Anion gap is defined as the difference between measured serum cations and anions. It is calculated by adding the number of chloride and bicarbonate anions together and then subtracting them from the number of sodium and potassium cations in the blood. In other words: (Na+ + K+) - (Cl- + HCO3-) where Na- is sodium, K+ is potassium, Cl- is chloride, and HCO3- is bicarbonate.
The anion gap can be normal, high, or low. The normal level of anion gap is between 8 and 12 milliequivalents per liter of blood. An elevated anion gap reflects an increase in "unmeasured" anions--usually organic acids--that are not normally included in standard determinations of other anions, such as chloride and bicarbonate. The gap is increased when K+, Ca++, or Mg++ is decreased, when the concentration of plasma proteins is increased, or when organic anions such as lactate or foreign anions accumulate in blood. The anion gap is decreased when cations are increased or when plasma albumin is decreased.
A high anion gap indicates metabolic acidosis. If the anion gap level is 20 or above, this signals a problem. A low anion gap is rare but may occur with multiple myeloma, hypoalbuminemia, hyponatremia, or hypomagnesemia.
The anion gap can be used to distinguish probable cause of metabolic acidosis (high anion gap versus normal anion gap metabolic acidosis), which will aid the provider in determining a diagnosis and suitable treatment. Albumin is the major unmeasured anion and contributes almost the whole of the value of the anion gap. An actual high anion gap acidosis in a patient with hypoalbuminaemia may appear as a normal anion gap acidosis.
Metabolic acidosis with increased
anion gap may be caused by an accumulation of organic acids, such as lactic acidosis, ketoacidosis, toxic ingestions (ethylene glycol, salicylates, methanol, paraldehyde), and acute renal failure. This may also occur because of reduced inorganic acid excretion, such as that seen in chronic renal failure. Metabolic acidosis accompanied by normal
anion gap may be caused by GI bicarb loss (diarrhea, ileostomy, colostomy), renal tubular acidosis, interstitial renal disease, ureterosigmoid loop, ureteroileal conduit, and ingestion of acetazolamide or ammonium chloride.
Diabetic ketoacidosis is a serum glucose level greater than 300 mg per dL, ketones in the serum, and a pH less than 7.3 Serum sodium is often low secondary to elevated serum glucose. Serum potassium is often elevated secondary to the acidosis. Diabetic ketoacidosis is treated with insulin, fluids and correction of the electrolyte disturbances.