At an altitude of 5000m (PO2 ~75 mmHg), a mountaineer after 2 weeks shows which pattern of ventilatory acclimatization and its mediators?

• A Sustained hyperventilation driven by peripheral chemoreceptors (hypoxia-sensitive); initial respiratory alkalosis partially compensated by renal bicarbonate excretion (normalization of CSF pH allowing central chemoreceptors to sustain the drive); erythropoiesis via EPO increasing Hb ✓
• B Reduced ventilation due to acclimatization reducing chemoreceptor sensitivity to hypoxia
• C Hyperventilation only during sleep; wakefulness ventilation normalizes via central adaptation
• D Increased ventilation initially, then return to baseline as peripheral chemoreceptors desensitize to hypoxia over 2 weeks

Explanation

Altitude acclimatization involves a staged ventilatory response: (1) Immediate: peripheral carotid body chemoreceptors sense hypoxia → hyperventilation → respiratory alkalosis (PaCO2 falls, pH rises). (2) Initially, alkalosis reduces ventilatory drive at central chemoreceptors and limits hyperventilation. (3) Over 2–7 days: kidneys excrete HCO3- (renal compensation for respiratory alkalosis), normalizing CSF and blood pH. With alkalosis corrected, central chemoreceptors are no longer inhibited by alkalinity, allowing sustained peripheral hypoxic drive to maintain hyperventilation. Erythropoietin (EPO, stimulated by HIF-1 in renal peritubular cells via hypoxia) increases RBC production over 1–3 weeks, raising Hb and oxygen-carrying capacity. Peripheral chemoreceptors do not desensitize to hypoxia; instead, their sensitivity may increase with altitude exposure.

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

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