Altitude sickness pathophysiology

Overview
The pathophysiology underlying acute altitude sickness and excessive hypoxemia at high altitudes is not fully understood.

Pathophysiology
With ascent to altitude, subjects show some evidence of decreased effective circulating volume even without clinically significant changes. It is not clear whether decreased circulating volume is a significant risk factor in the development of acute mountain sickness at high altitude. There is a significant association between urinary measures of dehydration and bicarbonate retention in subjects developing excessive hypoxemia and acute altitude sickness at high altitudes. Oxygen saturation levels are strongly and inversely correlated with serum levels of venous bicarbonate and base excess, whereas acute mountain sickness and Lake Louise scores are not associated with these measures of alkalosis. It may be due to compromised ability of the kidney to metabolically compensate for an altitude-induced hypocapnic alkalosis.

Sherpas are well-known for their physical strength at high altitudes. They adapt to high altitude so well that little acute or chronic mountain sickness has been documented in them. The overrepresented I allele of the ACE gene in Sherpas might be one of the fundamental genetic factors responsible for maintaining physiological low-altitude ACE activity at high altitude, which may have an advantageous physiological role in adapting to a high-altitude environment

The wild alleles of the Glu298Asp and eNOS4b/a polymorphisms of the endothelial Nitric Oxide Synthase (eNOS) gene may be a benefit to the people living at high altitude (eg. sherpas) for adaptation.