What are the causes of metabolic acidosis?

Causes of Metabolic Acidosis

Metabolic acidosis is defined as a blood pH below 7.35 (corresponding to a hydrogen ion concentration greater than 45 nmol/L) with decreased serum bicarbonate levels, and can be classified into anion gap and non-anion gap types based on the underlying etiology. 1

Classification of Metabolic Acidosis

Anion Gap Metabolic Acidosis (>12 mEq/L)

• Lactic acidosis

  • Tissue hypoxia (shock, severe dehydration, circulatory insufficiency) 2, 3
  • Severe primary lactic acidosis 3

• Ketoacidosis

  • Diabetic ketoacidosis (uncontrolled diabetes) 1, 3
  • Alcoholic ketoacidosis
  • Starvation ketoacidosis
  • Drug-induced ketoacidosis (corticosteroids, thiazides, sympathomimetic agents) 1

• Renal failure (severe renal disease) 3, 4

  • Accumulation of unmeasured anions 5
  • Impaired acid excretion 6

• Toxin ingestion

  • Salicylate poisoning 3
  • Methanol poisoning 3
  • Ethylene glycol poisoning 1

Normal Anion Gap (Hyperchloremic) Metabolic Acidosis

• Gastrointestinal bicarbonate loss

  • Severe diarrhea 3
  • Intestinal or pancreatic fistulas

• Renal tubular acidosis

  • Proximal (Type 2) RTA - impaired bicarbonate reabsorption 5, 7
  • Distal (Type 1) RTA - impaired acid secretion
  • Hypoaldosteronism (Type 4) RTA

• Other causes

  • Rapid administration of chloride-rich solutions
  • Carbonic anhydrase inhibitors
  • Dilutional acidosis

Diagnostic Approach

1. Calculate the anion gap: [Na+] - ([Cl-] + [HCO3-]), normal range 8-12 mEq/L 1

   • Elevated (>12 mEq/L): Consider anion gap metabolic acidosis
   • Normal (8-12 mEq/L): Consider non-anion gap metabolic acidosis

2. Laboratory assessment:

   • Arterial blood gases
   • Complete metabolic panel
   • Serum ketones
   • Serum lactate
   • Serum osmolality (to check for osmolal gap in toxic alcohol ingestion)
   • Urinalysis 1

3. Assess severity:

   • Mild: Total CO2 ≥19 mmol/L
   • Moderate to Severe: Total CO2 <19 mmol/L 1

Management Principles

The treatment of metabolic acidosis should primarily focus on addressing the underlying cause 4:

1. Fluid resuscitation: Initial therapy with isotonic saline at 15-20 mL/kg/hr for most causes 1

2. Specific therapies:

   • Insulin for diabetic ketoacidosis 1
   • Fomepizole or ethanol for toxic alcohol ingestion 1
   • Hemodialysis for severe acidosis, renal failure, or toxic alcohol levels ≥50 mg/dL 1

3. Bicarbonate therapy:

   • Consider for severe acidosis (pH <7.2) 1
   • Dosing: 1-2 mEq/kg sodium bicarbonate over 1 hour 1
   • Note: Bicarbonate therapy remains controversial in certain conditions like lactic acidosis 5
   • For chronic metabolic acidosis in CKD: Aim for serum bicarbonate ≥22 mmol/L 7

Clinical Pitfalls and Caveats

• Mixed acid-base disorders are common and can complicate diagnosis
• Compensatory mechanisms may mask the severity of the primary disorder
• Overcorrection of acidosis can lead to metabolic alkalosis and associated complications
• Bicarbonate therapy side effects include hypercapnia, hypokalemia, ionized hypocalcemia, and QTc interval prolongation 5
• Serial monitoring of acid-base status is crucial to assess response to treatment 1
• Chronic metabolic acidosis can lead to increased muscle degradation and abnormal bone metabolism if left untreated 4

The approach to metabolic acidosis requires careful assessment of the underlying cause, appropriate classification based on anion gap, and targeted therapy directed at the primary disorder while monitoring for potential complications of both the acidosis and its treatment.