The Anion Gap

And why it's so useful

What is the anion gap?

To help figure out what’s behind a metabolic acidosis we can use a formula to work out the anion gap. There are lots of ions in the plasma, some with a positive charge (H+ for example) which are called cations, and some with a negative charge (Cl- for example) which are called anions. The overall electrical charge of the plasma is neutral, which means the electrical charges of all cations and anions effectively cancel each other out.

An ABG will contain measurements of some cations and anions, but not all. The main cations we measure are sodium (Na+) and potassium (K+), and the main anions are chloride (Cl-) and bicarbonate (HCO3-). Potassium concentrations are generally low, so it doesn’t contribute much to the overall cation-anion relationship and we can ignore it.

Calculating the anion gap

To calculate the anion gap we use the formula

Na+ - ( Cl- + HCO3- )

Some institutions will include potassium: (Na+ + K+) – (Cl- + HCO3-)

This formula will give us the number of unmeasured anions in the plasma. The normal range is approximately 4-12 mmol/L (although this reference range will vary depending on the lab equipment used to measure the ions, another commonly quoted range is 8-16 mmol/L).

What does it tell us?

Unmeasured anions include albumin, phosphate, lactate, and ketone metabolites, among others. If a metabolic acidosis is caused by diseases that increase the number of anions (e.g. lactic acidosis) the anion gap will be increased. This is called a 'high anion gap metabolic acidosis'.

If a metabolic acidosis is due to diseases that cause a drop in bicarbonate (e.g. bicarbonate loss through diarrhoea) we may expect a lower anion gap than normal, but in these cases the kidneys compensate for the loss of bicarbonate ions by reabsorbing more chloride ions. These extra chloride ions are included in our anion gap calculation so we get a 'normal anion gap metabolic acidosis'. (Because of the extra chloride ions this can also be called a hyperchloremic acidosis).

Why is this useful?

By calculating the anion gap we can narrow down the causes of a metabolic acidosis – it tells us if the disease process is causing an increase in unmeasured anions (like lactate) or causing a loss of bicarbonate (like diarrhoea), making diagnosis easier and faster.

Common causes (raised anion gap):

  • Diabetic ketoacidosis
  • Lactic acidosis
  • Drug overdoses (paracetamol, aspirin, alcohol)
  • Poisons (e.g. ethylene glycol)

Common causes (normal anion gap):

  • Diarrhoea
  • Renal tubular acidosis
  • Interstitial nephritis
  • Ammonium chloride poisoning
  • Acetazolamide use