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 [1]. 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 [2]
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 [3].
References
- ↑ Cumbo TA, Braude D, Basnyat B, Rabinowitz L, Lescano AG, Shah MB; et al. (2005). "Higher venous bicarbonate concentration associated with hypoxemia, not acute mountain sickness, after ascent to moderate altitude". J Travel Med. 12 (4): 184–9. PMID 16086892.
- ↑ Droma Y, Hanaoka M, Basnyat B, Arjyal A, Neupane P, Pandit A; et al. (2008). "Adaptation to high altitude in Sherpas: association with the insertion/deletion polymorphism in the Angiotensin-converting enzyme gene". Wilderness Environ Med. 19 (1): 22–9. doi:10.1580/06-WEME-OR-073.1. PMID 18333655.
- ↑ Droma Y, Hanaoka M, Basnyat B, Arjyal A, Neupane P, Pandit A; et al. (2006). "Genetic contribution of the endothelial nitric oxide synthase gene to high altitude adaptation in sherpas". High Alt Med Biol. 7 (3): 209–20. doi:10.1089/ham.2006.7.209. PMID 16978133.