Dilutional acidosis: Where do the protons come from?

Purpose: To investigate the mechanism of acidosis developing after saline infusion (dilutional acidosis or hyperchloremic acidosis). Methods: We simulated normal extracellular fluid dilution by infusing distilled water, normal saline and lactated Ringer's solution. Simulations were performed either in a closed system or in a system open to alveolar gases using software based on the standard laws of mass action and mass conservation. In vitro experiments diluting human plasma were performed to validate the model. Results: In our computerized model with constant pKs, diluting extracellular fluid modeled as a closed system with distilled water, normal saline or lactated Ringer's solution is not associated with any pH modification, since all its determinants (strong ion difference, CO₂ content and weak acid concentration) decrease at the same degree, maintaining their relative proportions unchanged. Experimental data confirmed the simulation results for normal saline and lactated Ringer's solution, whereas distilled water dilution caused pH to increase. This is due to the increase of carbonic pK induced by the dramatic decrease of ionic strength. Acidosis developed only when the system was open to gases due to the increased CO₂ content, both in its dissociated (bicarbonate) and undissociated form (dissolved CO₂). Conclusions: The increase in proton concentration observed after dilution of the extracellular system derives from the reaction of CO₂ hydration, which occurs only when the system is open to the gases. Both Stewart's approach and the traditional approach may account for these results.