What are the causes of anion gap metabolic acidosis?

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From the Guidelines

Anion gap metabolic acidosis is primarily caused by the accumulation of acid in the body, with the most common causes including diabetic ketoacidosis, lactic acidosis, and ingestion of substances such as methanol, ethylene glycol, and salicylates, as well as chronic renal failure. The pathophysiology of anion gap metabolic acidosis involves either increased acid production, decreased acid excretion, or ingestion of substances that metabolize to acids. According to the study by 1, DKA must also be distinguished from other causes of high-anion gap metabolic acidosis, including lactic acidosis, ingestion of drugs such as salicylate, methanol, ethylene glycol, and paraldehyde, and chronic renal failure.

Common Causes

  • Diabetic ketoacidosis (DKA)
  • Lactic acidosis
  • Methanol ingestion
  • Ethylene glycol ingestion
  • Salicylate (aspirin) overdose
  • Chronic renal failure

Diagnosis and Treatment

The diagnosis of anion gap metabolic acidosis involves measuring the anion gap, which is calculated as (Na+) - (Cl + HCO3) (mEq/l) 1. Treatment depends on identifying and addressing the underlying cause, while supporting the patient with intravenous fluids and sometimes bicarbonate therapy for severe cases. Prompt recognition is essential as some causes like methanol or ethylene glycol poisoning require specific antidotes (fomepizole or ethanol) and potentially hemodialysis to prevent serious complications including organ damage and death, as highlighted in the study by 1.

Recent Recommendations

The study by 1 emphasizes the importance of measuring glycolate concentration in cases of suspected ethylene glycol poisoning, as it correlates with acute kidney injury and death. Hemodialysis is recommended in cases of severe ethylene glycol poisoning, especially when the glycolate concentration exceeds 12 mmol/L. However, the use of fomepizole may lower glycolate concentrations faster than hemodialysis, although this requires further caution and consideration of the specific clinical context.

From the Research

Causes of Anion Gap Metabolic Acidosis

  • Lactic acidosis, which can be caused by decreased oxygen delivery or defective oxygen utilization 2, 3
  • Ketoacidosis, usually secondary to diabetes or alcohol 2, 3
  • Toxin or drug-induced acidosis, such as methanol, ethylene glycol, and salicylates 2, 3
  • Uremia, which is associated with a mild acidosis secondary to decreased ammonia secretion and an anion gap caused by the retention of unmeasured anions 2
  • Intoxication with other substances, such as pyroglutamic acid (5-oxoproline), propylene glycol, or djenkol bean (gjenkolism) 3
  • Renal failure 3, 4

Diagnosis and Calculation

  • The anion gap is calculated as [Na+] - ([Cl-] + [HCO3-]) = Unmeasured anions - Unmeasured cations 5
  • A normal anion gap is mostly due to negatively charged albumin, with a normal range of 8-12 meq/l 5
  • Calculating the serum anion gap allows determination of coexisting acid-base processes in a patient 5
  • Comparing the anion gap and osmolar gap can narrow the differential diagnosis to include toxic alcohol ingestions with acidic metabolites such as ethylene glycol and methanol 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Anion gap acidosis.

Seminars in nephrology, 1998

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

Anion-gap metabolic acidemia: case-based analyses.

European journal of clinical nutrition, 2020

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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