The role of hemoglobin oxygen affinity in oxygen transport at high altitude

Hemoglobin is involved in the regulation of O2 transport in two ways: a long-term adjustment in red cell mass is mediated by erythropoietin (EPO), a response to renal oxgyenation. Short-term, rapid-response adjustments are mediated by ventilation, cardiac output, hemoglobin oxygen affinity (P50), barriers to O2 diffusion, and the control of local microvascular tissue perfusion. The distribution of O2 between dissolved (PO2PO2) and hemoglobin-bound (saturation) is the familiar oxygen equilibrium curve, whose position is noted as P50. Human hemoglobin is not genetically adapted for function at high altitude. However, more specialized species native to high altitudes (guinea pig and bar-headed goose, for example) seem to have a lower P50 than their sea level counterparts, an adaptation that presumably promotes O2 uptake from a hypoxic environment. Humans, native to very high altitude either in the Andes or Himalayan mountains, also can increase O2 affinity, not because of a fundamental difference in hemoglobin structure or function, but because of extreme hyperventilation and alkalosis.