Chemistry vs. compensation: Comparing integrated respiratory-renal 3 responses between acute inspired normobaric hypoxia vs. sustained 4 hypobaric hypoxia
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Issue Date
2025-06-17
Editor
Authors
Johnson, Nicole A.
Strzalkowski, Nicholas D.J.
Russell, Monica K.
Clermont, Christian A.
Demarty, Jennifer M.
Transfiguracion, Leo C.
Horton, John F.
Asmussen, Michael J.
Day, Trevor A.
Subject
Abstract
During acute exposure to hypoxia, peripheral respiratory chemoreceptors detect decreases in blood oxygenation, eliciting a hypoxic ventilatory response (HVR), which is enhanced with the duration and intensity of exposure (ventilatory acclimatization). The HVR protects oxygenation, but a secondary consequence is the elimination of PaCO2, resulting acutely in hypocapnia and respiratory alkalosis. With sustained exposure to hypobaric hypoxic conditions (e.g., high altitude ascent; HA), the renal tubules reduce HCO3- reabsorption and H+ excretion, excreting HCO3 - and retaining H+, returning arterial pHa toward normal values. We aimed to characterize and compare blood oxygenation and acid-base homeostasis between two models of hypoxic exposure with matching PIO2 (~74-76 mmHg): acute hypoxic exposure eliciting an HVR-mediated hypocapnia over 24-min vs. sustained hypoxic-hypocapnia with incremental ascent to HA over 10-days. Using arterial blood draws, we measured PaO2, SaO2, PaCO2, [HCO3 −]a and pHa, obtained before and following (a) acute stepwise reductions in FIO2 for ~24-min, with the last step being an FIO2 of 0.12 (PIO2≅74mmHg) and (b) sustained exposure to hypoxia during incremental ascent to 5,200m over 10-days (PIO2≅76mmHg). We found that (a) acute normobaric hypoxia elicited hypocapnia and respiratory alkalosis, as expected, and (b) after sustained exposure to hypobaric hypoxia, there was persistent alkalosis, despite appreciable renal compensation. These findings highlight the time-course and magnitude of integrated respiratory responses and subsequent renal compensation mounted by the kidneys, specifically that the hypoxia-mediated hypocapnia and respiratory alkalosis experienced at 5,200m is likely beyond the threshold for a full renal compensation in healthy lowlanders.
Description
This is an Accepted Manuscript version of an article that was originally published as: Johnson, N.A., Strzalkowski, N.D.J., Russell, M.K., Clermont, C.A., Demarty, J.M., Transfiguracion, L.C., Horton, J.F., Asmussen, M.J., & Day, T.D. (2025). Chemistry vs. compensation: Comparing integrated respiratory-renal 3 responses between acute inspired normobaric hypoxia vs. sustained 4 hypobaric hypoxia. Journal of Applied Physiology. https://doi.org/10.1152/japplphysiol.01014.2024