High Altitude Medicine: Understanding the Mechanism of Acute Mountain Sickness

The present study was undertaken to determine the integrative physiology behind acute mountain sickness (AMS) susceptibility. We compared the respiratory, cardiovascular, renal and cerebrovascular responses to acute hypoxia. 28 people (14 females; age 24 ± 7 years) were exposed to normobaric hypoxia (HA, FiO2: 12.5%, PiO2: 88.6mmHg) and normoxia (SL, FiO2: 21%, PiO2: 148.8mmHg) for 10 hours. Repeated measurements were made of AMS symptoms, respiratory, cardiovascular, renal and cerebrovascular variables. Compared to SL, HA induced an increase in ventilation (p < 0.001). This caused a respiratory alkalosis (p < 0.001) which was compensated for by an increased bicarbonate (p < 0.001) and cation excretion (Na+: p = 0.048, K+: p < 0.001). Fluid balance varied between individuals based on their level of renal compensation (p = 0.519). Cerebral blood flow increased (p < 0.001), cerebral autoregulation was impaired (VLF coherence: p < 0.001, VLF nGain: p = 0.026, VLF phase: p < 0.001) and cerebrovascular CO2 reactivity was enhanced (p < 0.001). We calculated slopes of change in every variable over the HA exposure and correlated these to the change in AMS score. Those who were more susceptible to AMS showed a greater increase in ventilatory response (p < 0.020) This caused a decrease in heart rate over time (p = 0.040), and a more severe alkalosis (p = 0.001). They had an increase in weight (p = 0.005), venous bicarbonate concentration (p = 0.047) and venous sodium concentration (p = 0.001) indicating an antidiuresis, intravascular fluid shift and fluid retention. The flow through the vertebral artery increased more in those who were more susceptible due to an increased diameter (p < 0.001). Cerebral autoregulation impairment was not greater in those with AMS. Cerebrovascular CO2 reactivity decreased over the day in susceptible individuals (p = 0.029) due to their increased pH and bicarbonate concentration. The change in vertebral artery diameter (p = 0.001) and venous pH (p = 0.001) were strong predictors of the change in AMS score (R2 = 0.605). These results indicate that vertebral artery hyperfusion and inadequate renal compensation augmenting venous pH may play a key role in the pathogenesis of AMS during acute exposure to hypoxia