Total weak acid concentration and effective dissociation constant of nonvolatile buffers in human plasma

The strong ion approach provides a quantitative physicochemical method for describing the mechanism for an acid-base disturbance. The approach requires species-specific values for the total concentration of plasma nonvolatile buffers (A_tot) and the effective dissociation constant for plasma nonvolatile buffers (K_a), but these values have not been determined for human plasma. Accordingly, the purpose of this study was to calculate accurate A_tot and K_a values using data obtained from in vitro strong ion titration and CO₂ tonometry. The calculated values for A_tot (24.1 mmol/l) and K_a (1.05 × 10^-7) were significantly (P < 0.05) different from the experimentally determined values for horse plasma and differed from the empirically assumed values for human plasma (A_tot = 19.0 meq/1 and K_a = 3.0 × 10^-7). The derivatives of pH with respect to the three independent variables [strong ion difference (SID), Pco₂, and A_tot] of the strong ion approach were calculated as follows: dpH/dSID⁺ = [1 + 10^(pKa-pH)]²/(2.303 × {SPco₂10^(pH-pKi)[1 + 10^(pKa-pH)]² + A_tot10^(pKa-pH)}); dpH/dPco₂ = S10^pKi/[2.303[A_tot10^pH(10^pH + 10^pKa)^-2 - SID⁺ 10^-pH]},dpH/dA_tot = -1/{2.303[SPco₂10^(pH-pKi) + SID ⁺10^(pKa-pH)]}, where S is solubility of CO₂ in plasma. The derivatives provide a useful method for calculating the effect of independent changes in SID⁺, Pco₂, and on plasma pH. The calculated values for A_tot and K_a should facilitate application of the strong ion approach to acid-base disturbances in humans.