Anion Gap

Author: Cory Wilczynski, MD; Chief Editor: Eric B Staros, MD more...

Updated: Aug 2, 2012

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 of the anion gap is 3-11 mEq/L
The normal value for the serum anion gap is 8-16 mEq/L. However, there are always unmeasurable anions, so an
anion gap of less than 11 mEq/L using any of the equations listed in Description is considered normal.
For the urine anion gap, the most prominently unmeasured anion is ammonia. 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 ammonia (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).
[2]
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.
[3]
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.
[2]
A decreased anion gap (< 6 mEq/L) may suggest the following:
[4]
Hypoalbuminemia
Plasma cell dyscrasia

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Monoclonal protein
Bromide intoxication
Normal variant
A normal anion gap (6-12 mEq/L) may indicate the following:
[4]
Loss of bicarbonate (ie, diarrhea)
Recovery from diabetic ketoacidosis
Ileostomy fluid loss
Carbonic anhydrase inhibitors (acetazolamide, dorzolamide, topiramate)
Renal tubular acidosis
Arginine and lysine in parenteral nutrition
Normal variant
An elevated anion gap (>12 mEq/L; mud pilers) may indicate the following:
[4]
Milk-alkali syndrome
Uremia
Diabetic ketoacidosis
Propylene glycol
Isoniazid intoxication
Lactic acidosis
Ethanol ethylene glycol
Rhabdomyolysis/renal failure
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).
[1]
Methodology: Anytime, nonfasting, venous sample
Reported: Within 30 minutes
Collection: Green (sodium or lithium heparin), plasma, or serum separator tube
Storage/transport temperature: Refrigerated.
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.
[5]
Serum anion gap = (Na + K) - (Cl + HCO3)
Commonly, a 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,
Anion Gap http://emedicine.medscape.com/article/2087291-overview?src=medsc...
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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.


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Contributor Information and Disclosures
Author
Cory Wilczynski, MD Resident Physician, Department of Internal Medicine, St Louis University School of
Medicine
Disclosure: Nothing to disclose.
Chief Editor
Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical
Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital
Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society
for Clinical Pathology, Association for Molecular Pathology, and College of American Pathologists
Disclosure: Nothing to disclose.
References
Basic Metabolic Panel: ARUP Lab Tests. ARUP Laboratories: National Reference Laboratories. 2006-2012.
Available at http://www.aruplab.com/.
1.
Criner, GJ. "Metabolic Disturbance of Acid-Base and Electrolytes.". In: Critical Care Study Guide: Text and
Review. 2
nd
ed. Philadelphia, PA: Springer; 2010:696.
2.
"Anion gap - Wikipedia, the free encyclopedia." N.p., 18 May 2012. Web. 20 May 2012. Wikipedia, the free
encyclopedia. Available at http://en.wikipedia.org/wiki/Anion_gap.
3.
Cho KC. Chapter 21. Electrolyte & Acid-Base Disorders. In: McPhee SJ, Papadakis MA, Rabow MW, eds.
CURRENT Medical Diagnosis & Treatment 2012. New York: McGraw-Hill; 2012:[Full Text].
4.
Emmet, M. The anion gap/HCO3 ratio in patients with a high anion gap metabolic acidosis. In: Stern RH (ed).
UpToDate. Waltham, MA: UpToDate; June 17 2010.
5.
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