Date Published: September 15, 2016
Publisher: Public Library of Science
Author(s): Troels Ring, John A. Kellum, Yeng-Tseng Wang.
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.
A natural starting point in understanding acid-base is to seek an explanation that pH in any specified fluid has exactly the observed value. If that is possible, mechanisms in acid-base disorders can be formulated in terms of the conditions determining pH. Looking back, this ambition is not new.
The theoretical validity of Eq 7 is indisputable from physical chemistry, with the minor addition of charges on albumin as empirically verified by Watson . However the demonstration that Eq 7 has utility in a clinical dataset is a demanding task. A very simple illustration of the problem on which we are focusing is presented in Figs 1 and 2, handling just the mixing 1:1 of two fluids, in which the [H+] cannot be predicted from averaging [H+] but is solely determined by SID.