22nd June 2023

Metabolic acidosis and the anion gap

High Anion Gap Metabolic Acidosis (HAGMA)

When the corrected anion gap is greater than 12 mmol/L, it is classed as a high anion gap metabolic acidosis. The increase in the anion gap suggests that there are unmeasured anions causing this difference, a suggestion that can be seen in a number of the differential diagnoses associated with high anion gap metabolic acidosis.

A commonly used acronym to remember the causes of high anion gap metabolic acidosis is CAT MUDPILES:

C = Carbon monoxide, cyanide, congenital
A = Aminoglycosides
T = Theophylline, toluene (glue sniffing)

M = Methanol, metformin
U = Uraemia
D = (Diabetic) Ketoacidosis
P = Paraldehyde, paracetamol, propylene glycol
I = Isoniazid, iron
L = Lactic Acidosis
E = Ethanol/Ethylene Glycol
S = Salicylates

It is worth recalling that ketoacidosis is not only seen in diabetic patients on insulin or, more recently, SLGT2 inhibitors but can also be seen as a result of alcohol excess or starvation.

Management of these patients is based around correcting the underlying cause, i.e., treatment of DKA, consideration of dialysis in the uraemic patient, and antidote for poisoning as appropriate. In some cases, there may be a case for alkalisation with agents such as sodium bicarbonate; however, these decisions should generally be led by someone with experience in the use of sodium bicarbonate and is not appropriate in all cases of HAGMA. Before the commencement of sodium bicarbonate, potassium and calcium levels should be available as these can fall with bicarbonate administration.

Normal Anion Gap Metabolic Acidosis (NAGMA)

If the anion gap is within normal range, it is classed as a normal anion gap metabolic acidosis. It is sometimes also referred to as hyperchloremic metabolic acidosis, as in these patients, the body compensates for the loss of bicarbonate by increasing the reabsorption of chloride.

Compared to HAGMA, the list of differentials for NAGMA is much shorter:

C = Chloride excess
A= Addison’s disease, acetazolamide
G = GI causes – including diarrhoea, vomiting and fistulas (pancreatic, biliary, small bowel, ileostomy)
E = Extras – including renal tubular acidosis, spironolactone, hyperalimentation

Traditionally, the urinary anion gap had been used to delineate if the cause of a normal anion gap metabolic acidosis was from a renal or gastrointestinal source, but recent evidence has suggested this is not reliable due to its lack of correlation to urinary ammonium, and wide range of normal values in healthy individuals.

Like high anion gap metabolic acidosis, the management depends on the underlying aetiology. In the next section, we will cover renal tubular acidosis in more detail, including management where appropriate.