What are the causes of high anion gap metabolic acidosis?

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From the Guidelines

High anion gap metabolic alkalosis is typically caused by the simultaneous presence of a high anion gap metabolic acidosis and a primary metabolic alkalosis, with common causes including severe vomiting, nasogastric suction, ketoacidosis, lactic acidosis, or renal failure, as well as the administration of sodium salts of organic acids or certain medications like diuretics. This condition is an uncommon clinical scenario, as high anion gap typically accompanies metabolic acidosis. When it does occur, it is crucial to identify the underlying causes of both the high anion gap acidosis and the metabolic alkalosis.

Possible Causes

  • Severe vomiting or nasogastric suction, which can cause loss of hydrochloric acid and metabolic alkalosis, in a patient with ketoacidosis, lactic acidosis, or renal failure, which can cause high anion gap acidosis 1
  • Administration of sodium salts of organic acids like lactate, citrate, or acetate, found in total parenteral nutrition or massive blood transfusions, which can be metabolized to bicarbonate, causing alkalosis, while contributing to the anion gap
  • Severe hypoalbuminemia, which can artificially elevate the anion gap while a concurrent metabolic alkalosis exists
  • Certain medications like diuretics, which can cause both volume contraction alkalosis and lactic acidosis

Key Considerations

  • Distinguishing between different 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 1
  • Measuring blood lactate, serum salicylate, and blood methanol level to help diagnose certain intoxications
  • Identifying the presence of calcium oxalate and hippurate crystals in the urine to suggest ethylene glycol ingestion
  • Recognizing the characteristic strong odor on the breath associated with paraldehyde ingestion

Treatment Approach

  • Addressing both underlying disorders simultaneously, focusing on correcting volume status, electrolyte abnormalities, and the primary cause of each acid-base disturbance
  • Providing individualized treatment based on the specific causes of the high anion gap metabolic alkalosis, such as correcting ketoacidosis, lactic acidosis, or renal failure, and managing medication-related side effects.

From the Research

Causes of High Anion Gap Metabolic Alkalosis

There are no direct causes of high anion gap metabolic alkalosis mentioned in the provided studies. However, the studies discuss the causes of high anion gap metabolic acidosis, which can be related to the understanding of acid-base disorders.

Related Causes of High Anion Gap Metabolic Acidosis

  • Methanol poisoning 2, 3, 4, 5
  • Ethylene glycol poisoning 2, 3, 4, 5
  • Lactic acidosis 4, 5
  • Diabetic ketoacidosis 4
  • Alcoholic ketoacidosis 4
  • Acute kidney injury 4
  • Chronic kidney disease 4
  • Salicylate poisoning 6, 5
  • Benzoic acid toxicity 6

Diagnostic Approaches

  • Calculating the serum anion gap to determine coexisting acid-base processes 2, 5
  • Comparing the anion gap and osmolar gap to narrow the differential diagnosis 2, 4
  • Measuring plasma osmolality and osmolal gap to guide clinical decision making 4, 5
  • Using mnemonics such as MUDPILES and GOLD MARK to remember causes of high anion gap metabolic acidosis 6, 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Anion-gap metabolic acidemia: case-based analyses.

European journal of clinical nutrition, 2020

Research

Ethylene glycol poisoning with a normal anion gap caused by concurrent ethanol ingestion: importance of the osmolal gap.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 1996

Research

Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2011

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

Unidentified anion gap metabolic acidosis.

Clinical biochemistry, 2019

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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