What are the causes of non-anion gap metabolic acidosis?

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From the Guidelines

Non-anion gap metabolic acidosis is primarily caused by either excessive loss of bicarbonate or excessive retention of chloride, with common causes including gastrointestinal bicarbonate loss, renal bicarbonate wasting, and medication-induced causes. The causes of non-anion gap metabolic acidosis can be multifaceted, involving various mechanisms that lead to an imbalance in the body's acid-base homeostasis. Some of the key causes include:

  • Gastrointestinal bicarbonate loss through conditions such as diarrhea, pancreatic fistulas, or small bowel drainage
  • Renal bicarbonate wasting, which can occur in renal tubular acidosis (RTA), including Type 1 (distal) RTA, Type 2 (proximal) RTA, and Type 4 RTA
  • Medication-induced causes, such as the use of carbonic anhydrase inhibitors like acetazolamide, which increase bicarbonate excretion, and potassium-sparing diuretics such as spironolactone
  • Dilutional acidosis, which can occur with the rapid infusion of chloride-rich fluids like normal saline, as noted in patients recovering from DKA 1
  • Hyperalimentation with amino acid solutions, which can contribute to non-anion gap metabolic acidosis as amino acids are metabolized to strong acids
  • Recovery from ketoacidosis, which may temporarily present as a non-anion gap acidosis as ketones are cleared faster than bicarbonate is regenerated, as seen in the management of diabetic ketoacidosis (DKA) 1 Identifying the specific cause of non-anion gap metabolic acidosis is crucial for appropriate management, which typically involves addressing the underlying condition and sometimes providing bicarbonate supplementation.

From the Research

Causes of Non-Anion Gap Metabolic Acidosis

  • Gastrointestinal bicarbonate loss, such as diarrhea 2, 3
  • Renal tubular acidosis, including distal renal tubular acidosis (dRTA) 4, 3
  • Ileal neobladder urinary diversion for the treatment of bladder cancer 5
  • High-volume ileostomy output causing large bicarbonate losses 6
  • Administration of large quantities of chloride-containing solutions in the treatment of hypovolemia and various shock states 2
  • Chronic laxative abuse, which can mimic dRTA and result in non-anion gap metabolic acidosis 4
  • Drugs-induced hyperkalemia and early renal failure 3
  • Loss of bicarbonate from the kidney or gastrointestinal tract 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Treatment of acute non-anion gap metabolic acidosis.

Clinical kidney journal, 2015

Research

Metabolic acidosis.

Acta medica Indonesiana, 2007

Research

Gut It Out: Laxative Abuse Mimicking Distal Renal Tubular Acidosis.

Kidney & blood pressure research, 2019

Research

Non-Anion Gap Metabolic Acidosis: A Clinical Approach to Evaluation.

American journal of kidney diseases : the official journal of the National Kidney Foundation, 2017

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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