Toxicology: toxic effects and metabolism

6 ASCP MLS practice questions on Toxicology: toxic effects and metabolism, part of Chemistry. The first 6 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Hard

   A 45-year-old man is found confused. Results: pH 7.20, HCO3- 8 mmol/L, anion gap 30 mmol/L, osmolal gap 38 mOsm/kg, calcium 7.4 mg/dL [1.85 mmol/L], and many calcium oxalate crystals in the urine. Which substance did he most likely ingest?

   1. AIsopropanol
   2. BEthylene glycol
   3. CMethanol
   4. DEthanol

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   Answer: B · Ethylene glycol

   Alcohol dehydrogenase converts ethylene glycol to glycoaldehyde, then to glycolic acid, glyoxylic acid and oxalic acid. The unmetabolized glycol raises the osmolal gap, the acids (mainly glycolic acid) cause a high anion gap metabolic acidosis, and oxalate binds calcium, forming crystals in urine and kidney tissue and lowering serum calcium. Acute kidney injury is common. Treatment is fomepizole, often with hemodialysis.

   • A: Isopropanol raises the osmolal gap and acetone without causing acidosis.
   • C: Methanol causes acidosis and an osmolal gap with visual symptoms, but not oxalate crystals.
   • D: Ethanol raises the osmolal gap but does not cause oxalate crystals or this degree of acidosis.

2. Question 2 · Medium

   Serial salicylate levels after an overdose of enteric-coated aspirin are 25 mg/dL [1.8 mmol/L] at 2 hours and 48 mg/dL [3.5 mmol/L] at 6 hours. What best explains the rise?

   1. AOngoing absorption from the tablets
   2. BRelease of salicylate from tissue stores
   3. CSaturation of salicylate metabolism
   4. DHemoconcentration from vomiting

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   Answer: A · Ongoing absorption from the tablets

   Enteric-coated tablets dissolve slowly, and large doses can form a mass (bezoar) in the stomach, so absorption may continue for many hours. Peak levels can therefore come well after 6 hours, and a single early level can badly underestimate the overdose. Levels are repeated every 2 to 4 hours until they are clearly falling. Saturable metabolism slows elimination at high levels but cannot raise the level without further absorption.

   • B: Acidemia moves salicylate into tissues, not out of them.
   • C: Saturated metabolism slows the fall but does not make the level climb.
   • D: Vomiting cannot nearly double a drug level by concentrating the blood.

3. Question 3 · Hard

   An adult took a single acetaminophen overdose at 22:00. A level drawn at 06:00 the next day is 110 µg/mL [728 µmol/L]. The nomogram treatment line is 150 µg/mL [992 µmol/L] at 4 hours and halves every 4 hours. What is the correct interpretation?

   1. AAbove the line; give N-acetylcysteine
   2. BBelow the line; no antidote needed
   3. CAbove the line; give fomepizole
   4. DToo early; repeat at 12 hours

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   Answer: A · Above the line; give N-acetylcysteine

   The sample was drawn 8 hours after ingestion, and the treatment line falls from 150 µg/mL at 4 hours to 75 µg/mL [496 µmol/L] at 8 hours. The result of 110 µg/mL is well above the line, so N-acetylcysteine should be started; it works best within 8 to 10 hours of ingestion. Comparing the result with the 4-hour value of 150 µg/mL is the usual error. The nomogram applies only to a single acute ingestion with a known time, from 4 to 24 hours after it.

   • B: Comparing with the 4-hour value of 150 µg/mL instead of the 8-hour value of 75 µg/mL gives this error.
   • C: Fomepizole treats toxic alcohol poisoning, not acetaminophen overdose.
   • D: Any level from 4 hours onward can be plotted, so there is no need to wait.

4. Question 4 · Easy

   Methanol damages the optic nerve mainly through which metabolite?

   1. AOxalic acid
   2. BFormic acid
   3. CAcetaldehyde
   4. DAcetone

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   Answer: B · Formic acid

   Alcohol dehydrogenase converts methanol to formaldehyde, which aldehyde dehydrogenase converts to formic acid. Formate injures the optic nerve and retina and causes a high anion gap metabolic acidosis. Treatment blocks alcohol dehydrogenase with fomepizole (or ethanol) and removes the toxin by hemodialysis. Folinic acid or folate is also given to speed the breakdown of formate.

   • A: Oxalic acid comes from ethylene glycol and causes kidney injury and oxalate crystals.
   • C: Acetaldehyde comes from ethanol and causes flushing and nausea.
   • D: Acetone comes from isopropanol, which does not cause blindness.

5. Question 5 · Medium

   Two hours after a large aspirin overdose, an adult has pH 7.50, pCO2 28 mm Hg [3.7 kPa] and HCO3- 21 mmol/L. This pattern is best explained by:

   1. AAccumulation of lactic acid and ketoacids
   2. BDepression of the brainstem respiratory center
   3. CDirect stimulation of the respiratory center
   4. DLoss of stomach acid through repeated vomiting

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   Answer: C · Direct stimulation of the respiratory center

   Salicylate directly stimulates the respiratory center in the medulla, so hyperventilation and respiratory alkalosis appear first. These results fit acute respiratory alkalosis with only the small fall in bicarbonate expected from buffering. Later, uncoupling of oxidative phosphorylation and the build-up of lactic acid and ketoacids add a high anion gap metabolic acidosis, the typical mixed picture in adults. Young children often move quickly to metabolic acidosis.

   • A: Organic acids cause the later metabolic acidosis, which would lower bicarbonate much more.
   • B: Respiratory depression would raise pCO2, not lower it.
   • D: Vomiting causes metabolic alkalosis, with a raised bicarbonate.

6. Question 6 · Easy

   In acetaminophen overdose, liver cell necrosis is caused by:

   1. AUnchanged acetaminophen in the liver
   2. BGlucuronide conjugates of the drug
   3. CSulfate conjugates of the drug
   4. DNAPQI, once glutathione is used up

   Answer and explanation in LearnFree account