These two populations have adapted to the same environmental pressure in a genetically different way. Andean populations, if suddenly brought to high altitudes, can suffer an attenuated form of HVR, while Tibetans have a chronic form of HVR that allows them to breathe more air per unit of time. The body exposed to high altitudes reacts with a form of hyperventilation known as HVR (hypoxic ventilatory response). The evolutionary pathway traveled by the Andeans increased their hemoglobin levels and selected a series of mutations in genes linked to the morphology of the cardiovascular system to make it more efficient in these subjects, resulting in very viscous blood (high level of hematocrit is a risk factor for the development of “chronic altitude sickness” CMS). The Andeans show a concentration of hemoglobin strongly dependent on altitude, in contrast to the Tibetans. Regarding geographically isolated human populations, such as Tibetans and Andeans, who have a relatively different genetic basis, living for millennia in a very similar environment, they are under comparable selective pressure. It is most often seen in South Americans because of their poorer adaptation to the top altitude, which is probably due to the change in blood volume and the remodeling of the pulmonary arterioles with smooth muscle cell expansion, thus generating excessive pulmonary arteriole pressure upon the re-ascent to a high altitude. This phenomenon has not been reported in Sherpa or other people from Tibet in Nepal or India. A subgroup of HAPE, re-entry HAPE is a well-known life-threatening illness that has been recorded almost exclusively in North and South America. It appears necessary to underline and add that, in some specific subpopulations, following the previous stay at sea level, HAPE re-entry pulmonary edema (HAPE) can occur. Such an approach is critical for the effective treatment of patients in a hostile environment, or treatment in the emergency room after exposure to extreme physical or environmental factors. With a deeper understanding of the pathogenesis of high-altitude diseases, as well as a reasoned approach to environmental or physical factors, we examine the main high-altitude diseases. The third section focuses on high-altitude pulmonary edema, which is one of the main high-altitude diseases. Early recognition of clinical symptoms is important for the establishment of the correct therapy. The second section discusses the main high-altitude diseases, highlighting how environmental factors can lead to the loss of homeostasis, compromising important vital functions. The first section of our work defines high altitude and considers the mechanisms of adaptation to it and the associated risk factors for low adaptability. This paper aims to provide a comprehensive review of high-altitude sickness, including its epidemiology, pathophysiology, and treatments. High altitude can be a hostile environment and a paradigm of how environmental factors can determine illness when human biological adaptability is exceeded.
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