Reference Range
The anion gap is the difference between primary measured cations (sodium Na+ and potassium K+) and the primary measured anions (chloride Cl- and bicarbonate HCO3-) in serum. This test is most commonly performed in patients who present with altered mental status, unknown exposures, acute renal failure, and acute illnesses. [1] See the Anion Gap calculator.
The reference range for the anion gap is as follows: [2]
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16 ± 4 mEq/L (if the calculation employs potassium)
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12 ± 4 mEq/L (if the calculation does not employ potassium)
For the urine anion gap, the most prominently unmeasured cation is NH4+. Healthy subjects typically have a gap of 0 to slightly normal (< 10 mEq/L). A urine anion gap of more than 20 mEq/L is seen in metabolic acidosis when the kidneys are unable to excrete NH4+ (such as in renal tubular acidosis). If the urine anion gap is zero or negative but the serum AG is positive, the source is most likely gastrointestinal (diarrhea or vomiting). [3]
Interpretation
The anion gap (see the Anion Gap calculator) can be defined as low, normal, or high. Laboratory error always needs to be ruled out first if the clinical picture does not correlate with the findings. Thus, if the results are questionable, re-assessing the electrolytes is the encouraged first step.
Certain errors in collection can interfere with the ions of measured electrolytes that are used to calculate the anion gap. This can include timing, dilution, renal disease, and small sample size. For example, delays in processing the collected sample results in continued leukocyte cellular metabolism, which then causes an increase in bicarbonate levels. [4]
If the anion gap is found to be high, other tests such as urine ketones, serum ketones (beta-hydroxybutyrate), serum lactic acid, urine drug screen, serum drug screen, salicylate level, and creatinine kinase level should also be performed to diagnose the etiology of the anion gap acidosis.
The urine anion gap is either positive or negative and can be used when the causes of normal anion gap acidosis are unclear. A positive urine anion gap is seen in conditions of type 1 and type 2 renal tubular acidosis versus almost every other cause of normal anion gap acidosis (diarrhea). The limiting factor of urine anion gap equation is that it is valid only if the urine sodium level is less than 20mEq/L. [3]
A decreased anion gap (< 6 mEq/L) may suggest the following [5] :
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Plasma cell dyscrasia
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Monoclonal protein
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Bromide intoxication
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Normal variant
A normal anion gap (6-12 mEq/L) may indicate the following [5] :
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Loss of bicarbonate (ie, diarrhea)
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Recovery from diabetic ketoacidosis
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Ileostomy fluid loss
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Carbonic anhydrase inhibitors (acetazolamide, dorzolamide, topiramate)
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Renal tubular acidosis
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Arginine and lysine in parenteral nutrition
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Normal variant
An elevated anion gap (>12 mEq/L; “mud pilers”) may indicate the following [5] :
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Methanol
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Propylene glycol
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Isoniazid intoxication
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Ethanol ethylene glycol
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Rhabdomyolysis/renal failure
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Salicylates
Collection and Panels
To calculate the serum anion gap, all components can be drawn in a basic metabolic panel (which includes calcium, carbon dioxide, chloride, creatinine, glucose, potassium, sodium, and urea nitrogen), as follows [1] :
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Methodology: Anytime, nonfasting, venous sample
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Reported: Within 30 minutes
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Collection: Green (sodium or lithium heparin), plasma, or serum separator tube
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Storage/transport temperature: Refrigerated.
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Unacceptable conditions: Specimens collected in ethylenediaminetetraacetic acid, citrate, or oxalate.
To calculate the urine anion gap, the urine electrolytes sodium, chloride, and potassium are measured. This can be done under the same conditions as any urinalysis.
Background
Definition
The anion gap is the difference between primary measured cations (sodium Na+ and potassium K+) and the primary measured anions (chloride Cl- and bicarbonate HCO3-) in serum. The equation itself is used as an estimate to measure the unmeasurable anions in blood. The following equation is used to calculate the serum anion gap [6] :
Serum anion gap = (Na + K) - (Cl + HCO3)
Commonly, the following simpler formula is used, as sodium is the most dominant cation in the equation below (see also the Anion Gap calculator):
Serum anion gap = Na - (Cl + HCO3)
The anion gap can also be used to differentiate cations and anions in urine using the following equation:
Urine anion gap = Na+ + K+ - Cl−
Indications/Applications
Anion gap is most commonly performed for patients who present with altered mental status, unknown exposures, acute renal failure, and acute illnesses. [1]
Considerations
Laboratory error always needs to be ruled out first if the clinical picture does not correlate with the findings. Thus, if the results of the anion gap are questionable, re-assessing the electrolytes is the encouraged first step.
