SIDa, SIDe and the strong ion gap
How SIG is calculated, why its reference range depends on the method, and which causes to consider when residual anionic charge is raised.
SIDa, SIDe and SIG measure different parts of the charge balance
Apparent strong ion difference (SIDa) is the measured strong-cation charge minus measured strong-anion charge. Effective strong ion difference (SIDe) is calculated bicarbonate plus albumin and phosphate charge. The strong ion gap (SIG) is the difference between them.
SIG estimates residual net charge that is not accounted for by the selected measured panel. A positive value represents residual anionic charge; a negative value represents residual cationic charge. It does not identify a substance.
The equations used here
- Measured strong ions
- SIDa = Na + K + 2Ca + 2Mg + Li − Cl − lactate − 2sulfate
- Albumin charge
- Alb⁻ = albumin in g/L × (0.123 × pH − 0.631)
- Phosphate charge
- Pi⁻ = phosphate × (0.309 × pH − 0.469)
- Effective strong ion difference
- SIDe = HCO₃⁻ + Alb⁻ + Pi⁻
- Residual gap
- SIG = SIDa − SIDe
Concentrations are in mmol/L except albumin; calculated charges are in mEq/L. Calcium must be ionised. The factor of two converts divalent ion concentration to charge equivalents. Phosphate charge is already included in the Figge equation and must not be doubled again.
Total magnesium is an approximation to strong-cation charge. Ionised magnesium can be selected when measured. Blank lithium and sulfate are omitted from the measured panel; any contribution remains in the residual gap.
What is a normal SIG?
The calculator starts with a conventional SIG screening range of 0–2 mEq/L. You can change it in the reference settings. This is a screening convention, not a universal laboratory interval or a UK/Australian national standard. Source: Herdman et al., 2015.
SIG depends on the electrolyte panel, magnesium convention, bicarbonate constants, albumin model and laboratory assays. A value above a conventional limit may therefore reflect method differences as well as residual anions. Use a method-matched local interval where available, and compare serial results obtained by the same method.
A high SIG alone does not establish metabolic acidosis, name an acid or indicate treatment. Read it with pH, SBE, compensation, measured contributors and the clinical course. The graph’s illustrative reference panel is a mathematical comparison, not a normal-SIG cutoff.
If SIG is raised, what should be considered?
First confirm the units, sample timing and assays. Lactate is already subtracted in SIDa, so a raised SIG is not another measure of the measured lactate.
- Ketoacids: diabetes, SGLT2 inhibitors, alcohol or prolonged poor intake. Measure blood ketones; glucose may be near normal.
- Renal anion retention: review kidney function, urine output and dialysis timing.
- Toxic metabolites: consider toxic alcohols or salicylates when the history or clinical pattern supports exposure. A normal osmolal gap does not exclude toxic alcohol poisoning.
- Other organic anions: short bowel suggests D-lactate; prolonged paracetamol use with malnutrition or renal impairment raises the possibility of 5-oxoproline.
For an unexpectedly low or negative SIG, recheck the method and measurements before attributing it to an unmeasured cation. Lithium is one possibility with a compatible exposure if it has not already been entered in the measured panel.
How does SIG differ from the anion gap?
The usual potassium-excluded anion gap is Na − Cl − HCO₃⁻. It includes albumin and measured lactate among the anionic contributions. Low albumin can conceal an increase in the uncorrected gap; this calculator also shows an albumin-corrected AG.
SIG explicitly accounts for albumin, phosphate, lactate and the other selected measured ions. AG and SIG therefore have different baselines and are not interchangeable. The simplified base-excess chart’s “other effects” residual is neither AG nor SIG.
Further reading
Sources
- Rocktaeschel et al. · Critical Care, 2003
Clinical strong-ion equations and charge-equivalent units.
- Morgan · The Stewart Approach, 2009
Physicochemical interpretation and unmeasured ions.
- Figge–Fencl · Albumin titration model
The pH-dependent albumin charge approximation.
Adult blood gases at 37°C. Use and limitations.