What is the cause of Normal Anion Gap Metabolic Acidosis (NAGMA)?

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Last updated: March 13, 2025View editorial policy

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From the Guidelines

Normal Anion Gap Metabolic Acidosis (NAGMA) is primarily caused by an increase in plasma chloride concentration relative to sodium, which decreases the strong ion difference (SID) and lowers the pH, as explained by the Stewart's approach 1. The pathophysiology of NAGMA is complex, but it can be attributed to various factors, including:

  • Electrolyte imbalances, particularly an increase in chloride ions, which can occur independently of sodium losses 1
  • Renal conservation of chloride, with tubular reabsorption of 60-70% of the filtrated chloride 1
  • Gastrointestinal and skin electrolyte losses, which can be increased under pathological conditions such as bowel obstruction, ileostomy, and peritoneal drainage 1
  • Administration of sodium and chloride-containing solutions, such as normal saline, amino acid, and calcium solutions, during parenteral nutrition 1 Key points to consider in the management of NAGMA include:
  • Monitoring serum electrolytes, particularly sodium, chloride, and potassium, to estimate electrolyte losses and guide replacement therapy 1
  • Avoiding excessive administration of chloride-containing solutions, which can exacerbate the condition 1
  • Considering the use of alternative solutions, such as balanced crystalloids, to minimize chloride intake 1 It is essential to note that the management of NAGMA should be individualized, taking into account the underlying cause and the patient's clinical condition, to minimize morbidity, mortality, and improve quality of life.

From the Research

Causes of Normal Anion Gap Metabolic Acidosis (NAGMA)

  • The cause of NAGMA includes loss of bicarbonate from the gastrointestinal tract or the kidney, also known as hyperchloremic metabolic acidosis 2
  • Gastrointestinal bicarbonate loss is one of the most common causes of hyperchloremic metabolic acidosis 2
  • Renal tubular acidosis (RTA) is essentially characterized by normal anion gap and hyperchloremic metabolic acidosis 3, 4, 5
  • RTA can result from abnormality in bicarbonate ion absorption or hydrogen ion secretion, and can be primary or secondary in nature 3
  • Other causes of NAGMA include renal tubular acidosis, drugs-induced hyperkalemia, early renal failure, and administration of acids 2
  • NAGMA can also be caused by extrarenal manifestations that provide etiologic diagnostic clues, such as changes in renal NH4+, Ca2+, K+, and H2O homeostasis 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Metabolic acidosis.

Acta medica Indonesiana, 2007

Research

Comprehensive clinical approach to renal tubular acidosis.

Clinical and experimental nephrology, 2015

Research

Clinical approach to renal tubular acidosis in adult patients.

International journal of clinical practice, 2011

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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