Acute mountain sickness: Do different time courses point to different pathophysiological mechanisms?

Abstract

Acute mountain sickness (AMS) is a syndrome of nonspecific symptoms (i.e., headache, anorexia, nausea, vomiting, dizziness, and fatigue) that may develop in nonacclimatized individuals after rapid exposure to altitudes ≥2,500 m. In field studies, mean AMS scores usually peak after the first night at a new altitude. Analyses of the individual time courses of AMS in four studies performed at 3,450 m and 4,559 m revealed that three different patterns are hidden in the above-described overall picture. In 41% of those who developed AMS (i.e., AMS-C score >0.70), symptoms peaked on day 1, in 39%, symptoms were most prominent on day 2, and in 20%, symptoms were most prominent on day 3. We suggest to name the different time courses of AMS type I, type II, and type III, respectively. Here, we hypothesize that the variation of time courses of AMS are caused by different pathophysiological mechanisms. This assumption could explain why no consistent correlations between an overall assessment of AMS and single pathophysiological factors have been found in a large number of studies over the past 50 yr. In this paper, we will briefly review the fundamental mechanisms implicated in the pathophysiology of AMS and discuss how they might contribute to the three different AMS time courses.

Cardio-respiratory, oxidative stress and acute mountain sickness responses to normobaric and hypobaric hypoxia in prematurely born adults

“…One could speculate that the discrepancy between the studies could be attributed to either the differences in the employed exposure durations (Debevec and Millet 2014) or the differences in the individual responses (Luks et al 2017). In regards to the latter, a recent analysis by Berger et al (2019) suggested that individuals with a lower/blunted hypoxic ventilatory drive, a prominent feature in prematurely born individuals, might fully develop AMS only following nocturnal hypoxic exposure (e.g., on the second exposure day). They speculated that the late occurrence of AMS in these individuals might be predominantly related to greater nocturnal desaturation (Berger et al 2019).…”

“…In regards to the latter, a recent analysis by Berger et al (2019) suggested that individuals with a lower/blunted hypoxic ventilatory drive, a prominent feature in prematurely born individuals, might fully develop AMS only following nocturnal hypoxic exposure (e.g., on the second exposure day). They speculated that the late occurrence of AMS in these individuals might be predominantly related to greater nocturnal desaturation (Berger et al 2019). This hypothesis should be further explored in prematurely born population during prolonged (multi-day) altitude exposure combined with comprehensive polysomnography assessment.…”

Downregulation of lung miR-203a-3p expression by high-altitude hypoxia enhances VEGF/Notch signaling

“…Hypoxia is the most critical cause of acute mountain sickness (AMS) [1,2]. At high-altitude environments (above 2,500 meters) air oxygen levels remain constant, but as the altitude increases the oxygen partial pressure (PaO2) drops [3,4].…”

No Relevant Analogy Between COVID-19 and Acute Mountain Sickness

“…This time course is significantly longer than the time course with which AMS develops. Usually, AMS symptoms develop 4-12 hours after arrival at a new altitude (Berger et al, 2019). This discrepancy in the time courses from the initial ''insult'' (i.e., infection vs. ascent to high altitude) to the onset of symptoms indicates distinct pathophysiological mechanisms, even if some clinical manifestations of AMS may be similar to those experienced during COVID-19 (i.e., hypoxemia, fatigue, and nausea).…”