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Rational treatment and thorough diagnostic classification of acid-base disorders requires quantitative understanding of the mechanisms that generate and dissipate loads of acid and base. A natural precondition for this tallying is the ability to quantify the acid content in any specified fluid. Physical chemistry defines the pH-dependent charge on any buffer species, and also on strong ions on which, by definition, the charge is pH-invariant. Based, then, on the requirement of electroneutrality and conservation of mass, it was shown in 1914 that pH can be calculated and understood on the basis of the chemical composition of any fluid. Herein we first show that this specification for [H + ] of the charge-balance model directly delivers the pH-dependent buffer-capacity as defined in the literature. Next, we show how the notion of acid transport as proposed in experimental physiology can be understood as a change in strong ion difference, ΔSID. Finally, based on Brønsted-Lowry theory we demonstrate that by defining the acid content as titratable acidity, this is equal to SID ref  – SID, where SID ref  is SID at pH 7.4. Thereby, any chemical situation is represented as a curve in a novel diagram with titratable acidity = SID ref  – SID as a function of pH. For any specification of buffer chemistry, therefore, the change in acid content in the fluid is path invariant. Since constituents of SID and titratable acidity are additive, we thereby, based on first principles, have defined a new framework for modeling acid balance across a cell, a whole organ, or the whole-body.

Acid content and buffer-capacity: a charge-balance perspective