The hematopoietic response to altitude was first observed in 1890 by Viault. We now know that within two hours of ascent to altitude, erythropoietin is increased in plasma and, over days to weeks, results in increased red cell mass. This adaptation has no importance during initial acclimatization when altitude illness develops and, when excessive, results in chronic mountain polycythemia. Shifts in the oxyhemoglobin dissociation curve are thought to be minimal in vivo at altitude, because the increase in 2,3-diphosphoglyceric acid, which is proportional to the severity of hypoxia and shifts the curve to the right, is offset by the respiratory alkalosis, which shifts the curve to the left. Naturally occurring left-shifted hemoglobin is an advantage at high altitude.

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