The anion gap (AG) is the calculated difference between the sum of the sodium (Na⁺) and potassium (K⁺) ion concentrations (the measured cations) and the sum of the chloride (Cl⁻) and bicarbonate (HCO₃⁻) concentrations (the measured anions). This difference reflects the concentrations of other anions that are present in the extracellular fluid but are not routinely measured, the components of which include phosphates, sulfates, ketone bodies, lactic acid, and proteins. Increased amounts of these unmeasured anions are produced in the acidotic state. The AG can indicate a state of acidosis and is a symptom of conditions such as dehydration, diarrhea, kidney disease, and diabetic ketoacidosis (see Table 14.7).

1. Obtain this measurement by calculating the difference between the measured serum cation concentrations (either with or without K⁺) and the measured serum anion concentrations.

2. Use the following formulas:

or

1. An AG occurs with acidosis that is caused by excess metabolic acids and excess serum chloride levels. If there is no change in sodium content, anions such as phosphates, sulfates, and organic acids increase the AG because they replace bicarbonate.

2. Increased AG is associated with an increase in metabolic acid when there is excessive production of metabolic acids, as in:

   1. Alcoholic ketoacidosis

   2. Diabetic ketoacidosis

   3. Fasting and starvation

   4. Ketogenic diets

   5. Lactic acidosis

   6. Poisoning by salicylate, ethylene glycol (antifreeze), methanol, or propyl alcohol

3. Increased AG is also associated with decreased loss of metabolic acids as in acute kidney injury and kidney disease. In the absence of kidney disease or intoxication with drugs or toxins, an increase in AG is assumed to be caused by ketoacidosis or lactate accumulation.

4. AG includes the determination of three gaps of toxicology (influence of drugs and heavy metals): (1) anion = type A lactic acidosis due to tissue hypoxia, (2) osmolar gap, and (3) oxygen saturation gap.

5. A list of drugs and toxic substances that cause increased AG (>12 mEq/L or >12 mmol/L) include the following:

   • Toxins that cause osmolar gap >10 mOsm from baseline include ethanol, ethylene glycol, glycerol, hypermagnesemia (>9.5 mEq/L or >9.5 mmol/L), isopropanol (acetone), iodine (questionable), mannitol, methanol, and sorbitol.

6. Drugs and toxins that cause decreased AG (<6 mEq/L or <6 mmol/L) include the following: acidosis—acetazolamide, amiloride, ammonium chloride, amphotericin B, bromide, fialuridine, iodide, kombucha tea, lithium, polymyxin B, spironolactone, sulindac, toluene, and tromethamine.

7. Toxins that cause an oxygen saturation gap (>5% difference between measured and calculated value) include carbon monoxide, cyanide (questionable), hydrogen sulfide (possible), methemoglobin, and nitrates.

8. Increased bicarbonate loss with a normal AG is associated with:

   1. Decreased kidney losses, as in:

      1. Renal tubular acidosis

      2. Use of acetazolamide

   2. Increased chloride levels, as in:

      1. Altered chloride reabsorption by the kidney

      2. Parenteral hyperalimentation

      3. Administration of sodium chloride and ammonium chloride

   3. Loss of intestinal secretions, as in:

      1. Diarrhea

      2. Intestinal suction or fistula

      3. Biliary fistula

9. Low AG is associated with:

   1. Multiple myeloma

   2. Hyponatremia caused by viscous serum

   3. Bromide ingestion (hyperchloremia)

10. The AG may provide evidence of a mixed rather than a simple acid–base disturbance.

Pretest Patient Care

1. Explain the purpose and procedure of the test.

2. Follow guidelines in Chapter 1 for safe, effective, informed pretest care.

Normal

• Normal values are 12 ± 4 mEq/L (12 ± 4 mmol/L).

• If potassium concentration is used in the calculation, the normal value is 16 ± 4 mEq/L (16 ± 4 mmol/L).