What are the causes of metabolic acidosis?

Causes of Metabolic Acidosis

Metabolic acidosis can be categorized into high anion gap metabolic acidosis (HAGMA) and normal anion gap (hyperchloremic) metabolic acidosis, with specific causes in each category. 1

Classification by Anion Gap

High Anion Gap Metabolic Acidosis (HAGMA)

• Lactic acidosis

  • Circulatory insufficiency due to shock or severe dehydration 2
  • Tissue hypoxia 3
  • Severe primary lactic acidosis 2
  • Metformin (biguanide) therapy, especially in renal impairment 1

• Ketoacidosis

  • Diabetic ketoacidosis (uncontrolled diabetes) 2, 1
  • Alcoholic ketoacidosis
  • Starvation ketoacidosis

• Renal Failure

  • Severe renal disease 2
  • Uremic acidosis 4

• Toxin-induced

  • Salicylate poisoning 2
  • Methanol poisoning 2
  • Ethylene glycol ingestion 4
  • Propylene glycol 4
  • Pyroglutamic acid (5-oxoproline) 4

• Inborn Errors of Metabolism

  • Organic acidemias (methylmalonic acidemia, propionic acidemia, isovaleric acidemia) 3
  • Primary hyperoxaluria Type 1 3

Normal Anion Gap (Hyperchloremic) Metabolic Acidosis

• Gastrointestinal bicarbonate loss

  • Severe diarrhea 2
  • Intestinal or pancreatic fistulas 4

• Renal tubular acidosis (RTA)

  • Type I (distal) RTA 5
  • Type II (proximal) RTA 5
  • Type IV RTA (hypoaldosteronism) 5

• Medication-induced

  • Drug-induced hyperkalemia 1
  • Carbonic anhydrase inhibitors 5
  • Certain antibiotics 5

• Other causes

  • Administration of acids or acid precursors 4
  • Early renal failure 4
  • Hyperalimentation solutions 5
  • Djenkol bean ingestion (gjenkolism) 4

Clinical Presentation and Diagnosis

• Laboratory findings:

  • pH < 7.35 3
  • Serum bicarbonate < 22 mmol/L 1
  • Compensatory decrease in PaCO₂ 6
  • Anion gap calculation: [Na⁺] - ([Cl⁻] + [HCO₃⁻]) 1
    • Normal: 8-12 mmol/L
    • Elevated: > 12 mmol/L

• Severity classification 1:

  • Mild: Total CO₂ ≥ 19 mmol/L
  • Moderate to severe: Total CO₂ < 19 mmol/L

Management Considerations

• Treatment should focus on addressing the underlying cause 4

• Sodium bicarbonate therapy is indicated for:

  • Severe metabolic acidosis 2
  • Drug intoxications (barbiturates, salicylates, methanol) 2
  • Hemolytic reactions requiring urine alkalinization 2

• For chronic metabolic acidosis (e.g., in CKD):

  • Sodium bicarbonate supplements may slow progression of kidney disease 7
  • Dietary protein restriction may be beneficial in predialysis patients 8

Clinical Pitfalls and Caveats

• Hypoalbuminemia can falsely lower the calculated anion gap; correction may be necessary 1
• Mixed acid-base disorders are common and may complicate diagnosis
• Metabolic acidosis in critically ill patients is associated with increased morbidity and mortality 4
• Protein catabolism increases in metabolic acidosis, leading to muscle wasting and negative nitrogen balance 8
• For organic acidosis (e.g., lactic acidosis), sodium bicarbonate treatment remains controversial and may not reduce morbidity or mortality 4
• Always interpret acid-base disorders in the context of the patient's clinical presentation and other laboratory values 1