What are the causes of high anion gap (anion gap) metabolic acidosis?

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From the Guidelines

To test for high anion gap metabolic acidosis, obtain arterial blood gas and serum electrolytes including sodium, potassium, chloride, and bicarbonate, and calculate the anion gap using the formula: Anion Gap = Na⁺ - (Cl⁻ + HCO₃⁻), with normal values between 8-12 mEq/L, as this is crucial for promptly identifying and managing life-threatening conditions 1.

Key Steps in Testing

  • Obtain arterial blood gas to assess the severity of acidosis
  • Measure serum electrolytes, including sodium, potassium, chloride, and bicarbonate, to calculate the anion gap
  • Calculate the anion gap using the formula: Anion Gap = Na⁺ - (Cl⁻ + HCO₃⁻)
  • Additional testing should include:
    • Serum lactate to evaluate for lactic acidosis
    • Ketones and glucose to assess for diabetic ketoacidosis (DKA) 1
    • Renal function tests (BUN, creatinine) to evaluate for renal failure
    • Toxicology screening to identify potential ingestions
    • Serum osmolality to calculate the osmolal gap, which is useful for diagnosing toxic alcohol ingestion

Identifying Common Causes

The mnemonic MUDPILES can help identify common causes of high anion gap metabolic acidosis:

  • Methanol
  • Uremia
  • Diabetic ketoacidosis
  • Propylene glycol
  • Isoniazid/Iron
  • Lactic acidosis
  • Ethylene glycol
  • Salicylates Specific tests for these conditions include serum ketones and glucose for DKA, lactate for lactic acidosis, and toxicology screens for ingestions 1.

Importance of Prompt Testing

Testing should be performed promptly, as metabolic acidosis can rapidly deteriorate into life-threatening conditions requiring immediate intervention. The delta gap (change in anion gap divided by change in bicarbonate) can help determine if mixed acid-base disorders are present, guiding further management and treatment.

From the Research

Testing High Anion Gap Metabolic Acidosis

  • High anion gap metabolic acidosis can be caused by various factors, including lactic acidosis, ketoacidosis, renal failure, and intoxication with certain substances 2.
  • The diagnosis of high anion gap metabolic acidosis is often established through a combination of clinical evaluation, laboratory tests, and calculation of the anion gap 3.
  • The anion gap is a mathematical construct that compares the blood sodium concentration with the sum of the chloride and bicarbonate concentrations, and it can help identify the underlying cause of metabolic acidosis 3.
  • In patients with lactic acidosis, the Δ anion gap/Δ bicarbonate ratio can be used to detect coexisting acid-base disorders, and this ratio may be higher than traditionally thought in the early stages of lactic acidosis 4.
  • Treatment of high anion gap metabolic acidosis depends on the underlying cause, and sodium bicarbonate administration may be considered in some cases, but its use is controversial and may be associated with higher mortality in certain situations 5, 2.

Key Considerations

  • The cause of high anion gap metabolic acidosis should be identified as quickly as possible to guide treatment 6.
  • Calculation of the anion gap and Δ anion gap/Δ bicarbonate ratio can provide valuable information for diagnosis and management 3, 4.
  • Sodium bicarbonate administration should be used with caution in patients with lactic acidosis, as it may not improve outcomes and may even be harmful 5, 2.
  • Treatment of the underlying cause of high anion gap metabolic acidosis is crucial, and may involve addressing issues such as tissue oxygenation, renal function, and electrolyte imbalances 2, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Metabolic acidosis.

Acta medica Indonesiana, 2007

Research

Approach to Patients With High Anion Gap Metabolic Acidosis: Core Curriculum 2021.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2021

Research

Review of Clinical Disorders Causing Metabolic Acidosis.

Advances in chronic kidney disease, 2022

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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