What are the common causes of metabolic acidosis?

Metabolic Acidosis Causes

Metabolic acidosis results from three fundamental mechanisms: accumulation of endogenous acids that consume bicarbonate, loss of bicarbonate from the gastrointestinal tract or kidneys, or impaired renal acid excretion. 1, 2

Classification by Anion Gap

The anion gap is the critical first step in determining etiology, dividing metabolic acidosis into two major categories 3, 1:

High Anion Gap Metabolic Acidosis (Unmeasured Anions Present)

Lactic acidosis:

• Primary contributor in shock states from inadequate tissue oxygen delivery and hypoperfusion 3
• Blood lactate measurement is essential in shock, with serial measurements indicating severity and treatment response 3
• Septic shock exhibits complex metabolic acidosis with multiple contributors including lactic acidosis 3

Ketoacidosis variants:

• Diabetic ketoacidosis (DKA): plasma glucose typically >250 mg/dL, arterial pH <7.3, bicarbonate <15 mEq/L, positive serum/urine ketones 3
• Alcoholic ketoacidosis: low or normal glucose (rarely >250 mg/dL) with clinical history of recent heavy alcohol intake 3
• Starvation ketosis: serum bicarbonate ≥18 mEq/L with mildly elevated glucose 3

Renal failure:

• Chronic kidney disease presents as high anion gap acidosis due to impaired renal acid excretion 3
• With severe GFR reduction, anion gap metabolic acidosis eventually develops 2

Toxic ingestions:

• Salicylates, methanol, ethylene glycol, and paraldehyde cause high anion gap metabolic acidosis 3
• Osmolal gap is elevated in methanol, ethylene glycol, and propylene glycol ingestions 3

Rare metabolic disorders:

• Organic acidemias (methylmalonic acidemia, propionic acidemia, isovaleric acidemia) present with toxic encephalopathy, vomiting, and neurologic symptoms 4

Normal Anion Gap (Hyperchloremic) Metabolic Acidosis

Gastrointestinal bicarbonate losses:

• Diarrhea and other GI losses where bicarbonate is effectively replaced by chloride 2, 5

Renal tubular acidosis:

• Distal (Type 1) RTA: primary defect in renal acidification with insufficient new bicarbonate generation 2
• Proximal (Type 2) RTA: filtered bicarbonate lost by kidney wasting, commonly linked to Fanconi syndrome with concurrent urinary losses of phosphate, uric acid, glucose, and amino acids 3, 2
• Both result in hyperchloremic acidosis because loss of NaHCO₃ or NaA reduces effective extracellular volume, increasing dietary chloride reabsorption 2

Early renal failure:

• RTA of renal insufficiency characterized by normal gap acidosis initially 2, 5

Drug-induced hyperkalemia and exogenous acid administration 5

Diagnostic Approach Algorithm

Step 1: Calculate anion gap to categorize the acidosis 3, 1

Step 2 for high anion gap:

• Measure serum or urine ketones to identify ketoacidosis 3
• Check plasma glucose: >250 mg/dL favors DKA; normal-to-low suggests alcoholic ketoacidosis or starvation 3
• Evaluate renal function (BUN/creatinine) for uremic acidosis 3
• Calculate osmolal gap if toxic ingestion suspected 3

Step 3 for normal anion gap:

• Calculate urine anion gap or osmolal gap to assess urinary ammonium excretion, distinguishing renal from extrarenal causes 2
• Check urine pH and serum potassium 1
• Evaluate for GI losses, RTA patterns, or medication effects 2, 5

Critical Clinical Pitfalls

Mixed acid-base disorders are common in critically ill patients; actively search for concurrent high anion gap and normal anion gap metabolic acidosis rather than assuming a single cause. 3

Dietary-induced chronic low-grade acidosis can occur with high animal protein intake and low fruit/vegetable consumption, creating an imbalance between nonvolatile acids and available alkali 3

In chronic kidney disease, maintain serum bicarbonate ≥22 mmol/L to prevent increased protein degradation, decreased albumin synthesis, and impaired growth 3