What causes high anion gap metabolic alkalosis?

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From the Guidelines

High anion gap metabolic alkalosis is a contradictory term, but it can occur as a mixed acid-base disorder where primary metabolic alkalosis coexists with high anion gap metabolic acidosis, and the most common causes include toxic ingestions, such as ethylene glycol poisoning, as seen in the study by 1. The term "high anion gap metabolic alkalosis" seems contradictory because metabolic alkalosis is characterized by elevated bicarbonate levels and increased blood pH, whereas a high anion gap typically indicates metabolic acidosis. However, in clinical practice, it's possible for a mixed acid-base disorder to occur, where a primary metabolic alkalosis coexists with a high anion gap metabolic acidosis. Common causes of metabolic alkalosis include:

  • Vomiting
  • Nasogastric suction
  • Diuretic use, especially loop and thiazide diuretics
  • Excessive alkali administration On the other hand, high anion gap metabolic acidosis results from conditions like:
  • Diabetic ketoacidosis
  • Lactic acidosis
  • Kidney failure
  • Toxic ingestions, such as methanol, ethylene glycol, or salicylates
  • Starvation When these conditions occur simultaneously, the alkalosis may partially or completely mask the acidosis, making diagnosis challenging. Laboratory findings would show an elevated bicarbonate level from the alkalosis, but also an increased anion gap from the acidosis, as observed in the study by 1, which reported an anion gap of 32 25, 39 mmol/L in patients with ethylene glycol poisoning. Treatment must address both underlying conditions, focusing first on the most life-threatening component while providing supportive care, including fluid resuscitation, electrolyte replacement, and specific interventions for the causative conditions, such as extracorporeal treatment for ethylene glycol poisoning, as recommended by 1.

From the Research

Causes of High Anion Gap Metabolic Alkalosis

  • Metabolic alkalosis can be caused by various factors, including surreptitious ingestion of substances with mineralocorticoid activity, abuse of laxatives or diuretics, and long-term use of alkalis 2.
  • In some cases, the cause of metabolic alkalosis may be difficult to identify, especially when patients engage in clandestine behaviors such as surreptitious vomiting or use of drugs and herbal supplements with mineralocorticoid activity 2.
  • The use of urine pH and anion gap can be helpful in the differential diagnosis of metabolic alkalosis, particularly in cases where the patient's history is incomplete or misleading 2.

Relationship to Anion Gap Metabolic Acidosis

  • While the provided studies primarily discuss anion gap metabolic acidosis, it is essential to note that the mechanisms and causes of anion gap metabolic acidosis can be distinct from those of metabolic alkalosis.
  • Certain conditions, such as 5-oxoprolinemia (pyroglutamic aciduria), can cause high anion gap metabolic acidosis, particularly in patients with renal dysfunction, sepsis, or those receiving certain medications like acetaminophen 3, 4, 5.
  • However, these conditions are not directly related to high anion gap metabolic alkalosis.

Limitations of Available Evidence

  • The provided studies do not directly address the causes of high anion gap metabolic alkalosis.
  • Further research is needed to fully understand the mechanisms and causes of high anion gap metabolic alkalosis.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Metabolic alkalosis from unsuspected ingestion: use of urine pH and anion gap.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2012

Research

Acetaminophen-induced anion gap metabolic acidosis and 5-oxoprolinuria (pyroglutamic aciduria) acquired in hospital.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2005

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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