Acute mountain sickness: the "poison of the pass"

Abstract

Few sights are more breathtaking and inspirational than a mountain peak. Yet, behind the innocence and majesty of one of nature's wonders lies a sleeping evil, acute mountain sickness (AMS). The constellation of symptoms that characterizes AMS is a frequent cause of morbidity and occasionally mortality and affects 25% of travelers sojourning to altitudes between 1900 and 3000 m (about 6,200-9,850 ft).1 Joseph de Acosta, a Jesuit priest, presented the first classical account of the physical symptoms associated with mountain sickness in 1604 during a climbing expedition to Peru2: I was suddenly surprised with so mortal and strange a pang, that I was ready to fall from the top to the ground....I was surprised with such pangs of straining and casting as I thought to cast up my heart too: for having cast up meate, fleugme and choller both yellow and greene, in the end I cast up blood with the straining of my stomach. To conclude, if this had continued I should undoubtedly have died. These early accounts of ladrak, a Tibetan term that literally translates to “poison of the pass,” are not far removed from complaints of frontal headaches, lassitude, insomnia, and peripheral edema experienced by modern-day AMS sufferers. These symptoms usually resolve within 4 to 5 days but, if left untreated, may progress to the life-threatening malignant forms of high-altitude pulmonary and cerebral edema. Although the precise mechanisms of AMS and its related sequelae remain elusive, a low hypoxic ventilatory drive, water retention, and increased vascular permeability are recognized as the most important pathophysiologic factors.3 Arterial oxygenation decreases as a function of the hypobaria at terrestrial altitude, and thus tissue hypoxia is considered a trigger for these changes. The constellation of symptoms that characterizes AMS is a frequent cause of morbidity and occasionally mortality We recently participated in a medical expedition to the world's third highest mountain (K3), Kanchenjunga (8586 m [28,169 ft]), which was designed to increase knowledge and awareness of altitude-related illnesses. Our aims were to determine the physiologic implications of AMS and to establish constitutional risk factors that may be important in its pathogenesis. Specific attention focused on metabolic events that could result in changes in vascular permeability and the subsequent formation of edema. Our preliminary findings raise questions about the structural integrity of muscle or cardiac cell membranes at high altitude and its role in the pathogenesis of AMS. The source of membrane damage, which may be more pronounced in subjects presenting with AMS, may be linked to an increased activity of oxygen-free radicals. Changes in vascular function at high altitude as a consequence of increased free radical-mediated oxidative stress may also prove a topic worthy of investigation in the future. Whether increased susceptibility to membrane damage as the result of a deficient antioxidant defense system is the cause or consequence of AMS and related sequelae remains to be elucidated. Physical symptoms associated with upper respiratory and gastrointestinal tract illnesses are ubiquitous among mountaineers who ascend to high altitude. Although these illnesses may present without an infectious cause, the role of some potentially immunoprotective amino acids needs to be investigated. For example, previous accounts indicate a decrease in plasma glutamine concentrations at altitude,4 a conditionally essential amino acid required for optimal lymphocyte proliferation and macrophage phagocytosis.5 This decrease in plasma glutamine may increase a mountaineer's susceptibility to opportunistic infections. The subsequent release of vasoactive inflammatory mediators may be implicated in the pathogenesis of localized pulmonary edema, which would exacerbate arterial hypoxemia, physiologic phenomena that could account for at least some of the debilitating symptoms ascribed to AMS. We are currently conducting a double-blind placebo-controlled glutamine supplementation study in the Himalayas to explore further the possible link between infection and susceptibility to AMS. Cachexia, which is an almost inevitable consequence of high-altitude mountaineering, may also be related to possible changes in immunoreactivity and, although previously considered a maladaptive response, may prove to be of functional significance. The major sources of nitrogen for glutamine formation are the branched-chain amino acids, their metabolism being largely confined to skeletal muscle.6 A decrease in serum concentrations of the branched-chain amino acids previously observed at high altitude7 may signal for the endogenous catabolism of skeletal muscle to provide a constant supply of these amino acids and thus glutamine. The use of AMS prophylactics such as acetazolamide, which functions as a respiratory stimulant by inhibiting carbonic anhydrase, has become increasingly popular among mountaineers. Alternative strategies that incorporate nutritional supplementation with amino acids and antioxidants at high altitude may also prove useful in the battle against AMS. Understanding, preventing, and treating altitude illness remain a constant challenge for the mountain physiologist.