Anion gap

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The anion gap is used to aid in the differential diagnosis of metabolic acidosis.

1 Calculation
2 Uses
3 Normal value ranges
4 Interpretation and causes
5 References
6 External links

[edit] Calculation

It is calculated by subtracting the serum concentrations of chloride and bicarbonate (anions) from the concentrations of sodium plus potassium (cations):

= ( [Na⁺]+[K⁺] )  -  ( [Cl^-]+[HCO₃^-] )

However, for daily practice, the potassium is frequently ignored, leaving the following equation:

= ( [Na⁺] ) - ( [Cl^-]+[HCO₃^-] )

[edit] Uses

The anion gap is representative of the unmeasured anions in the plasma, and these anions are affected differently based on the type of metabolic acidosis. The primary function of the anion gap measurement is to allow a clinician to narrow down the possible causes of a patients metabolic acidosis. For example, if a patient presents with metabolic acidosis, but a normal anion gap, then conditions that cause a high anion gap can be ruled out as being the cause of the acidosis.

[edit] Normal value ranges

In the past, methods for the measurement of the anion gap consisted of colorimetry for [HCO₃^-] and [Cl^-] as well as flame photometry for [Na⁺] and [K⁺]. Thus normal reference values ranged from 8 to 16 mmol/L plasma when not including [K⁺] and from 10 and 20 mmol/L plasma when including [K⁺]. Some specific sources use 15^[1] and 8-16 mEq/L.^[2]^[3]

Modern analysers make use of ion-selective electrodes which give a normal anion gap as <11 mmol/L. Therefore according to the new classification system a high anion gap is anything above 11mmol/L and a normal anion gap is between 3-11 mmol/L.^[4]

[edit] Interpretation and causes

Anion gap can be classified as either high, normal or rare cases low. A high anion gap indicates that there is loss of HCO₃^- without a subsequent increase in Cl^-. Electroneutrality is maintained by the increased production of anions like ketones, lactate, PO₄^-, and SO₄^-; these anions are not part of the anion-gap calculation and therefore a high anion gap results. In patients with a normal anion gap the drop in HCO₃^- is compensated for by an increase in Cl^- and hence is also known as hyperchloremic acidosis.

[edit] High anion gap

Lactic acidosis
Ketoacidosis
Renal failure (Uremia)
Iron
INH
Isopropolol
Ingestions:
- Salicylate
- Ethanol
- Methanol
- Ethylene glycol
- Paraldehyde
- Toluene
- Sulfur
- Cyanide, coupled with elevated venous oxygenation

[edit] Normal anion gap (hyperchloremic acidosis)

Gastrointestinal loss of HCO₃^- (i.e. diarrhea) (note: vomiting causes hypochloraemic alkalosis)
Renal loss of HCO₃^- (i.e. proximal renal tubular acidosis)
Renal dysfunction (i.e. some cases of renal failure, hypoaldosteronism, distal renal tubular acidosis)
Ingestions
- Ammonium chloride
- Hyperalimentation fluids (i.e. total parenteral nutrition)
Some cases of ketoacidosis, particularly during insulin treatment

Alcohol (such as ethanol) can effect anion gap by inducing alcohol dehydrogenase enzyme.

[edit] Low anion gap

A low anion gap is relatively rare but may occur from the presence of abnormal positively charged proteins, as in multiple myeloma, or in the setting of a low serum albumin level.