In vitro characterization of hemoglobin oxygen dissociation curves and electrolyte shifts in human blood under varying PCO2

Background Efficient oxygen transport depends on hemoglobin (Hb) affinity for O 2 , which is modulated by factors like PCO 2 , as described by the Bohr effect. This in vitro study explored how varying PO 2 and PCO 2 influence hemoglobin oxygen saturation (HbO 2 ) and plasma electrolyte concentrations in whole human blood. Methods Blood from six healthy volunteers was equilibrated at 37°C with gas mixtures spanning PO 2 and PCO 2 ranges. A total of 346 samples were analyzed for blood gases, HbO 2 , and electrolytes. The HbO 2 dissociation curve was modeled using a Gompertz function within a non-linear mixed-effects framework, while electrolyte dynamics were assessed via polynomial models. Results HbO 2 saturation ranged from 1.4 to 99.6%. Increasing PCO 2 shifted the dissociation curve rightward, steepening its slope and raising the inflection point—hallmarks of the Bohr effect—without affecting maximal HbO 2 . Electrolyte analysis revealed that chloride decreased with PCO 2 and increased with HbO 2 , consistent with the erythrocyte chloride shift. Sodium increased with PCO 2 , and a significant interaction between HbO 2 and PCO 2 was observed. Strong ion difference (SID) decreased linearly with HbO 2 and increased quadratically with PCO 2 , suggesting a compensatory role in CO 2 -induced acid-base changes. Conclusion These findings, validated against external datasets, underscore the tight coupling between respiratory gas exchange and electrolyte homeostasis. The study provides novel insights into how CO 2 modulates both oxygen delivery and plasma ionic composition, with implications for understanding acid-base physiology and its regulation in health and disease.