Comparing Integrative Respiratory and Renal Acid-Base Acclimatization in Lowlanders and Tibetan Highlanders During Incremental Ascent to 4,300m

Abstract

During sustained exposure to high altitude, integrated respiratory and renal acclimatization protects blood oxygenation and acid-base homeostasis, respectively. A sustained and augmented hypoxic ventilatory response (HVR) protects blood oxygenation with ascent (i.e., ventilatory acclimatization). However, the HVR elicits hypocapnia and respiratory alkalosis. A subsequent renally-mediated compensatory metabolic acidosis partially returns pH back to baseline values, with a high degree of variability, and capacity for full compensation limited to approximately 4000-4500m. In convenience samples of fully-acclimatized participants, indigenous highlanders of Tibetan ancestry (TH; i.e., Sherpa) have been reported to have (a) similar ventilatory acclimatization but, (b) improved renal compensation than lowlanders (LL) at 4300m. However, little work has been performed on the differences in renal acclimatization between LL and TH during acclimatization with incremental ascent to high altitude over a similar ascent profile. We assessed renal acclimatization between acclimatizing LL and TH, and hypothesized that (a) TH would have similar ventilatory acclimatization to LL but (b) larger magnitude renal compensation than LL during incremental ascent from 1400m to 4300m. Age- and sex-matched groups of 15 unacclimatized LL (8F) and 14 unacclimatized TH of confirmed Tibetan ancestry (7F) were recruited at 1400m. Utilizing an average of two finger capillary blood draw samples and a blood gas analyzer, we compared renally-mediated acid-base acclimatization (PCO2, [HCO3−], pH) in both groups before (1400m) and following day 8-9 of incremental ascent to 4300m. We found that following ascent, LL had significantly lower PCO2 (p<0.0001) and [HCO3-] (p<0.0001), and higher pH (P=0.0037), suggesting respiratory alkalosis and only partial renal compensation. However, TH had significantly lower PCO2 (p<0.0001) and [HCO3−] (p<0.0001), but unchanged pH (P=0.1), suggesting full renal compensation. At 4300m, TH had significantly lower PCO2 (P=0.01), [HCO3−] (p<0.0001) and pH (P=0.005) than LL. These data suggest that TH have larger magnitude and more rapid time-course ventilatory and renal mechanisms compared to LL, resulting in fully-compensated pH in TH during incremental ascent to high altitude, despite a larger hypocapnic stimulus. To our knowledge, this is the first study to demonstrate these integrated respiratory-renal responses between acclimatizing LL and TH. MRU, NSERC, NSF. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.