• AG

• Red, tiger or green top tube
• 3-5 mL of venous blood

Additional information:

• Never collect specimen for this assay above an intravenous line as false results may be seen
• Reject if there is hemolysis

The anion gap is calculated as the sum of the major measured cations minus the sum of the major measured anions:

AG = (Na⁺ + K⁺) - (Cl^- + HCO₃ ^-)

However, potassium is typically excluded from the calculation and the formula used here is:

AG = Na⁺ -(Cl^- + HCO₃ ^-)

The anion gap is useful in:

• Indicating presence of electrolyte imbalance
• Evaluating various types of metabolic acidosis
• Monitoring renal function and total parenteral nutrition

Additional information:

• The normal anion gap indicates presence of unmeasured anions and cations
• Generally, the sum of all the cations is equal to the sum of all the anions in order to have electrochemical balance
• Excess anions are buffered by bicarbonate
• Elevated AG often indicates a state of metabolic acidosis, whether the actual measured venous CO₂ is normal or above normal
• Anion gap metabolic acidosis is often a medical emergency
• This test is not sufficiently sensitive to be used to screen for lactic acidosis (is specific but not sensitive enough)

Consult your laboratory for their normal ranges as these may vary somewhat from the ones listed below.

Notes:

• Normal anion gap does not rule out metabolic acidosis
• Normal anion gap with metabolic acidosis may be seen in:
• Diarrhea
• Renal tubular acidosis
• Hyperalimentation
• Uretero-ileostomy
• Uretero-sigmoidostomy
• External drainage of pancreatico-biliary fluids
• Ammonium chloride and other drugs

Elevated anion gap may be seen in metabolic acidosis. It may occur in the following conditions:

• Renal failure
• Phosphate accumulation
• Sulfate accumulation
• Uremia
• Ketoacidosis
• Diabetic (DKA)
• Alcoholic ketoacidosis
• Starvation
• High protein/ low carbohydrate diet
• Lactic Acidosis
• Others
• Severe dehydration
• Excessive exercise
• Rhabdomyolysis
• Hyperalbuminemia
• Non-ketotic hyperglycemic coma

Drugs and Toxic Agents that cause an elevated anion gap include:

• Aspirin/Salicylate overdose
• Ethylene glycol
• Isoniazid
• Isopropyl alcohol
• Metformin
• Methanol
• Paraldehyde
• Phenformin
• Toluene toxicity

Low anion gap may be seen in the following conditions:

Common causes:

• Hypergammaglobulinemia
• Multiple Myeloma
• Waldenström's macroglobulinemia
• Hyponatremia
• Hypoalbuminemia (1 gm/dl decrease in serum albumin causes a 2.5 mEq/L drop in the AG)
• Cirrhosis
• Nephrosis

Less common causes:

• Hyperchloremia
• Marked hypercalcemia
• Hypermagnesemia
• Hyperkalemia
• Lithium toxicity
• HIV infection
• Hyperlipidemia
• Dilution of extracellular fluids

Drugs that cause decrease in the anion gap include:

• Bromide ingestion (some cough preparations contain dextromethorphan bromide)
• Polymyxin B administration

• Adams BD, Bonzani TA and Hunter CJ. The anion gap does not accurately screen for lactic acidosis in emergency department patients. Emer Med J. 2006;23:179-182.
• Figge J, Jabor A, Kazda A et al. Anion gap and hypoalbuminemia. Crit Care Med.1998;26(11):1807-10.
• Kirschbaum B. Hyperglobulinemia with an increased anion gap. Am J Med Sci 1998; 316(6):393-397.
• Levraut J, Bounatirou T, Ichai C et al. Reliability of anion gap as an indicator of blood lactate in critically ill patients. Intensive Care Med.1997;23(4):417-22.
• Slucher B and Levinson SS. Human immunodeficiency virus infection and anion gap. Annals Clin Lab Sci. 1993; 23(4):249-255.