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.
Highlights
A natural starting point in understanding acid-base is to seek an explanation that pH in any specified fluid has exactly the observed value
We investigated possible sources of variance between measured and modeled pH using Eq 7 to find the concentration of an unknown buffer with an arbitrary pKa of 7, or if the fitted weak acid had a negative concentration, it was set to 0, and a weak base was fitted using a pKb of 6 to give a perfect fit
The theoretical validity of Eq 7 is indisputable from physical chemistry, with the minor addition of charges on albumin as empirically verified by Watson [13]
Summary
A natural starting point in understanding acid-base is to seek an explanation that pH in any specified fluid has exactly the observed value. Strong Relationships in Acid-Base disorders can be formulated in terms of the conditions determining pH. Looking back, this ambition is not new. Brown et al [1] wrote in 1989 “In analysis of acid-base balance, one must keep in mind the fact that electroneutrality dictates that the sum of the charges of the nonreactive ions in urine ([Na+]+[K+]-[Cl-]) must be equal and opposite in signs to the sum of charges of buffer ions plus organic ions. The contribution of urinary excretion to systemic acid-base balance can be assessed either by measuring the buffer plus organic ions or the nonreactive ions in urine”
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