Type of test Blood
Normal findings
16 ± 4 mEq/L (if potassium is used in the calculation)
12 ± 4 mEq/L (if potassium is not used in the calculation)
Test explanation and related physiology
The anion gap (AG) is the difference between the cations and the anions in the extracellular space that is routinely calculated in the laboratory (i.e., AG = [sodium + potassium] – [chloride + bicarbonate]). In some laboratories, the potassium is not measured because the level of potassium in acid-base abnormalities varies. The normal value of the AG is adjusted downward if potassium is eliminated from the equation. The AG, although not real physiologically, is created by the small amounts of anions in the blood (e.g., lactate, phosphates, sulfates, organic anions, and proteins) that are not measured.
This calculation is most often helpful in identifying the cause of metabolic acidosis. As such acids as lactic acid or ketoacids accumulate in the bloodstream, bicarbonate neutralizes them to maintain a normal pH within the blood. Mathematically, when bicarbonate decreases, the AG increases. In general, most metabolic acidotic states (excluding some types of renal tubular acidosis) are associated with an increased AG. The higher the gap is above normal, the more likely that the metabolic acidotic state is associated with the AG. Proteins can have a significant effect on AG. As albumin (usually negatively charged) increases, AG will increase.
A decreased AG is very rare but can occur when there is an increase in unmeasured (calcium or magnesium) cations. A reduction in anionic proteins (nephrotic syndrome) will also decrease AG. For example, a 1 g/dL drop in serum protein is associated with a 2.5 mEq/L drop in AG. Because the anion proteins are lost, the HCO3 increases to maintain electrical neutrality. An increase in cationic proteins (some immunoglobulins) will also decrease AG. Except for hypoproteinemia, conditions that cause a reduced or negative AG are relatively rare compared with those associated with an elevated AG.
Interfering factors
• Hyperlipidemia may cause undermeasurement of sodium and falsely decrease AG.
• Normal values of AG vary according to different normal values for electrolytes, depending on laboratory methods of measurement.
* Drugs that increase AG are many. Examples include carbonic anhydrase inhibitors (e.g., acetazolamide), ethanol, methanol, and salicylate.
* Drugs that decrease AG are also many. Examples include acetazolamide, lithium, spironolactone, and sulindac.
Procedure and patient care
• See inside front cover for Routine Blood Testing.
• Fasting: no
• Blood tube commonly used: red or green
• If the patient is receiving an IV infusion, obtain the blood from the opposite arm.
• The sodium, potassium, chloride, and bicarbonate levels are determined by an automated multichannel analyzer. The AG is then calculated as indicated in the test explanation section.
Abnormal findings
Increased levels
- Lactic acidosis
- Diabetic ketoacidosis
- Alcoholic ketoacidosis
- Starvation
- Renal failure
- Renal tubular acidosis
- Increased gastrointestinal losses of bicarbonate (e.g., diarrhea or fistulae)
- Hypoaldosteronism
Decreased levels
- Excess alkali ingestion
- Multiple myeloma
- Chronic vomiting or gastric suction
- Hyperaldosteronism
- Hypoproteinemia
- Lithium toxicity
- Bromide (cough syrup) toxicity
