Chemistry vs. compensation: Comparing integrated respiratory-renal responses between acute inspired normobaric hypoxia vs. sustained hypobaric hypoxia.

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 P_IO₂ (~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 F_IO₂ of 0.12 (P_IO₂≅74mmHg) and (b) sustained exposure to hypoxia during incremental ascent to 5,200m over 10-days (P_IO₂≅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.