7/19/13 Acid-Base Tutorial - Strong Ion Difference

by "Grog" (Alan W. Grogono), Professor Emeritus, Tulane Univ ersity Department of Anesthesiology

Stewart's Strong Ion Difference

Home Page
Terminology In 1981 Peter A. Stewart published his book How to understand acid-
History base - A quantitative acid-base primer for biology and medicine..
Physiology Two year later, in 1983, he published a paper also describing his
Acid Production concept of employing Strong Ion Difference as an alternative means
pH Playground of assessing clinical acid-base disturbances.
Henderson Eqn. Now, some twenty eight years later, Stewart's Textbook of Acid-Base edited by John
Acid-Base Diagram Kellum and Paul Elbers is available via acid-base.org and via Lulu Marketplace.
Clinical Aspects
This page attempts to review the essentials of Stewart's approach as well as outlining
Resp. Acid/Alk
the principal sources of criticism.
Metab. Acid/Alk
Interpretation More Controversy:
Simple Arithmetic Stewart's proposal provided one more source of acid-base controversy. The underlying
Strong Ion Diffnce. science and rationale were less a source of criticism than were:
Plastic Cards The complexity of the chemistry and mathematics.
Computing Methods Calculating small differences between large numbers with consequent lack of
Alphabetical Index accuracy.
Links [SID] only reflects plasma - unlike SBE which reflects the whole body and
References hemoglobin's influence.
Testimonials Lack of a clinical correlation to validate benefit.
About the Author Traditional Approach:
Donations When we first study acid-base balance, it is too easy believe that the concentrations of
Contact 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.

[H+] [OH-]
Stewart's Dependent Variables:
[HCO3 -] [CO3 2-]Stewart listed a total of six ion concentrations as dependent: [H+],
[HA] [A-] [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:

PCO2
There are three variables which are amenable to change in-vivo: partial
pressure of carbon dioxide (PCO2), total weak non-volatile acids [ATOT], and [ATOT ]
net Strong Ion Difference [SID]. The influence of these three variables can be [SID]
predicted through six simultaneous equations:
1. [H+] x [OH-] = K 'w (water dissociation equilibrium)
+ -
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w
+ -
2. [H ] x [A ] = KA x [HA] (weak acid)
3. [HA] + [A-] = [ATOT] (conservation of mass for "A")
4. [H+] x [HCO3-] = KC x PCO2 (bicarbonate ion formation equilibrium)
5. [H+] x [CO32-] = K3 x [HCO3-] (carbonate ion formation equilibrium)
6. [SID] + [H+] - [HCO3-] - [A-] -[CO32-] - [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, [ATOT], [SID]. The equations he derived were complex and
involved 4th 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].
[ATOT]:
[ATOT] is the total plasma concentration of the weak non-volatile acids, inorganic
phosphate, serum proteins, and albumin:
[ATOT] = [PiTOT] + [PrTOT] + 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 [ATOT].
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
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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 [ATOT]:
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 Copyright Oct 2011.

Alan W. Grogono All Rights Reserved

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