A 23-year-old healthy man who lives at sea level is attempting to trek to the Mount Everest base camp at an elevation of 5,334 m (17,500 ft). While hiking, he experiences mild shortness of breath, lightheadedness, headache, and fatigue. The patient reaches the base camp after 7 days, where he is evaluated at a high-altitude clinic. He appears exhausted, but physical examination is otherwise unrevealing. Which of the following physiologic changes has most likely occurred in this patient?
High-altitude illness | |
Pathogenesis |
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Physiologic responses |
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Complications |
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2,3-BPG = 2,3-bisphosphoglycerate; PiO2 = partial pressure of inspired oxygen. | |
This patient is most likely suffering from acute mountain sickness (AMS), a type of high-altitude illness resulting from low partial pressure of oxygen (pO2) in environments >2,500 m (8,000 ft). Although the fraction of oxygen in inspired air remains constant (21%) at different terrestrial elevations, barometric pressure drops with increasing altitude, leading to decreased pO2 in the air and lungs.
In an otherwise healthy patient, the pO2 rapidly equilibrates between the alveoli and arterial blood, causing hypoxemia when the pO2 drops below 80 mm Hg. Several acute physiological changes occur in response to the resulting hypobaric hypoxia:
Increased firing of peripheral chemoreceptors causes hyperventilation, which directly reduces hypoxemia and improves tissue oxygenation (Choice A).
Increased 2,3-bisphosphoglycerate (2,3-BPG) synthesis by erythrocytes, which shifts the O2-hemoglobin dissociation curve to the right, decreasing the affinity of hemoglobin for oxygen and facilitating the offloading of oxygen in peripheral tissues.
Hyperventilation also decreases the partial pressure of carbon dioxide, resulting in increased blood pH (respiratory alkalosis). Common symptoms of AMS include headache, fatigue, dyspnea, dizziness, and sleep disturbances. Most cases subside within 2 days but can progress to life-threatening cerebral and/or pulmonary edema in susceptible patients. In the absence of underlying pathology, symptoms typically resolve within 48 hours as the kidneys increase HCO3− excretion to compensate for the alkalosis, restoring pH toward the normal range and improving symptoms (Choice E).
(Choice B) Hypoxia induces widespread vasoconstriction of the pulmonary vasculature; this increases pulmonary vascular resistance and pulmonary arterial pressure and can result in pulmonary edema.
(Choice C) Hypoxemia stimulates increased erythropoietin production in the renal cortex, which results in polycythemia and increased oxygen-carrying capacity over time (days to weeks of sustained hypoxemia).
Educational objective:
People traveling to elevations >2500 m (8000 ft) can develop high-altitude illness, characterized by hypobaric hypoxia with the potential to develop life-threatening cerebral and/or pulmonary edema. Key adaptive responses to hypoxemia include hyperventilation to increase blood oxygenation and increased synthesis of 2,3-bisphosphoglycerate in erythrocytes (facilitating oxygen offloading into peripheral tissues).