Causes of Metabolic Acidosis
Metabolic acidosis results from either accumulation of endogenous acids that consume bicarbonate (high anion gap) or loss of bicarbonate from the gastrointestinal tract or kidneys (normal anion gap/hyperchloremic). 1
Classification by Anion Gap
The first critical step in determining etiology is calculating the anion gap (Na+ - [Cl- + HCO3-]), which categorizes metabolic acidosis into two major types 2, 3:
High Anion Gap Metabolic Acidosis (>10-12 mEq/L)
High anion gap acidosis indicates the presence of unmeasured organic anions in the body. 2, 4
Lactic acidosis - The primary contributor in shock states, resulting from inadequate oxygen delivery to tissues and tissue hypoperfusion, with lactate levels >2 mmol/L indicating tissue hypoxia 5, 1
Diabetic ketoacidosis (DKA) - Characterized by plasma glucose >250 mg/dl, arterial pH <7.3, bicarbonate <15 mEq/l, and positive serum/urine ketones (β-hydroxybutyrate and acetoacetate) 2
Alcoholic ketoacidosis - Distinguished from DKA by plasma glucose ranging from mildly elevated (rarely >250 mg/dl) to hypoglycemia, with clinical history of alcohol use 2
Starvation ketosis - Serum bicarbonate usually not lower than 18 mEq/l, with mildly elevated glucose 2
Chronic renal failure - Impaired acid excretion by the kidney, though this can also present as hyperchloremic acidosis 2
Toxic ingestions - Salicylate, methanol, ethylene glycol (indicated by calcium oxalate and hippurate crystals in urine), paraldehyde (characteristic strong odor on breath), pyroglutamic acid, propylene glycol 2, 1
Normal Anion Gap Metabolic Acidosis (Hyperchloremic)
Normal anion gap acidosis results from bicarbonate loss or impaired renal acid excretion, with chloride retention maintaining electroneutrality. 1, 4
Gastrointestinal bicarbonate loss - Diarrhea, intestinal or pancreatic fistulas, ureterosigmoidostomy 1, 4
Renal tubular acidosis - Impaired renal hydrogen ion excretion or bicarbonate reabsorption 1
Type IV renal tubular acidosis in diabetes - Associated with hyperkalemia and hypoaldosteronism 6
Early renal failure - Before development of high anion gap acidosis 1
Drugs causing hyperkalemia - Various medications that impair renal potassium and acid handling 1
Administration of acidifying chloride salts - Ammonium chloride, arginine hydrochloride 1, 4
Special Clinical Contexts
Septic Shock
Septic shock exhibits complex metabolic acidosis with multiple contributors: lactic acidosis from tissue hypoperfusion, hyperchloremic acidosis from resuscitation fluids, and increased strong ion gap 5
Dietary-Induced Chronic Low-Grade Acidosis
High animal protein intake (especially red meat) combined with low fruit and vegetable consumption creates an imbalance between nonvolatile acids (from sulfur-containing amino acids) and available alkali (from potassium citrate salts in fruits/vegetables), leading to chronic low-grade metabolic acidosis that worsens with declining kidney function 2
Diagnostic Approach
When etiology is not immediately apparent from history and physical examination, determine if the acidosis is hyperchloremic or high-anion-gap type first. 3
Additional diagnostic tools include:
Osmolal gap - Elevated in methanol, ethylene glycol, and propylene glycol ingestions 2
Urine pH - Helps differentiate renal tubular acidosis types 7
Serum potassium - Elevated in type IV RTA and certain drug-induced acidoses 7, 6
Blood lactate measurement - Essential in shock states, with serial measurements providing information about shock severity and treatment response 5
Serum ketones - Distinguishes ketoacidosis from other causes 2