A mountaineer ascends from sea level (PO₂ 160 mmHg) to 5000 m altitude (barometric pressure 405 mmHg, PO₂ ≈ 85 mmHg) over 2 weeks. Which compensatory adaptations occur in sequence to maintain oxygen delivery?
- A Immediate: bradycardia and increased stroke volume to maximize cardiac output. Days 1–3: peripheral vasoconstriction. Days 3–14: polycythemia
- B Immediate: metabolic acidosis triggers Kussmaul breathing. Days 1–3: EPO release. Days 3–14: left-shift of ODC to maximize pulmonary O₂ loading
- C Immediate: hyperventilation (↑VE, ↓PaCO₂, respiratory alkalosis). Days 1–3: renal HCO₃⁻ excretion compensates alkalosis. Days 3–14: EPO-driven erythropoiesis raises hemoglobin mass and 2,3-DPG rises, right-shifting ODC to improve O₂ unloading ✓
- D Immediate: increased 2,3-DPG production. Days 1–3: tachycardia. Days 3–14: renal HCO₃⁻ retention to counteract respiratory alkalosis
Correct answer: C. Immediate: hyperventilation (↑VE, ↓PaCO₂, respiratory alkalosis). Days 1–3: renal HCO₃⁻ excretion compensates alkalosis. Days 3–14: EPO-driven erythropoiesis raises hemoglobin mass and 2,3-DPG rises, right-shifting ODC to improve O₂ unloading
Explanation
Acute altitude exposure causes hypoxic hyperventilation (peripheral chemoreceptor response), lowering PaCO₂ and raising pH (respiratory alkalosis)—this blunts the ventilatory drive. Over 1–3 days, the kidneys excrete HCO₃⁻, compensating the alkalosis and restoring chemoreceptor sensitivity, allowing further ventilatory acclimatization. Sustained hypoxia stimulates HIF-1α-mediated renal EPO production, driving erythropoiesis over days to weeks, while 2,3-DPG rises to right-shift the ODC, facilitating tissue O₂ unloading at lower PO₂.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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