Acute high-altitude illness consists of a spectrum of clinical syndromes occurring in nonacclimatized individuals traveling to altitudes greater than 8,000 ft and ranges from a mild, almost flulike, systemic illness (acute mountain sickness or AMS) to life-threatening high-altitude pulmonary edema (HAPE), to highaltitude cerebral edema (HACE), to death. In general, the incidence and severity of illness increase with higher altitudes and rapid rates of ascent. All age groups may be affected, including otherwise healthy young persons and persons currently living in and adapted to high altitude who travel to a lower elevation and then reascend.

Acute high-altitude illness typically has an onset within 2 to 8 hours of ascent; this is important in our increasingly mobile society, in which a sea level resident may fly to a high-altitude destination within a few hours. Commercial airlines cruising at altitudes of 29,000 to 37,000 ft have cabin pressures equivalent of an altitude of approximately 6,000 to 8,000 ft (1,800-2,400 m) (FiO₂ of 15.2%-17.6%); thus, the airline passenger may be briefly exposed to conditions otherwise associated with the development of mild high-altitude illness.

Acute hypoxia is the syndrome resulting from severe and sudden exposure to extremely low levels of oxygen. This is typically seen during accidental decompression of commercial aircraft or associated with sudden failure of supplemental oxygen in individuals at very high altitudes. Less dramatic situations resulting in arterial desaturation include massive pulmonary embolus and flash pulmonary edema. Symptoms are related to the degree and time course of desaturation and include light-headedness, weakness, dizziness, changes in vision, and lethargy.

Although the ill effects resulting from rapid ascent to high altitudes have been known for years, much of the pathophysiology remains poorly understood. When a nonacclimatized person reaches a high altitude, the decreased ambient oxygen partial pressure results in immediate hypobaric hypoxemia; compensating for hypoxemia, the carotid artery and aortic body chemoreceptors and the brainstem induce an increased respiratory rate, resulting in hypocapnia and respiratory alkalosis. Unfortunately, alkalemia depresses the ventilatory drive, thus operating to increase hypoxemia further during this initial period of alkalosis, usually in the first 24 to 36 hours after ascent.