What are the causes of metabolic acidosis?

Causes of Metabolic Acidosis

Metabolic acidosis is caused by failure to excrete acid produced by normal metabolic processes, increased production of acid from abnormal metabolic conditions, or direct loss of bicarbonate from the kidney or gut. 1

Classification of Metabolic Acidosis

Metabolic acidosis can be classified based on the anion gap:

High Anion Gap Metabolic Acidosis

• Lactic acidosis

  • Common cause due to tissue hypoxia from decreased oxygen delivery, low cardiac output, or sepsis 1
  • Metformin-associated lactic acidosis (characterized by blood lactate >5 mmol/L, anion gap acidosis without ketonuria/ketonemia, increased lactate/pyruvate ratio) 2

• Ketoacidosis

  • Diabetic ketoacidosis (DKA) 1
  • Alcoholic ketoacidosis (AKA) 1
  • Starvation ketosis (though serum bicarbonate rarely falls below 18 mEq/L) 1

• Renal failure (acute or chronic) 1, 3

  • Occurs when GFR decreases to less than 20-25% of normal 3

• Toxin ingestion

  • Salicylate, methanol, ethylene glycol, paraldehyde 1
  • Propylene glycol, pyroglutamic acid (5-oxoproline) 4

Normal Anion Gap (Hyperchloremic) Metabolic Acidosis

• Gastrointestinal bicarbonate loss

  • Chronic diarrhea 1, 4
  • Small bowel or pancreatic drainage

• Renal tubular acidosis 4

  • Type 1 (distal)
  • Type 2 (proximal)
  • Type 4 (hyperkalemic)

• Drug-induced hyperkalemia 4

• Early renal failure 4

• Acid administration 4

• Dietary factors

  • Western diet with high animal protein, low fruit/vegetable intake leads to high net endogenous acid production 1

Pathophysiological Mechanisms

1. Increased acid production:

   • Accumulation of organic acids (ketoacids, lactic acid) 5
   • Increased nonvolatile acids from metabolism of sulfur-containing amino acids 1

2. Decreased acid excretion:

   • Renal failure leading to impaired hydrogen ion secretion 3
   • Distal renal tubular acidosis

3. Bicarbonate loss:

   • Direct loss from kidney or gut 1
   • Buffering of excess acid by bicarbonate 1

4. Decreased alkali intake:

   • Low intake of fruits and vegetables (sources of potassium citrate salts) 1

Clinical Characteristics

• Plasma bicarbonate concentrations typically range from 12-22 mEq/L in chronic kidney disease 3
• Degree of acidosis correlates with severity of renal failure 3
• Anion gap may be normal or elevated even in advanced kidney disease 3
• Chronic metabolic acidosis in CKD is associated with:
  • Muscle wasting
  • Bone disease
  • Impaired growth
  • Hormonal abnormalities
  • Insulin resistance
  • Progression of renal failure 3

Diagnostic Approach

The calculation of serum anion gap is crucial for classification:

• Anion gap = [Na⁺] - ([HCO₃⁻] + [Cl⁻]) 5
• Normal anion gap: 8-12 mEq/L
• Elevated anion gap: >12 mEq/L

Important Clinical Considerations

• Metabolic acidosis in critically ill patients can significantly impact morbidity and mortality 4
• Treatment should focus on addressing the underlying cause rather than just correcting pH 6
• In organic acidosis (like lactic acidosis), the primary goal is improving tissue oxygenation to stop acid production 4
• For chronic metabolic acidosis in CKD, maintaining serum bicarbonate at or above 22 mmol/L is recommended 1
• Sodium bicarbonate therapy may be beneficial in chronic metabolic acidosis but remains controversial in acute organic acidosis 7

Pitfalls to Avoid

• Don't miss the distinction between organic and mineral metabolic acidosis, as their significance and treatment approaches differ significantly 6
• Avoid focusing solely on pH correction without addressing the underlying cause, especially in organic acidosis 6
• Be cautious with sodium bicarbonate therapy in acute metabolic acidosis as it may not improve outcomes and can cause complications like hypercapnia, hypokalemia, and ionized hypocalcemia 7
• Remember that not all patients with ketoacidosis have DKA; consider starvation ketosis and alcoholic ketoacidosis in appropriate clinical settings 1