On acclimatisation to high altitude (e.g., 4500 m), the initial respiratory alkalosis from hyperventilation is compensated by renal HCO₃⁻ excretion. However, the sustained increase in ventilation at altitude occurs because of an adaptation in peripheral chemoreceptors. What is this adaptation?

• A Resetting of carotid body chemoreceptors to a new lower PO₂ set-point, increasing hypoxic sensitivity; sustained high ventilation lowers PCO₂ but the respiratory drive remains elevated due to persistent hypoxaemia
• B Renal HCO₃⁻ wasting restores CSF PCO₂ to normal, removing central inhibition of ventilation and allowing hypoxic drive to predominate ✓
• C Central chemoreceptors at the ventral medulla increase HCO₃⁻ export into the CSF, restoring CSF pH and removing the braking effect on ventilation
• D Polycythaemia increases O₂ delivery sufficiently to abolish peripheral chemoreceptor discharge, allowing ventilation to normalise

Explanation

The initial hyperventilation at altitude causes respiratory alkalosis, which inhibits the central chemoreceptors (high CSF pH suppresses ventilatory drive). Over 2–5 days, the kidneys compensate by excreting HCO₃⁻ and reabsorbing Cl⁻ (renal compensation of respiratory alkalosis). As plasma [HCO₃⁻] falls and CSF pH normalises, the central chemoreceptor inhibition of ventilation is removed. The peripheral chemoreceptors continue to be driven by persistent hypoxaemia, and now without central alkalosis-mediated braking, ventilation increases further — this is 'ventilatory acclimatisation'. Additionally, carotid body sensitivity to hypoxia increases with acclimatisation.

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

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