Anion Gap
The anion gap is a calculation from sodium, chloride and bicarbonate that helps clinicians look into the acid-base balance of your blood.
AI-verified against cited sources. Awaiting expert reviewAlso called AG, AnGAPLOINC 33037-3
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What it is
The anion gap is not measured directly. Your lab calculates it from three electrolytes on a routine panel: sodium minus the sum of chloride and bicarbonate. The result stands for the negatively charged particles in your blood that the panel does not measure, such as albumin, phosphate and organic acids. When acids build up, the gap usually widens. The usual range depends on the lab's instruments, so the range on your own report matters most.
Why it matters
A higher-than-usual gap most often points toward a build-up of acid in the blood (metabolic acidosis), for example from poorly controlled diabetes, kidney problems or certain poisons. A lower-than-usual gap most often reflects a low albumin level or a lab error. The number is only a clue. Normal ranges are wide, so a meaningful rise can still sit inside your lab's range. It is read together with bicarbonate, albumin, kidney function, glucose and your symptoms.
If it’s low
A result below your lab's range is called a low anion gap. It is uncommon. The most common cause is a low albumin level, because albumin accounts for many of the unmeasured negative charges. A lab error is another common reason, so the test is often repeated. Rarely, an unusual protein in the blood or intoxication with lithium, bromide or iodide can lower it. Your clinician can put your result in context.
Common causes
- Low albumin, which can come from not eating enough protein, kidney problems, liver disease, heart disease or some cancers
- A lab error, such as a measurement problem with sodium, chloride or bicarbonate
- An unusual protein in the blood (paraproteinemia), as in multiple myeloma
- Intoxication with lithium, bromide or iodide (rare)
What can help
- Ask your clinician whether albumin and other protein tests should be checked or repeated
- Ask whether any of your medicines, including lithium, could be involved
If it’s high
A result above your lab's range is called a high anion gap. It most often means extra acid is building up in the blood. Common reasons include ketones from poorly controlled diabetes, lactic acid, kidney failure and poisoning with substances such as aspirin (salicylate), methanol or ethylene glycol (antifreeze). A high gap can also come from a lab error, a very high phosphate level or an unusual protein in the blood. Mild changes can have simple explanations. Your clinician can put your result in context, and a clearly high gap with symptoms needs prompt attention.
Common causes
- Dehydration
- A lab error
- Lactic acid build-up (lactic acidosis), including after very hard exercise
- Ketoacidosis from poorly controlled diabetes
- Kidney failure
- A very high phosphate level, an unusual protein in the blood (paraprotein) or metabolic alkalosis
- Poisoning or overdose, such as with aspirin (salicylate), methanol or ethylene glycol (antifreeze)
What can help
- Ask your clinician whether bicarbonate, glucose, kidney function, lactate or a blood gas should be checked or repeated
- Tell your clinician about every medicine and supplement you take, including aspirin
Usual ranges
What labs print as the reference range, by who was tested. Ranges differ a little between labs, so the range on your own report is the one your result is judged against.
For adults: 7–15 mmol/L. Source: Mayo Clinic Laboratories (catalog copy hosted by Schneck Medical Center), ARUP Laboratories, Clinical Journal of the American Society of Nephrology, Merck Manual Professional Version, MedlinePlus (US National Library of Medicine).
What can affect your result
- Albumin: a low level lowers the gap and can hide a real increase
- Method: the normal value varies with the methods used to measure sodium, chloride and bicarbonate, and between people
- Formula: some labs, especially outside the US, add potassium, which raises the result by about your potassium level (3.6–5.2 mmol/L is the usual range at Mayo Clinic Laboratories)
- Phosphate and unusual proteins (paraproteins)
- Age: Mayo Clinic Laboratories has not established an interval for children under 7
- Lab error in any of the three electrolytes
- A measurement error in sodium, chloride or bicarbonate carries straight into the anion gap. Samples with damaged red cells (hemolysis) are rejected by Mayo Clinic Laboratories.
- Low albumin lowers the gap and can hide a real increase. Each 1 g/dL (10 g/L) drop in albumin lowers it by about 2.5 mmol/L (Figge 1998).
- Very high phosphate, unusual proteins in the blood (paraproteins) and some intoxications can raise or lower the gap (Kraut and Madias 2007).
- Serum should be separated from the cells within 2 hours (Mayo Clinic Laboratories).
Hours to days, as acid-base balance and the underlying cause change.
When to talk to a clinician
Contact the clinician who ordered the test soon if your anion gap is outside your lab's range, especially with nausea or vomiting, fast breathing, unusual tiredness, confusion or a fast heartbeat. Call 911 or your local emergency number for trouble breathing, confusion, fainting, or if you may have swallowed antifreeze, methanol or too much aspirin. No published critical value was found for the anion gap itself.
Questions you could ask
- Does my lab include potassium in its anion gap?
- How often should it be rechecked?
- Which of my other results, such as bicarbonate, glucose or kidney function, fit with a higher gap?
- Should we check lactate, ketones or a blood gas?
- Could a low albumin explain a lower gap?
- Should we repeat the test?
Questions people ask
Is a high anion gap always serious?
Not always. Small changes can reflect lab differences, hydration or a short-term cause. A clearly high gap, especially with a low bicarbonate or symptoms, is a reason for your clinician to look for a cause.
Why is my anion gap low?
The most common reason is a low albumin level. Lab errors also happen, so clinicians often repeat the test.
Why is the range on my report different from ranges I see online?
Labs measure sodium, chloride and bicarbonate with different instruments, and some also add potassium to the formula. The result and the range move together, so use the range on your own report.
Show the science and sources
Units
- 1 mmol/L = 1 mmol/L
- 1 mmol/L = 1 mEq/L
Is a change real?
Anion Gap naturally varies about 9.5% from test to test in the same healthy person. Between two results from the same lab, a change of roughly 29% or more is unlikely to be day-to-day noise or lab variation (95% reference change value). Source: Desirable Biological Variation Database specifications, 2014 update (Minchinela J, Ricos C, et al.; the 'Ricos database', a compilation of median published CVI/CVG).
For clinicians and researchers
The serum anion gap is defined as sodium minus the sum of chloride and bicarbonate (Kraut and Madias 2007). Some labs add potassium. LOINC has separate 'Calculated.3Ions' (10466-1) and 'Calculated.4Ions' (1863-0) codes; only the three-ion version is covered here, and 1863-0 is left out because the four-ion version is understood to add potassium and run higher. Mayo Clinic Laboratories prints 7–15 for ages 7 and older. Kraut and Nagami (2013) note that the normal range is wide (often 8–10 mEq/L across; their Table 2 lists healthy-population ranges from 5–12 to 10–20 mEq/L by analyzer), so an increase in unmeasured anions can be present without the gap exceeding the upper limit, and they suggest an individual baseline. Normal values vary with the methods used to measure the three electrolytes and between individuals. Low values most commonly reflect lab error or hypoalbuminemia, and less often paraproteinemia or lithium, bromide or iodide intoxication; high values most commonly reflect metabolic acidosis but also lab error, metabolic alkalosis, hyperphosphatemia or paraproteinemia (Kraut and Madias 2007). Figge and colleagues (1998) derived an albumin adjustment: adjusted anion gap = observed gap + 0.25 × (normal albumin − observed albumin in g/L), or a factor of 2.5 when albumin is in g/dL. The Merck Manual classifies metabolic acidosis into high and normal anion gap types, with ketones, lactate, kidney failure and drugs or toxins as the high-gap causes, and notes that an osmolal gap can point toward methanol or ethylene glycol; a delta gap is calculated to look for a second acid-base disorder. The urinary anion gap is a separate test.
LOINC 33037-3 (primary), 10466-1. Specimen: calculated.
Sources
- Electrolyte Panel, Serum (test ID ELPSR), Mayo Clinic Laboratories (catalog copy hosted by Schneck Medical Center)
- Basic Metabolic Panel, Serum (test ID BMAMA), Mayo Clinic Laboratories (catalog copy hosted by Schneck Medical Center)
- Basic Metabolic Panel (test 0020399), ARUP Laboratories
- Serum anion gap: its uses and limitations in clinical medicine, Clinical Journal of the American Society of Nephrology (2007)
- The serum anion gap in the evaluation of acid-base disorders: what are its limitations and can its effectiveness be improved?, Clinical Journal of the American Society of Nephrology (2013)
- Anion gap and hypoalbuminemia, Critical Care Medicine (1998)
- Acid-Base Disorders, Merck Manual Professional Version
- Metabolic Acidosis, Merck Manual Professional Version (2025)
- Anion Gap Blood Test, MedlinePlus (US National Library of Medicine)
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