At high altitude (4500 m), a climber's alveolar PO2 has dropped and she develops mountain sickness. Her arterial pH is 7.49, PaCO2 is 28 mmHg, and HCO3⁻ is 21 mEq/L. Which sequence of physiological events BEST describes the acclimatization that has occurred?

• A Hypoxia → peripheral chemoreceptor stimulation → hyperventilation → respiratory alkalosis → renal bicarbonate excretion over days restoring pH toward normal (renal acclimatization) ✓
• B Hypoxia → central chemoreceptor stimulation → hyperventilation → respiratory acidosis corrected by metabolic alkalosis
• C Hypoxia → carotid body hypertrophy → sustained tachycardia → increased O2 delivery compensating for altitude without ventilatory changes
• D Hypoxia → EPO release → polycythemia → increased O2 carrying capacity as the PRIMARY acute acclimatization response

Explanation

Altitude acclimatization begins with hypoxia stimulating peripheral chemoreceptors (carotid bodies) to increase ventilation. Hyperventilation reduces PaCO2, causing respiratory alkalosis. Over 24–72 hours, the kidneys respond by excreting bicarbonate (via carbonic anhydrase-dependent mechanisms, reduced HCO3⁻ reabsorption in the proximal tubule), lowering serum HCO3⁻ from 24 toward 18–21 mEq/L, partially restoring pH. This is renal acclimatization and is the reason acetazolamide (a carbonic anhydrase inhibitor forcing bicarbonate wasting) is used for altitude sickness prophylaxis. The patient's values (pH 7.49, PaCO2 28, HCO3⁻ 21) confirm partial renal compensation of the respiratory alkalosis. Central chemoreceptors (option B) primarily sense PaCO2/pH and are actually inhibited by the initial alkalosis, partially blunting hyperventilation. Polycythemia (option D) takes days to weeks and is not the primary acute response.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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