Strong ion difference: Etiology

Strong ions are cations and anions that exist as charged particles dissociated from their partner ions at physiologic pH. Thus, these ions are “strong” because their ionization state is independent of pH. The Strong Ion Difference (SID) is the difference between the positively- and negatively-charged strong ions in plasma. This method of evaluating acid-base disorders was developed to help determine the mechanism of the disorder rather than simply categorizing them into metabolic vs. respiratory acidosis/alkalosis as with the Henderson-Hasselbalch equation.

Strong cations predominate in the plasma at physiologic pH leading to a net positive plasma charge of approximately +40-45. SID can be estimated as follows:

SID = [strong cations] – [strong anions] = [Na+ + K+ + Ca2+ + Mg2+] – [Cl- + lactate-]

Disturbances that increase the SID increase the blood pH (alkalosis) while disorders that decrease the SID lower the plasma pH (acidosis).

According to the law of electroneutrality the sum of positive charges is equal to the sum of negative charges. Therefore the SID must be equal to the sum of weak anions in the body (such as bicarbonate, albumin, and phosphate).

Increased SID may be caused by:

  • Dehydration (contraction alkalosis) due to increased Na+
  • Chloride loss (e.g. aggressive NG suctioning with loss of HCl)

Decreased SID may be caused by:

  • Free water excess (dilutional acidosis) due to decreased Na+
  • Aggressive administration of Normal Saline (NS) as the SID of Normal Saline is 0 (Na+ = 154mEq/L and Cl- = 154mEq/L → SID = 154 – 154 = 0)
  • Severe diarrhea due to loss of K+ and Na+
  • An increase in unmeasured anions such as lactate (e.g. lactic acidosis) or ketoacids (e.g. diabetic ketoacidosis)


Keyword history



  1. Neligan PJ, Deutschman CS. Perioperative Acid-Base Balance. In: Miller RD, Eriksson LI, Fleisher L, Wiener-Kronish JP, Cohen NH. Miller’s Anesthesia, 8th ed. Philadelphia, PA: Elsevier Saunders; 2014: Ch. 60, pp. 1811-1829


  1. Kellum JA. Determinants of blood pH in health and disease. Critical Care, 2000, 4:6–14. PubMed PMID: 835845.

Defined by: Katie Forkin, MD