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FIGURE 13.1 Ambient oxygen levels, measured by the partial pressure of oxygen (solid line) or as a percent of sea-level values (dashed line), decrease with increasing altitude, a situation called high-altitude or hypobaric hypoxia. The atmosphere contains ≈21% oxygen at all altitudes.

≥2,500 m, where physiological effects become more easily detectable with more severe stress. Many studies report about populations living in the range of 3,500–4,500 m, because many people live in that altitude range on both plateaus, and because those residents must deal with severe stress and may be most likely to exhibit adaptive responses. At 4,000-m elevation, every breath of air contains only ≈60% of the oxygen molecules in the same breath at sea level. This is a constant feature of the ambient environment to which every person at a given altitude is inexorably exposed. Less oxygen in inspired air results in less oxygen to diffuse into the bloodstream to be carried to the cells for oxygen-requiring energy-producing metabolism in the mitochondria. Humans do not store oxygen, because it reacts so rapidly and destructively with other molecules. Therefore, oxygen must be supplied, without interruption, to the mitochondria and to the ≥1,000 oxygen-requiring enzymatic reactions in various cells and tissues (Raymond and Segre, 2006).

The oxygen level is near zero in human mitochondria at all altitudes (Hochachka and Rupert, 2003). This condition is described as “primitive,” because it has changed little for the past 2.5 billion years despite wide swings in the amount of atmospheric oxygen (at times it has been 10,000-fold lower; Bekker et al., 2004; Huey and Ward, 2005) and “protective” in the sense that it circumvents potentially damaging reactions of oxygen with other molecules (Massabuau, 2003). Fig. 13.2 describes the transport of oxygen in humans along a “cascade” of falls in oxygen level from inspired air to the capillaries from which it will diffuse into the mito-

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