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Stewart's Strong Ion Difference

In 1981 Peter A. Stewart published his book How to understand acid-base - A quantitative acid-base primer for biology and medicine.. Two year later, in 1983, he published a paper also describing his concept of employing Strong Ion Difference as an alternative means of assessing clinical acid-base disturbances.

Now, some twenty eight years later, Stewart's Textbook of Acid-Base edited by John Kellum and Paul Elbers is available via acid-base.org and via Lulu Marketplace.

This page attempts to review the essentials of Stewart's approach as well as outlining the principal sources of criticism.

More Controversy:

Stewart's proposal provided one more source of acid-base controversy. The underlying science and rationale were less a source of criticism than were:

• The complexity of the chemistry and mathematics.
• Calculating small differences between large numbers with consequent lack of accuracy.
• [SID] only reflects plasma - unlike SBE which reflects the whole body and hemoglobin's influence.
• Lack of a clinical correlation to validate benefit.

Traditional Approach:

When we first study acid-base balance, it is too easy believe that the concentrations of the hydrogen and bicarbonate ions, [H⁺] and [HCO₃^-], are at the heart of the problem - are dominant forces. We do, after all, discuss them, measure them, and treat them: whatever an acid or a base does must be due to the pH, i.e., the concentration of H⁺. In addition [HCO₃^-] must surely determine the metabolic state.

Such thinking is obviously incorrect: in alkaline solutions there are almost no hydrogen ions present; so, whatever causes the evil behavior of an alkaline solution, the only thing that cannot be responsible is the hydrogen ion. And, clnically, both respiratory and metabolic changes affect the [HCO₃^-]. So, what is responsible for [H⁺] and [HCO₃^-]? Far from being central, or controlling, factors they actually depend on the concentrations of the other ions in solution. Although this should be apparent, it too often isn't. Stewart's method does re-emphasize these relationships.

Stewart's Dependent Variables:

Stewart listed a total of six ion concentrations as dependent: [H⁺], [OH^-], [HCO₃^-], [CO₃^--2], [HA], [A^-] (weak acids and ions). In-vivo and clinically, therefore, these are not subject to independent alteration. Their concentrations are governed by concentrations of other ions and molecules.

Stewart's Independent Variables:

There are three variables which are amenable to change in-vivo: partial pressure of carbon dioxide (PCO₂), total weak non-volatile acids [A_TOT], and net Strong Ion Difference [SID]. The influence of these three variables can be predicted through six simultaneous equations:

1. [H⁺] x [OH^-] = K '_w (water dissociation equilibrium)
2. [H⁺] x [A^-] = K_A x [HA] (weak acid)
3. [HA] + [A^-] = [A_TOT] (conservation of mass for "A")
4. [H⁺] x [HCO₃^-] = K_C x PCO₂ (bicarbonate ion formation equilibrium)
5. [H⁺] x [CO₃^2-] = K₃ x [HCO₃^-] (carbonate ion formation equilibrium)
6. [SID] + [H⁺] - [HCO₃^-] - [A^-] -[CO₃^2-] - [OH^-] = 0 (electrical neutrality)

Calculation:

Stewart showed that using the above equations, the concentration of each of the dependent variables was uniquely and independently determined by the three independent variables: PCO₂, [A_TOT], [SID]. The equations he derived were complex and involved 4^th order polynomials. Not surprisingly, Stewart used a computer to derive the effects of the three Independent Variables:

[SID]:

The Strong Ion Difference is the difference between the sums of concentrations of the strong cations and strong ions:

[SID] = [Na⁺] + [K⁺] + [Ca²⁺] + [MG²⁺] - [CL^-] - [Other Strong Anions].

[A_TOT]:

[A_TOT] is the total plasma concentration of the weak non-volatile acids, inorganic phosphate, serum proteins, and albumin:

[A_TOT] = [P_iTOT] + [Pr_TOT] + albumin.

PCO₂:

At the molecular level, it is clearly the concentration of CO₂, not the partial pressure, which governs its effect on other molecules and ions. In practice, however, our warm-blood status means solubility scarcely varies and we can use PCO₂ to measure carbon dioxide's effects.

Clinical Considerations:

Changes in acid-base status are either respiratory or non-repiratory, i.e., metabolic:

Respiratory:

The effects of changes on PCO₂ are well understood and produce the expected alterations in [H⁺]:

CO₂ + H₂O <—> H₂CO₃ <—> HCO₃^- + H⁺

Metabolic (Non-Respiratory):

Metabolic disturbances, obviously, cannot be viewed as a consequence of bicarbonate concentration because bicarbonate is merely a dependent variable. The two possible sources of metabolic, i.e., non-respiratory, disturbances are either [SID] or [A_TOT].

With normal protein levels, [SID] is about 40mEq/L. Any departure from this normal value is roughly equivalent to the standard base excess (SBE), i.e., if the measured [SID] were 45 mEq/L, the BE would be about 5 mEq/L, and a measured [SID] of 32 mEq/L would approximate to a BE = -8 mEq/L. Because [SID] does not allow for hemoglobin, there is often a discrepancy.

Changing [SID]:

[SID] can be changed by two principal methods:

1) Concentration:

Dehydration or over-hydration alters the concentration of the strong ions and therefore increases, or decreases, any difference. The body's normal state is on the alkaline side of neutral. Therefore, dehydration concentrates the alkalinity (contraction alkalosis) and increases [SID]; whereas, over-hydration dilutes this alkaline state towards neutral (dilutional acidosis) and decreases [SID].

2) Strong Ion Changes:

If the sodium concentration is normal, alterations in the concentration of other strong ions will affect [SID]:

a. Inorganic Acids:

The only strong ion capable of sufficient change is chloride, Cl^- (potassium, calcium and magnesium do not change significantly). An increased Cl^- concentration causes an acidosis and a decreased [SID]. Because the chloride ions are measured, the anion gap will be normal.

b. Organic Acids:

By contrast, if the body accumulates one of the organic acids, e.g., lactate, formate, keto-acids, then the metabolic acidosis is characterized by a normal chloride concentration and an abnormal anion gap because of the presence of the "unmeasured" organic acid.

Changing [A_TOT]:

The non-volatile weak acids comprise inorganic phosphate, albumin and other plasma proteins. Making the greatest contribution to acid-base balance are the proteins, particularly albumin, which behave collectively as a weak acid. Hypoproteinemia, therefore, causes a base excess and vice versa.

Phosphate levels are normally so low that a significant fall is impossible. However, in renal failure, high phosphate levels contribute to the acidemia.

Pros and Cons:

1) Understanding:

Stewart's greatest contribution may be his focus on the importance of the factors controlling pH. [H⁺], [OH^-] and [HCO₃^-] are merely dependent variable. This emphasis the importance of the underlying causes rightly diminishes the importance of the bicarbonate ion.

2) Calculation:

A major shortcoming lies in calculating a value for [SID] which depends upon accurate measurements of several variables. An acceptable level of error in the underlying measurements becomes less acceptable after subtraction. This is partly because the errors are summed and partly because any error now appears proportionately large against the resulting small value.

3) Standard Base Excess Accuracy:

Standard base excess has been well validated both for accuracy and for clinical relevance through many years of familiarity and clinical correlation. Although [SID] yields a somewhat similar numerical value to Base Excess, it does so with less reproducibility and accuracy and it neglects the influence of hemolobin as a buffer. Moreover, additional effort is required to obtain the result; and there is a smaller database of clinical correlation.

Conclusion:

For most acid-base disturbances, and for the foreseeable future, the traditional approach to acid-base balance seems certain to prevail. For the clinician, the three variables of greatest use are the pH, PCO₂, and standard base excess (SBE). What might change this? The answer would have to be published cases where clinical management has been critically improved by using Stewart's approach. Such cases would have to be accumulated, evaluated, and approved before any major switch to his approach seems warranted.

Acid-Base Tutorial Alan W. Grogono

Copyright Nov 2009. All Rights Reserved