his clinical and laboratory abnormalities.
[Dr. Wiener] What are the most common causes of an anion gap metabolic acidosis with an elevated osmolal gap?
[Dr. Handy] The most common cause is alcohol intoxication, but we know that that's not the cause here because his level was undetectable. Of the choices listed, I would say that the answer is D., that he ingested ethylene glycol. So ingestion of either ethylene glycol or methanol will present with this clinical toxidrome as well.
[Dr. Wiener] Ethylene glycol is antifreeze, right?
[Dr. Handy] Yeah, and I suspect that he may have had access to it in his workplace. And you can also see this toxidrome when patients ingest it in lieu of alcohol.
[Dr. Wiener] How does ethylene glycol poisoning present beyond mental status changes and how would you treat this man?
[Dr. Handy] So it can also cause nausea and vomiting, calcium oxalate crystal urea, renal failure, coma, seizures, hypotension, and even ARDS in severe cases. Treatment consists of sodium bicarbonate to correct the acidemia, diamine, folinic acid, magnesium, and a high-dose paradoxine to facilitate metabolism. In severe cases, you can administer fomepizole, which is a competitive inhibitor of alcohol dehydrogenase and blocks metabolism into toxic intermediates. Finally, hemodialysis may be tried for persistent acidosis or lack of clinical improvement or in renal dysfunction.
[Dr. Wiener] Okay, and let's just briefly run through the other options and highlight why those were incorrect in this patient.
[Dr. Handy] Yeah, so acetaminophen overdose may cause acute liver injury and even fulminant liver failure in the hours or days after a toxic ingestion. We heard that there was no evidence of any abnormalities in his liver function tests, so that wouldn't apply. Cocaine intoxication may cause central and peripheral sympathetic stimulation. Cyanide inhibits mitochondrial electron transport and oxidative metabolism, so the patient physiologically has signs and symptoms of profound hypoxia with apparently normal oxygen levels. It's similar to carbon monoxide poisoning. And then lastly, sulfonylurea overdose will present with hypoglycemia.
[Dr. Wiener] Great, so the teaching point in today's case is that the osmolal gap may be helpful to determine the cause of an unexplained high anion gap metabolic acidosis. Remember, the most common causes of high anion gap metabolic acidosis are either the presence of lactate or ketones. So if they're not present, you have to look for other sources. Elevation of the osmolal gap is characteristic of intoxication or poisoning with ethylene glycol or methanol or alcohol.
[Dr. Handy] And you can read more about this in the chapter on poisoning and drug overdose.
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