USMLE Step 1 Physiology Questions: Acid-Base Disorders – Vomiting, Aspirin Overdose and Diarrhea

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Acid-base questions appear on every USMLE Step 1 exam. Use the same steps every time: pH, then the primary disorder, then expected compensation, then the anion gap. Try these three questions, then open the explanations.

Question 1: Several days of vomiting

A 34-year-old woman has had repeated vomiting for 4 days due to a viral illness. She is lightheaded. Arterial blood gas shows pH 7.52, PaCO2 48 mm Hg and HCO3⁻ 38 mEq/L. Serum potassium is 2.9 mEq/L, and urine chloride is low. Which of the following best describes her acid-base status?

A. Respiratory acidosis with metabolic compensation
B. Metabolic alkalosis with appropriate respiratory compensation
C. Mixed metabolic alkalosis and respiratory alkalosis
D. Primary respiratory alkalosis
E. Metabolic acidosis with respiratory compensation

Correct answer: B. Metabolic alkalosis with appropriate respiratory compensation

The pH is high (alkalemia) and HCO3⁻ is high, so the primary disorder is metabolic alkalosis, caused by loss of gastric HCl. The expected PaCO2 is about 40 + 0.7 × (38 − 24) ≈ 50 mm Hg; the measured 48 is close, so the respiratory compensation is appropriate (hypoventilation). Volume depletion activates the renin-angiotensin-aldosterone system, which worsens hypokalemia and keeps the kidney reabsorbing bicarbonate. A low urine chloride indicates saline-responsive alkalosis, treated with IV normal saline and potassium.

Why the other options are wrong:

  • Respiratory acidosis would produce a low pH.
  • Mixed metabolic and respiratory alkalosis would show a low or normal PaCO2, not 48.
  • Primary respiratory alkalosis would show a low PaCO2.
  • Metabolic acidosis would show low pH and low HCO3⁻.

Question 2: Ringing in the ears after a large overdose

A 22-year-old woman is brought to the emergency department 3 hours after taking a large number of aspirin tablets. She has tinnitus, nausea and rapid breathing. Arterial blood gas shows pH 7.45, PaCO2 22 mm Hg and HCO3⁻ 15 mEq/L. Serum sodium is 140 mEq/L and chloride is 104 mEq/L. Which of the following best describes her acid-base status?

A. Pure metabolic acidosis with appropriate respiratory compensation
B. Pure respiratory alkalosis with renal compensation
C. Normal anion gap metabolic acidosis
D. Metabolic alkalosis
E. Mixed respiratory alkalosis and high anion gap metabolic acidosis

Correct answer: E. Mixed respiratory alkalosis and high anion gap metabolic acidosis

Salicylate toxicity classically causes a mixed disorder. Salicylates directly stimulate the respiratory center, causing respiratory alkalosis, and they also cause a high anion gap metabolic acidosis. Here the anion gap is 140 − (104 + 15) = 21 (high). For a HCO3⁻ of 15, Winter’s formula predicts PaCO2 = 1.5 × 15 + 8 = 30.5 ± 2. The measured PaCO2 of 22 is much lower, so there is an additional primary respiratory alkalosis. That is why the pH is near normal. Treatment includes activated charcoal (early), urine alkalinization with sodium bicarbonate, and hemodialysis in severe cases.

Why the other options are wrong:

  • Pure metabolic acidosis would have a PaCO2 near 30, not 22.
  • Renal compensation takes days; this overdose was 3 hours ago, and the anion gap is high.
  • Normal anion gap is incorrect; the gap here is 21.
  • Metabolic alkalosis would show a high HCO3⁻.

Question 3: Profuse watery diarrhea and a low bicarbonate

A 40-year-old man has had profuse watery diarrhea for 5 days. Laboratory studies show serum sodium 136 mEq/L, chloride 114 mEq/L, HCO3⁻ 14 mEq/L and potassium 3.0 mEq/L. Arterial pH is 7.29 and PaCO2 is 29 mm Hg. Which of the following is the most likely cause of this acid-base pattern?

A. Diabetic ketoacidosis
B. Lactic acidosis
C. Loss of bicarbonate in the stool
D. Methanol ingestion
E. Prolonged vomiting

Correct answer: C. Loss of bicarbonate in the stool

The low pH and low HCO3⁻ indicate metabolic acidosis. The anion gap is 136 − (114 + 14) = 8, which is normal, and chloride is high: a normal anion gap (hyperchloremic) metabolic acidosis. The most common cause is diarrhea, with loss of bicarbonate-rich intestinal fluid. Winter’s formula predicts PaCO2 = 1.5 × 14 + 8 = 29 ± 2, so respiratory compensation is appropriate. Other causes of normal anion gap acidosis include renal tubular acidosis, acetazolamide and saline infusion.

Why the other options are wrong:

  • DKA causes a high anion gap metabolic acidosis.
  • Lactic acidosis causes a high anion gap.
  • Methanol causes a high anion gap and a high osmolal gap.
  • Vomiting causes metabolic alkalosis.

Key takeaways

  • Vomiting: hypochloremic, hypokalemic metabolic alkalosis; low urine chloride means saline-responsive.
  • Salicylate toxicity: mixed respiratory alkalosis and high anion gap metabolic acidosis.
  • Diarrhea: normal anion gap (hyperchloremic) metabolic acidosis; use Winter’s formula to check compensation.

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Written and reviewed by Dr. Ray Makar, MD, dermatologist with 20 years of clinical practice. Last reviewed: October 2026. For exam preparation only, not medical advice.

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