Strong Ion Difference

Strong Ion Difference: … amount by which the strong positive ions (cations) are in excess of the strong negative ions (anions).

Chawla, G., 2008


In 1981 Peter A. Stewart published his book How to understand acid-base – A quantitative acid-base primer for biology and medicine.. Two years 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 thirty-five years later, Stewart’s Textbook of Acid-Base edited by John Kellum and Paul Elbers is available via and via Lulu Marketplace.

Stewart’s approach has been critically reviewed by Morgan. In Addition Rastegar published a valuable summary indicating that SID is of benefit only infrequently. Below is a review of the essentials of SID as well as an outline of the principal sources of criticism.

More Controversy:

Stewart’s proposal provided several sources of acid-base controversy. The underlying science and rationale were less a source of criticism than were:

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

Traditional Approach:

It is too easy to believe that the concentrations of the hydrogen and bicarbonate ions, [H+] and [HCO3], are at the heart of the problem: we discuss them, measure them, and treat them! whatever an acid or a base does must surely be due to the pH, i.e., the concentration of H+.

Such thinking is transparently incorrect: in alkaline solutions, like plasma, there are virtually 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, clinically, 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. This should be obvious and Stewart’s method serves to re-emphasize these relationships.

Stewart’s Dependent Variables:

[H+] [OH]
[HCO3] [CO32-]
[HA]  [A]

Stewart listed a total of six ion concentrations as dependent: [H+], [OH], [HCO3], [CO32-], [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 [ATOT], 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] = 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)