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Instalab ResearchThe anion gap is calculated from electrolytes in your blood using a simple formula: sodium minus (chloride plus bicarbonate). The result represents "unmeasured" charged particles in your blood, things like lactate (from muscle activity or poor oxygen delivery), ketones (from diabetes or starvation), and proteins like albumin.
Your blood always contains both positive charges (called cations, like sodium) and negative charges (called anions, like chloride and bicarbonate). These should balance out. When they don't, the "gap" between measured positives and negatives suggests something else is present that the standard test isn't directly measuring.
A typical reference range falls between 8 and 16 mmol/L, but different labs use different methods, so your "normal" range might differ slightly. Always compare your result to the reference range printed on your specific lab report.
A high anion gap indicates that unmeasured acids have accumulated in your blood. Doctors call this "high anion gap metabolic acidosis," and it narrows down the possible causes considerably. The common culprits include:
When physicians see an elevated anion gap, they typically investigate these possibilities based on your symptoms and medical history. The calculation helps them distinguish between different types of acid-base problems, each requiring different treatments.
A low or even negative anion gap is less common. It usually reflects a lab error, low albumin levels (common in hospitalized or malnourished patients), or rarely, conditions like multiple myeloma where abnormal proteins can skew the measurement.
If your anion gap comes back unusually low, your doctor will likely check your albumin level and possibly repeat the test to confirm the finding.
This is where context matters enormously. Research consistently shows that the anion gap's predictive power comes primarily from studies of very sick patients in emergency rooms and intensive care units.
For critically ill ICU patients, higher anion gap values clearly correlate with worse outcomes. One study of emergency room patients found that those with an anion gap above 16 had 12% mortality within one week, compared to just 0.5% for those with normal values. In sepsis patients, each standard deviation increase in anion gap raised 28-day mortality risk by about 20%. Studies of patients with acute pulmonary edema, cardiogenic shock, cirrhosis, acute pancreatitis, and diabetic kidney disease all found similar patterns: higher gaps predicted worse short-term outcomes.
However, these findings come from people who were already seriously ill. If you're a generally healthy person who happened to get bloodwork and noticed a mildly elevated anion gap (say, 17 or 18), this doesn't carry the same weight. It might simply mean:
A mildly elevated result in an otherwise healthy person warrants a conversation with your doctor and possibly a repeat test, not immediate alarm.
Here's a crucial wrinkle: albumin (a major blood protein) significantly affects the anion gap calculation. Sick patients often have low albumin, and this can mask a truly elevated anion gap, making it look normal when it shouldn't be.
To address this, many ICU studies use an "albumin-corrected anion gap" (ACAG). Research shows this corrected value predicts outcomes more reliably in hospitalized patients. For example, in trauma patients, an ACAG above 20 mmol/L was associated with more than three times the in-hospital mortality risk. In cirrhosis patients, an ACAG above 20 predicted significantly higher mortality at 30 days and even out to one year.
If you're hospitalized and your doctor mentions the anion gap, ask whether they've corrected it for your albumin level. This gives a more accurate picture, especially if you've been sick for a while.
Short answer: no. There's no evidence supporting anion gap testing as a screening tool for healthy people without symptoms. The research base is almost entirely built on hospitalized patients with known serious conditions.
The anion gap comes "for free" when your doctor orders a basic metabolic panel, meaning it's calculated automatically from the electrolytes already being measured. So if you have routine bloodwork that includes electrolytes, the anion gap will appear on your results. But ordering bloodwork just to check your anion gap as a wellness screen has no scientific backing.
If you have kidney disease, diabetes, liver disease, or other chronic conditions, your doctor may pay more attention to anion gap trends over time. But for routine health maintenance in someone who feels well, it's not a number worth seeking out.
Based on the research, here are some practical thresholds to keep in mind:
For healthy outpatients with no symptoms, a mildly elevated result (17 to 18 mmol/L) usually warrants rechecking the lab and ensuring you were well-hydrated. It's not an emergency.
For hospitalized or ICU patients, anion gap values of 16 to 18 or above (or albumin-corrected values of 18 to 20 or above) deserve urgent attention. These levels consistently predicted higher mortality across multiple studies examining sepsis, pancreatitis, respiratory distress, shock, and other critical conditions. In one study of sepsis patients with acute kidney injury, those with anion gaps of 18 or above had 32% mortality, compared to 11% in those with lower values.
For people with chronic conditions like diabetes, kidney disease, or liver disease, discuss with your doctor what anion gap range they consider concerning for your specific situation. Your baseline may differ from the general population.
If you see the anion gap on your lab results, here's what to do:
The anion gap is a useful tool that helps doctors narrow down what's going wrong when something is clearly wrong. But it's not a health score, not a predictor of future problems in healthy people, and not something to lose sleep over if it's mildly abnormal on routine bloodwork. As with most lab values, interpretation requires context, and that's exactly what your doctor is trained to provide.