The anion gap can be increased due to relatively low levels of cations other than sodium and potassium (e.g. calcium or magnesium).

High anion gap metabolic acidosis is typically caused by acid produced by the body.

The most serious form occurs during various states of shock, due to episodes of decreased liver perfusion.

Various mnemonics are used to assist clinicians in the detection and diagnosis of conditions that may result in high anion gap metabolic acidosis: The newer 2008 mnemonic "GOLD MARK" was proposed in The Lancet reflecting current causes of anion gap metabolic acidosis:[4] The mnemonic MUDPILES is commonly used to remember the causes of increased anion gap metabolic acidosis.

[8] The mnemonic for toxins is ACE GIFTs: Aspirin, Cyanide, Ethanolic ketosis, Glycols (ethylene and propylene), Isoniazid, Ferrous iron, Toluene, salicylates.