Question.

All the following statements regarding the anion gap are true EXCEPT which one?

a. It may be calculated by the formula, anion gap (AG) =  ([Na+] + [K+]) − ([Cl] + [HCO3])
b. Normal anion gap is < 2 mEq/L
c. Ketoacidosis is a cause of raised anion gap
d. Hypoalbuminaemia may cause a falsely low anion gap
e. Excess paracetamol and aspirin are both causes of raised anion gap.

Answer.
The correct answer is b. The normal anion gap is less than 12 – 16mEq/L (depending on exact calculation method)
 
Discussion.
The anion gap is the difference between the measured cations (positive ions) and measured anions (negative ions) in the plasma. It is therefore calculated by subtracting the major plasma anions (CLand HCO3) from the major plasma cations (Na+ and K+) such that the anion gap (AG) =   ([Na+] + [K+]) − ([Cl] + [HCO3]).  The normal value of the anion gap calculated by the above formula is less than 16mEq/L (less than 12 mEq/L if the minor contribution of [K+] is excluded from the calculation).

A raised anion gap indicates the presence of unmeasured cations and in an unwell patient with a metabolic acidosis this may aid diagnosis. The most well-known mnemonic for remembering the causes of a high anion gap metabolic acidosis is MUDPILES:

M – methanol
U – uraemia (chronic renal failure)
D – diabetic ketoacidosis (and other causes of ketoacidosis – ethanol, starvation and metformin)
P – propyl alcohol
I – isoniazid, iron
L – lactic acidosis (sepsis, metformin)
E – ethylene glycol
S – salicylates (aspirin)

Other rare causes include cyanide and paracetamol (due to its metabolite, oxoproline).

A low anion gap most frequently arises from hypoalbuminaemia, where the loss of negatively charged albumin protein causes the retention of other anions (Cl and HCO3) to maintain electrical neutrality of plasma. Causes of hypoalbuminaemia include liver cirrhosis, nephrotic syndrome and congestive cardiac failure.