What is the clinical significance of an anion gap of 5?

Clinical Significance of Anion Gap of 5

An anion gap of 5 mmol/L is at the lower end of normal and has minimal clinical significance in most cases, but warrants investigation for hypoalbuminemia, hyperglobulinemia (particularly IgG multiple myeloma), or laboratory error. 1

Understanding the Normal Range

• The modern reference range for anion gap using ion-selective electrode methodology is 3-11 mmol/L or 5-12 mmol/L, significantly lower than the outdated range of 8-16 mmol/L that many clinicians still mistakenly reference. 1
• An anion gap of 5 mmol/L falls within the normal range and does not indicate metabolic acidosis or other acid-base disturbance. 1
• The anion gap should be calculated using the formula: Na+ + K+ - Cl- - HCO3- (though many laboratories use Na+ - Cl- - HCO3-). 2, 3

Clinical Scenarios to Consider with Low-Normal Anion Gap

Hypoalbuminemia

• Each 1 g/dL decrease in serum albumin lowers the anion gap by approximately 2.5-3 mEq/L, meaning a low-normal anion gap of 5 may actually mask an elevated anion gap acidosis in patients with low albumin. 4
• Always correct the anion gap for albumin level to avoid missing occult metabolic acidosis. 4

Hyperglobulinemia

• IgG multiple myeloma can present with anion gaps as low as 2 mmol/L due to the cationic nature of the paraprotein. 1
• If the anion gap is 5 mmol/L or lower, consider checking serum protein electrophoresis to rule out paraproteinemia. 1

Laboratory Quality Control

• Anion gaps below 2 mmol/L are rare and should prompt verification of electrolyte measurements for laboratory error. 1
• An anion gap of 5 mmol/L, while within normal range, may warrant repeat measurement if clinical suspicion exists for electrolyte abnormalities. 1

When Low Anion Gap Has Limited Utility

• Decreased anion gap has little clinical utility compared to elevated anion gap, as it can result from numerous mechanisms and rarely points to a specific diagnosis. 5
• The most common causes of truly decreased anion gap (below the reference range) include liver cirrhosis and nephrotic syndrome, though an anion gap of 5 is not technically decreased. 1

Key Clinical Pitfall

• Do not use the outdated reference range of 8-16 mmol/L, as this leads to misinterpretation and unnecessary workup for "low" anion gaps that are actually normal by modern standards. 1
• The wide range of normal values (8-10 mEq/L variation) means that individual baseline values vary considerably, and a single measurement of 5 mmol/L without clinical context has limited significance. 6

Practical Approach

• Check serum albumin level and correct the anion gap accordingly. 4
• If corrected anion gap remains low-normal and patient has no symptoms, no further workup is needed. 1
• If clinical suspicion exists for paraproteinemia (unexplained anemia, bone pain, renal dysfunction), obtain serum protein electrophoresis. 1
• Verify that arterial blood gas shows normal pH and bicarbonate to confirm absence of acid-base disturbance. 3