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Anion Gap

The anion gap refers to the concentration of unmeasured anions in blood. It represents anions other than chloride and bicarbonate that are required to electrically balance cations, such as sodium. Unmeasured anions include protein, phosphate, sulfate, and organic acids. The most commonly used formula to measure the gap is:

Sodium - (chloride + bicarbonate) = anion gap

Another way to think of anion gap is:

sodium + unmeasured cations = chloride + bicarbonate + unmeasured anions or

sodium - (chloride + bicarbonate) = unmeasured anions - unmeasured cations

The anion gap is primarily used to classify metabolic acidosis, which is caused by the retention of acid within the body. Hydrogen ion reacts with bicarbonate to form carbon dioxide, which is eliminated by the lungs. As acidosis develops, bicarbonate levels decrease and are replaced by the anionic component of the acid. In inorganic acidosis, the anion is chloride and the anion gap does not change. In organic acidosis, the anion gap increases because bicarbonate decreases, chloride remains constant, and the unmeasured anion (lactate, ketone, phosphate) increases.

Metabolic acidosis can be divided into two categories: normal anion gap and high anion gap.

High anion gap acidosis is caused by acid retention, while normal anion gap acidosis is usually due to loss of bicarbonate.

High Anion Gap

  • Ketoacidosis (diabetes, starvation, ethanol)
  • Lactic acidosis (circulatory or respiratory failure, liver failure, tumors, oral hypoglycemics)
  • Renal failure (uremic acidosis)
  • Poisoning (salicylates, methanol, ethylene glycol)

Normal Anion Gap

  • Drugs (acetazolamide, carbonic anhydrase inhibitor)
  • GI loss of bicarbonate (diarrhea)
  • Ureteroenterostomy (loss of bicarbonate from chloride-bicarbonate exchange)
  • Renal tubular acidosis
  • Excess IV replacement with NaCl

Occasionally, the anion gap may be decreased. The principle causes are hypoalbuminemia, monoclonal gammopathy, excess crystalloid infusion, and lithium intoxication. Albumin is an unmeasured anion, whose concentration can be reduced by decreased synthesis or dilution with IV fluids. A decrease in unmeasured anions decreases the anion gap. Monoclonal proteins, especially IgG, represent unmeasured cations. An increase in unmeasured cations and a decrease in measured cations narrow the anion gap.

Reference range (Vitros Analyzer) is 3 -15 mEq/L.

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