High Anion Gap Metabolic Acidosis - HAGMA

Simply put, High Anion Gap Metabolic Acidosis (HAGMA) is a type of metabolic acidosis caused by a high anion gap usually situated above 12 mEq/L. Metabolic acidosis can be categorized as either high or normal anion gap based on the presence or absence of unmeasured anions in serum. In general, it is caused by an accumulation of acid components within serum. Usually due to;

• Increased acid production or acid indigestion
• Decreased acid excretion
• GI or renal HCO3- loss

With the help of this formula, we can better understand the relationship between the anions and the cations which are responsible for the calculation of the gap itself 

AG = ([Na?] - [K+]) - ([Cl¯] - [HCO3¯])

In general, the balance between the anions (negative ions) and the cations(positive ions) is kept neutral. In other words, the electrical charge between the anions and cations are in equilibrium. In daily practice, potassium (K+) is often left out during the calculation due to the very low concentrations of it. Therefore the most used equation is;

AG = [Na?] - ([Cl¯] - [HCO3¯])

Keep in mind that the gap is calculated according to how many ions are not accounted for by the lab measurements (seen in the above equation). A normal serum anion gap is usually kept anywhere between 6 - 12 mEq/L however due to some amount of unmeasurable anions (margin of error) anything lower than 11 mEq/L is considered normal. A healthy subject should present, with an anion gap of 0 to slightly normal of <10 mEq/L.

Why is it Useful?

Anion gap is commonly performed for patients that present with altered mental status, unknown exposure, acute renal failure and acute illnesses. It helps provide a possible differential diagnosis in certain situations. The most common causes of HAGMA related to the accumulation of acid are;

• Ketoacidosis
• Lactic acidosis
• Renal Failure
• Toxic ingestions

Other causes are responsible for normal anion gap acidosis which is typically related directly to the kidneys.

Identifying causes of HAGMA

If ever you are attending a patient that present with a high anion gap metabolic acidosis here is a mnemonic I like to use:

GOLDMARK

G - Glycols (ethylene and propylene glycol)

O - Oxoproline (paracetamol metabolite)

L - L-lactate 

D - D-lactate

M - Methanol

A - Aspirin (and other salicylates) 

R - Renal failure (including uremia)

K - Ketoacidosis

There are multiple alternatives such as MUDPLIES and KARMEL which are also easy to remember. It all up to personal preferences although I believe GOLDMARK covers all important possible causes of HAGMA which was proposed by The Lancet. GOLDMARK is also the most recent and clinically relevant mnemonic to date. 

MUDPILES

M - Methanol

U - Uremia 

D - Diabetic ketoacidosis

P - Paracetamol, propylene glycol

I - Infection, Iron, Isoniazid, Inborn errors of metabolism

L - Lactic acid

E - Ethylene glycol

S - Salicylates 

KARMEL

K - Ketoacidosis

A - Aspirin

R - Renal failure

M - Methanol

E - Ethylene glycol

L - Lactic acidosis