Physiology for USMLE Step 1

A healthy volunteer is given a drug that selectively blocks the Na⁺/K⁺/2Cl⁻ cotransporter in the thick ascending limb of the loop of Henle. Which set of changes would you expect?

1. Metabolic acidosis with a normal anion gap That follows carbonic anhydrase inhibition with acetazolamide. Loop diuretics cause a contraction ALKALOSIS instead.
2. Increased urinary calcium excretion and reduced ability to concentrate urine correct Correct. The cotransporter generates the lumen-positive potential that drives paracellular calcium and magnesium reabsorption, so blocking it produces calciuria and magnesuria. It also dissipates the medullary concentration gradient, so urine cannot be maximally concentrated.
3. Hyperkalemia from reduced distal sodium delivery The opposite. Increased distal sodium delivery drives potassium secretion, so loop diuretics cause hypokalemia.
4. Increased medullary interstitial osmolality The opposite. The cotransporter is what builds the medullary gradient, so blocking it lowers medullary osmolality.
5. Decreased urinary calcium excretion and hypercalcemia That is the THIAZIDE effect, acting on the distal convoluted tubule, which is why thiazides are used in recurrent calcium stone formers and loop diuretics are not.

The point: Loops lose calcium; thiazides keep it. Loops are therefore used in hypercalcemia (with fluids) and thiazides in calcium stone prevention. Both cause hypokalemic metabolic alkalosis. Loops also cause ototoxicity, particularly with aminoglycosides.

Source: USMLE Content Outline — renal physiology and pharmacology NBME / FSMB (USMLE programme) · tier 0, exam blueprint / regulator

A patient is given a pure alpha-1 agonist. Mean arterial pressure rises from 85 to 115 mm Hg and heart rate falls from 78 to 58 beats per minute. The patient is not taking any other drug. What mediates the fall in heart rate?

1. Beta-2 mediated vasodilation in skeletal muscle A pure alpha-1 agonist does not act at beta-2, and vasodilation would lower rather than raise the pressure.
2. Increased circulating atrial natriuretic peptide ANP does rise with atrial stretch, but it acts over minutes to hours on volume, not on the beat-to-beat heart rate seen here.
3. Baroreceptor-mediated increase in vagal tone correct Correct. Carotid sinus and aortic arch stretch receptors fire more when pressure rises, increasing parasympathetic outflow to the SA node and withdrawing sympathetic tone. This reflex bradycardia is the giveaway for a pure vasoconstrictor.
4. Reduced preload from venodilation Alpha-1 stimulation causes venoCONSTRICTION, which increases preload.
5. Direct alpha-1 blockade of the SA node The drug is an agonist, and the SA node is governed by beta-1 rather than alpha-1 receptors.

The point: Reflex bradycardia with a rise in pressure means a pure alpha agonist (phenylephrine). Reflex TACHYcardia with a fall in pressure means a vasodilator. If a pressor raises pressure without reflex bradycardia, suspect concurrent beta-1 activity.

Source: USMLE Content Outline — cardiovascular physiology NBME / FSMB (USMLE programme) · tier 0, exam blueprint / regulator

A healthy 24-year-old is studied upright at rest. Compared with the apex of the lung, the base has higher ventilation and higher perfusion, but a LOWER ventilation/perfusion ratio. Which set of alveolar gas values best describes the apex relative to the base?

1. Higher PO2 and lower PCO2 at the apex correct Correct. Gravity reduces perfusion at the apex more than it reduces ventilation, so the apical V/Q is high, closer to dead space. Alveolar gas there approaches inspired air: high PO2, low PCO2. This is also why reactivated tuberculosis favours the apex.
2. Higher PO2 and higher PCO2 at the apex Physiologically incoherent: a high V/Q region washes out CO2 as it takes up O2, so the two move in opposite directions.
3. Lower PO2 and higher PCO2 at the apex That is the base, where the low V/Q makes alveolar gas approach mixed venous blood.
4. Identical PO2 and PCO2 throughout the upright lung Only true in zero gravity or in the supine subject along the vertical axis; upright, the gradient is substantial.
5. Lower PO2 and lower PCO2 at the apex This is the pattern of a shunt, not of a high V/Q region.

The point: Apex: high V/Q, high PO2, low PCO2, favours TB and centriacinar emphysema is not apical, but panacinar from alpha-1 antitrypsin deficiency is BASAL. Base: low V/Q, more ventilation and much more perfusion in absolute terms.

Source: USMLE Content Outline — respiratory physiology NBME / FSMB (USMLE programme) · tier 0, exam blueprint / regulator