Anion Gap Explained

The Anion Gap (AG) is a calculated value that represents the difference between the primary measured cations (positively charged ions) and the primary measured anions (negatively charged ions) in the blood serum. It is primarily used to identify the cause of metabolic acidosis.

How is the Anion Gap Calculated?

The formula for calculating the Anion Gap is:

Anion Gap = [Sodium (Na+)] - ([Chloride (Cl-)] + [Bicarbonate (HCO3-)])

All values are typically measured in mEq/L or mmol/L.

Example Calculation

If a patient's lab results are:

• Sodium (Na+): 140 mEq/L
• Chloride (Cl-): 105 mEq/L
• Bicarbonate (HCO3-): 24 mEq/L

The Anion Gap would be calculated as:

AG = 140 - (105 + 24) = 140 - 129 = 11 mEq/L

Interpreting Anion Gap Results

Normal Anion Gap

A normal Anion Gap typically ranges from 8 to 12 mEq/L (some labs use 6-10 mEq/L). A normal AG in the presence of metabolic acidosis suggests a normal anion gap metabolic acidosis (also known as hyperchloremic metabolic acidosis), where the decrease in bicarbonate is compensated by an increase in chloride.

High Anion Gap

A high Anion Gap (typically >12 mEq/L) indicates the presence of unmeasured anions in the blood, which consume bicarbonate. Common causes include:

• Lactic Acidosis: Due to shock, sepsis, or severe hypoxia.
• Ketoacidosis: Diabetic ketoacidosis, alcoholic ketoacidosis, starvation ketoacidosis.
• Renal Failure: Accumulation of sulfates, phosphates, and other organic acids.
• Toxins: Methanol, ethylene glycol, salicylates, paraldehyde.

Low Anion Gap

A low Anion Gap (typically <6 mEq/L) is less common but can be significant. Causes include:

• Hypoalbuminemia: Albumin is a major unmeasured anion; low levels reduce the AG.
• Multiple Myeloma: Due to increased unmeasured cations (e.g., IgG paraprotein).
• Bromide Intoxication: Bromide is an unmeasured anion that can displace chloride.
• Lithium Toxicity: Lithium is an unmeasured cation.

Corrected Anion Gap

Albumin is the most abundant unmeasured anion in the serum. Therefore, changes in serum albumin concentration can affect the Anion Gap. In cases of hypoalbuminemia (low albumin), the Anion Gap may appear falsely normal or low, masking an underlying high anion gap metabolic acidosis.

To account for this, a corrected Anion Gap can be calculated:

Corrected Anion Gap = Measured Anion Gap + (2.5 * (4.0 - Serum Albumin))

Where serum albumin is in g/dL and 4.0 g/dL is considered the average normal albumin level. Each 1 g/dL decrease in albumin below 4.0 g/dL reduces the Anion Gap by approximately 2.5 mEq/L.