Strong Relationships in Acid-Base Chemistry – Modeling Protons Based on Predictable Concentrations of Strong Ions, Total Weak Acid Concentrations, and pCO2

Abstract

Understanding acid-base regulation is often reduced to pigeonholing clinical states into categories of disorders based on arterial blood sampling. An earlier ambition to quantitatively explain disorders by measuring production and elimination of acid has not become standard clinical practice. Seeking back to classical physical chemistry we propose that in any compartment, the requirement of electroneutrality leads to a strong relationship between charged moieties. This relationship is derived in the form of a general equation stating charge balance, making it possible to calculate [H+] and pH based on all other charged moieties. Therefore, to validate this construct we investigated a large number of blood samples from intensive care patients, where both data and pathology is plentiful, by comparing the measured pH to the modeled pH. We were able to predict both the mean pattern and the individual fluctuation in pH based on all other measured charges with a correlation of approximately 90% in individual patient series. However, there was a shift in pH so that fitted pH in general is overestimated (95% confidence interval -0.072–0.210) and we examine some explanations for this shift. Having confirmed the relationship between charged species we then examine some of the classical and recent literature concerning the importance of charge balance. We conclude that focusing on the charges which are predictable such as strong ions and total concentrations of weak acids leads to new insights with important implications for medicine and physiology. Importantly this construct should pave the way for quantitative acid-base models looking into the underlying mechanisms of disorders rather than just classifying them.

Modeling Acid–Base by Minimizing Charge-Balance

“…Problems with measurements of every item including pH were expected, and the presence of unmeasured anions and cations were considered likely. 2 The ionic strength was, as typical for clinical samples, high around 0.15, and correspondingly, the single-charge activity coefficients about 0.733, that is far from 1.…”

“…Modeling pH was accomplished based on a set of 2437 values found in Ring 2 by way of the thermodynamic dissociations corrected for ion strength and taking the measured pH to be −log( a H + ). 24 This was a sample from critically ill but very heterogenous patients, and the modeling was based on all of the nine measured moieties, corresponding to 13 different charges (see “Derivation of the charge-balance model” in the Supporting Information).…”

“…Also, some of the results from Tessman and Ivanov 5 are presented and analyzed to further expose the consequences of disagreement in assessing the equilibrium conditions. Furthermore, we modeled a set of previously examined 2 clinically obtained pH values on the basis of electrolyte, albumin, phosphate, lactate, and p CO 2 values. Finally, analyses of the papers by Glaser et al 18 and Baeza-Baeza and García-Álvarez-Coque 7 are presented in brief.…”

Modeling amount of acid

“…Dr. Ring nicely describes the importance of accounting for titratable acidity of biologic fluids in a recent publication from his laboratory. 5 We agree with Dr. Ring that providing a more complete panel of the relevant acid-base parameters, including titratable acidity, of the microdialysate would have been needed if our goal had been to precisely measure tissue acid content. Instead, our goal was to assess directional and quantitative changes in tissue acid content in response to the described interventions compared with an established baseline.…”

Reply by Cove and Kellum to Swenson

“…We flatly reject the assertion that teaching the Stewart approach is difficult or that it leads to increased costs and blood loss. In fact, the variables needed to apply the approach are routinely measured already ( 6 ). The value of the approach comes from the ability to understand the relative contributing effects of simultaneous abnormalities on the final observed pH, such as elevated lactate, hypoalbuminemia, and electrolyte abnormalities, in a way that bicarbonate-centric understanding cannot ( 7 ).…”