Physiology for the USMLE: Exam Questions and Preparation

Physiology on the USMLE is about how normal systems respond when something changes. Questions ask what happens to a variable, in what direction and why, and often include a graph, a pressure-volume loop or a laboratory table.

Step 1 is reported as pass/fail, and its questions are integrated across disciplines and organ systems, so the subject labels below are study aids, not separate exams. The practice questions here are original and written to show the style of reasoning the exam rewards; they are not real exam items. Confirm the current content outline on the official USMLE website.

How Physiology is tested

Expect cardiovascular, respiratory, renal and acid-base questions to dominate, followed by endocrine, GI, neuro and muscle physiology. Many items are predict-the-change problems, where you apply a principle to a new scenario.

High-yield topics

Cardiac output, the Frank-Starling relationship and pressure-volume loops
Pulmonary mechanics, ventilation-perfusion relationships and the oxygen-hemoglobin curve
Renal clearance, glomerular filtration, tubular transport and acid-base disorders
Endocrine feedback loops and hormone actions
GI hormones, secretion and absorption
Membrane potentials, action potentials and muscle contraction

Preparation approach

Learn each system as a set of relationships, then practice changing one variable and predicting the others.
Draw the key graphs from memory, such as the pressure-volume loop and the oxygen-hemoglobin curve, and shift them for each scenario.
Do acid-base problems with a fixed routine: check the pH, find the primary disorder, then check compensation and the anion gap.
Use practice questions to build speed at reading tables and graphs.

Practice questions

Question 1

A patient has pH 7.25, PaCO2 25 mm Hg and bicarbonate 11 mEq/L. Which disorder best explains these values?

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

Answer: C. A low pH with a low bicarbonate is metabolic acidosis. The expected PaCO2 by Winter's formula is about 1.5 x 11 + 8 = 24.5, so the respiratory compensation is appropriate.

Question 2

Which change shifts the oxygen-hemoglobin dissociation curve to the right?

A. Decreased temperature
B. Decreased 2,3-bisphosphoglycerate
C. Decreased PCO2
D. Increased 2,3-bisphosphoglycerate
E. Increased pH

Answer: D. A right shift reduces hemoglobin's affinity for oxygen, and it is caused by raised 2,3-BPG, temperature, PCO2 and H+ (lower pH), which favors oxygen release to tissues.

Question 3

A substance is freely filtered and is neither reabsorbed nor secreted. Its urine concentration is 12 mg/mL, urine flow is 1 mL/min and plasma concentration is 0.1 mg/mL. What is the glomerular filtration rate?

A. 12 mL/min
B. 60 mL/min
C. 120 mL/min
D. 240 mL/min
E. 1,200 mL/min

Answer: C. For such a substance, clearance equals GFR: (12 mg/mL x 1 mL/min) / 0.1 mg/mL = 120 mL/min.

Make it a plan

Put these subjects inside a dedicated study block with timed question blocks and careful review. See our Step 1 preparation timeline for a schedule and weekly milestones. This article is general educational guidance and not an individualized study plan.

Educational content only. Confirm current exam requirements with USMLE.