What are the causes of anion gap metabolic acidosis?

From the Guidelines

Anion gap metabolic acidosis is primarily caused by conditions such as diabetic ketoacidosis, lactic acidosis, and certain poisonings, including methanol and ethylene glycol, as well as kidney failure, which lead to an accumulation of acids other than bicarbonate in the bloodstream. The causes of anion gap metabolic acidosis can be remembered using the mnemonic "MUDPILES": Methanol, Uremia, Diabetic ketoacidosis, Propylene glycol, Isoniazid/Iron, Lactic acidosis, Ethylene glycol, and Salicylates 1.

Key Causes

• Diabetic ketoacidosis: characterized by hyperglycemia, metabolic acidosis, and increased ketone bodies, often requiring insulin administration and fluid resuscitation for treatment 1.
• Lactic acidosis: typically results from poor tissue perfusion and can be managed by addressing the underlying cause, often with fluids and vasopressors if needed.
• Methanol and ethylene glycol poisoning: specific antidotes like fomepizole may be required, and these conditions can also lead to an osmolar gap in addition to anion gap acidosis 1.
• Kidney failure: can lead to hyperchloremic acidosis but also contributes to anion gap metabolic acidosis due to the accumulation of organic acids.

Diagnosis and Management

Diagnosis involves laboratory testing, including arterial blood gas, electrolytes, and calculation of the anion gap. The anion gap is calculated as (Na+) - (Cl + HCO3) (mEq/l), with values greater than 12 mEq/L typically indicating anion gap metabolic acidosis 1. Management focuses on addressing the underlying cause while supporting the patient, with sodium bicarbonate therapy generally reserved for severe acidosis (pH < 7.1) or when the acidosis itself is causing hemodynamic instability.

Clinical Considerations

Clinical history and physical examination are crucial for identifying the cause of anion gap metabolic acidosis. Specific tests, such as blood lactate, serum salicylate, and blood methanol levels, can help differentiate between causes. The presence of calcium oxalate and hippurate crystals in the urine may suggest ethylene glycol ingestion 1. Prompt identification and appropriate management are critical to improve morbidity, mortality, and quality of life outcomes in patients with anion gap metabolic acidosis, as evidenced by recent studies on the treatment of ethylene glycol poisoning 1.

From the Research

Causes of Anion Gap Metabolic Acidosis

• The causes of high anion gap metabolic acidosis include:
  • Lactic acidosis 2, 3, 4
  • Ketoacidosis 2, 3, 4
  • Renal failure 2, 3
  • Intoxication with ethylene glycol, methanol, salicylate 2, 3, 4
  • Pyroglutamic acid (5-oxoproline) accumulation 5, 2, 6
  • Propylene glycol 2
  • Djenkol bean (gjenkolism) 2
  • Biguanides 4
  • Alcohols 4
  • Polyhydric sugars 4
  • Cyanide and carbon monoxide 4
• These causes can lead to the accumulation of unmeasured organic anions, resulting in an increased anion gap 4
• The diagnosis of high anion gap metabolic acidosis often involves a systematic work-up to identify the underlying cause, including historical and laboratory data 5, 6
• A systematic diagnostic approach is necessary to identify uncommon causes of high anion gap metabolic acidosis, such as 5-oxoproline acidosis (pyroglutamic acidosis) 6