Causes of Metabolic Acidosis
Metabolic acidosis results from three primary mechanisms: excessive acid production, bicarbonate loss, or impaired renal acid excretion, and is classified by the presence or absence of an elevated anion gap. 1
Classification by Anion Gap
The first step in determining the etiology is calculating the serum anion gap: [Na⁺] - ([HCO₃⁻] + [Cl⁻]). 2, 3
High Anion Gap Metabolic Acidosis (Elevated Unmeasured Anions)
Lactic Acidosis
- Primary contributor in shock states from inadequate oxygen delivery and tissue hypoperfusion 1
- Lactate levels >2 mmol/L indicate tissue hypoxia and correlate with mortality 4
- Serial lactate measurements guide shock severity assessment and treatment response 1, 4
- Septic shock exhibits complex acidosis with multiple contributors including lactic acidosis and hyperchloremic acidosis 1, 4
Ketoacidosis
- Diabetic ketoacidosis (DKA): glucose typically >250 mg/dL, pH <7.3, bicarbonate <15 mEq/L, positive serum/urine ketones 1
- Alcoholic ketoacidosis (AKA): glucose low or normal (rarely >250 mg/dL) with recent heavy alcohol intake history 1
- Starvation ketosis: bicarbonate ≥18 mEq/L with mildly elevated glucose 1
Renal Failure
- Chronic kidney disease presents with high anion gap acidosis due to impaired acid excretion and accumulation of unmeasured anions 1, 5
- With severe GFR reduction, anion gap acidosis eventually develops 5
Toxic Ingestions
- Salicylates, methanol, ethylene glycol, and paraldehyde cause high anion gap acidosis 1
- Elevated osmolal gap suggests methanol, ethylene glycol, or propylene glycol ingestion 1
Rare Metabolic Disorders
- Organic acidemias (methylmalonic, propionic, isovaleric acidemia) present with toxic encephalopathy, vomiting, and neurologic symptoms 1
Normal (Hyperchloremic) Anion Gap Metabolic Acidosis
Gastrointestinal Bicarbonate Loss
- Diarrhea causes direct bicarbonate loss 2, 5
- Sodium bicarbonate replacement is useful in these cases 6
Renal Tubular Acidosis (RTA)
- Proximal RTA (Type 2): filtered bicarbonate is lost by kidney wasting, commonly linked to Fanconi syndrome with concurrent urinary losses of phosphate, uric acid, glucose, and amino acids 1, 5
- Distal RTA (Type 1): primary defect in renal acidification with insufficient new bicarbonate input to regenerate buffering capacity 1, 5
- RTA of renal insufficiency: insufficient bicarbonate regeneration to buffer endogenous acid 5
- Assessment of urinary ammonium excretion via urine anion gap or osmolal gap distinguishes renal from extrarenal causes 5
Dietary-Induced Acidosis
- High animal protein intake with low fruit/vegetable consumption creates imbalance between nonvolatile acids and available alkali 1
Diagnostic Approach Algorithm
Measure arterial blood gas and basic metabolic panel to confirm metabolic acidosis: pH <7.35, HCO₃⁻ <22 mmol/L 3
For high anion gap acidosis:
- Measure blood lactate in shock states 1, 4
- Check serum/urine ketones and plasma glucose to distinguish DKA (glucose >250 mg/dL) from AKA (glucose normal/low) from starvation ketosis (HCO₃⁻ ≥18 mEq/L) 1
- Evaluate renal function (BUN/creatinine) for uremic acidosis 1
- Calculate osmolal gap if toxic ingestion suspected 1
For normal anion gap acidosis:
Search for mixed acid-base disorders in critically ill patients, as concurrent high and normal anion gap acidosis are common 1
Critical Pitfalls to Avoid
- Do not assume a single cause in critically ill patients; actively search for mixed disorders 1
- Do not overlook life-threatening causes such as septic shock, mesenteric ischemia, or toxic ingestions requiring immediate specific interventions 4
- Blood urea nitrogen-to-creatinine ratio ≈0.8 effectively rules out stage V chronic kidney disease (which shows ratio >20:1) 1
- In severe metabolic acidosis with compensatory hyperventilation (low PaCO₂), non-invasive ventilation would be harmful by interfering with compensation 4