Physiologic changes: High altitude

Physiologic changes at altitude are primarily related to the decreased partial pressure of oxygen, rapid respiratory compensation, and slower metabolic compensation. Atmospheric pressure decreases non-linearly with increasing altitude, leading to a decrease in the partial pressure of O₂ (although FiO₂ remains relatively constant ~21% even at the highest altitudes). The initial physiologic response is mediated primarily by peripheral chemoreceptors and hypoxia. Acutely, respiratory compensation will begin to occur leading to increased respiratory rate, tidal volume, and minute ventilation, with subsequent respiratory alkalosis. The respiratory alkalosis leads to an acute leftward shift on the oxygen/hemoglobin dissociation curve, which is later moderated by metabolic acidosis and increased 2-3 DPG production.

Cardiovascular effects include an increase in heart rate with subsequent increase in cardiac output, resulting in increased oxygen delivery to the tissues. Plasma volume rapidly decreases (as much as 20%), leading to decreased preload and decreased stroke volume, as well as relative hemoconcentration. The metabolic response includes compensation for respiratory alkalosis by alkalization of urine (increased excretion of HCO₃-). Additional responses to hypoxia include increased production of erythropoietin leading to physiologic polycythemia (typically within a few weeks) and ultimately normalization of O₂ carrying capacity. Adequate compensation and acclimatization eventually leads to normalization of the initial hyperdynamic cardiovascular response.

Additional reported physiologic changes include increased capillary and mitochondrial density, although these findings have been disputed in more recent literature.