7/28/2019 A Better Approach to Acid-Base Balance

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A Better Approach to Acid-Base Balance

Because hydrogen ions participate in so many reactions, understanding the chemistry of water and hydrogen ions is an

important part of the understanding of living systems. One interesting facet of human homeostasis is the tight control of

hydrogen ion concentration, [H+]. As metabolism creates about 300 liters of carbon dioxide each day, and as we also consume

about several hundred mEq of strong acids and bases in the same period, it is remarkable that the biochemical and feedback

mechanisms can maintain [H+] between 30 and 150 nanoEq/liter.

Appreciation of the physics and chemistry involved in the regulatory processes is essential for all life scientists,especially physiologists. Many physiology textbooks start the discussion of acid-base equilibrium by defining pH and thenfollow immediately with the Henderson-Hasselbach equation (6). While this leads rapidly to the usual diagrammatic approach,

the students understanding of the processes involved is frequently superficial and incomplete. Stewart (14,15) has criticized

this method and the central points of his critique were summarized by Reeves (11) as the failure to identify the independent

variables, the use of transformed variables (e.g., pH), and the use of outdated jargon (buffer base, for example). Fencl and

Leith (3) have also discussed the limitations of the traditional approach.

Stewart (14,15) proposed an alternate strategy that carefully specifies the independent variables, lists all the relevant

equations, and then solves the latter for the dependent variables. Stewart showed that with this approach the analysis of bodyfluids requires three independent variables: 1) the strong ion difference [SID], 2) the partial pressure of CO2, and 3) the total

concentration of weak acids (mainly protein in the case of plasma). See Figure 1. The analysis of chemistry of thesesubstances creates six equations that must be solved simultaneously (see p17). This approach, which is a specific application of

the general procedure given by Edsall and Wyman (2), provides an excellent model of blood plasma (9,20) and simplersolutions.

Stewart simplified the chemistry of plasma by lumping all the weak acids present there into a single substance which he

labeled A (for anion). This made understanding plasma acid-base balance much easier for beginners. There were problems,

however. The amount of A, Atot, and the value of As dissociation constant had to be obtained empirically. Secondly, the

model was inadequate if components of A changed in opposite directions, such as a protein decrease and a phosphate increase.

Consequently, others have strengthened Stewarts approach by treating the weak acid content of plasma more accurately.

Fencl and his coworkers (4,5) treated phosphate separately and included a very detailed treatment of serum albumin. Watson

(18) subsequently showed that this detail could be simplified with no appreciable loss of accuracy, and it is the Stewart-Fencl-

Watson model that is incorporated into AcidBasics II.

Having specified the values of the independent variables, the investigator of an acid-base system is left with the problem

of solving the equations. For many, however, this is a difficult task. Nomograms can be used (14) but they do not permitexact calculations, nor do they include the effects of changing weak acid concentrations. They also do not allow the

investigator to see the effects of changing the system parameters (dissociation constants, etc.). AcidBasics is a computer

program for desktop computers that solves these equations for a wide range of values of the independent variables and system

parameters.

To understand how the independent variables combine to determine [H+] in Stewarts model of plasma, students must

first understand the effects of the three independent variables in isolation. Stewart started with the simplest possible system,

pure water, and explored the effects of the addition of strong acids and bases on [H+] (14). He then introduced weak acids andbases and showed how they interact with [SID] to give [H+], etc. The effects of carbon dioxide and [SID] were introduced next

before all three processes were combined. In this movement from the simplest case to a model of blood plasma, the approachwas the same: specify the process, write out the equations, solve them, and explore the results. AcidBasics was designed to

facilitate this progressive approach.

AcidBasics II is much more than a teaching tool as it was designed with both students and researchers in mind. The

program is very flexible, almost every constant can be altered, and complex set-ups can be stored and reloaded.