What are the causes of metabolic acidosis?

Causes of Metabolic Acidosis

Metabolic acidosis develops through three fundamental mechanisms: increased production of acids, decreased excretion of acids, or loss of alkali, and should be systematically classified by anion gap to determine the underlying etiology. 1

Classification by Anion Gap

The first critical step in determining the cause is calculating the anion gap, which divides metabolic acidosis into two major categories 2, 3:

High Anion Gap Metabolic Acidosis (Unmeasured Organic Anions Present)

Lactic Acidosis:

• Primary contributor in shock states from inadequate oxygen delivery to tissues and tissue hypoperfusion 2
• Lactate levels directly indicate tissue hypoxia severity 2
• Septic shock exhibits complex metabolic acidosis with multiple contributors including lactic acidosis 2

Ketoacidosis:

• Diabetic ketoacidosis (DKA): Characterized by elevated plasma glucose, arterial pH <7.3, low bicarbonate, and positive serum/urine ketones 2
• Alcoholic ketoacidosis: Distinguished by lower plasma glucose levels than DKA with clinical history of alcohol use 2
• Starvation ketosis: Presents with serum bicarbonate >18 mEq/L and mildly elevated glucose 2

Renal Failure:

• Chronic renal failure causes high anion gap acidosis due to impaired acid excretion by the kidney 4, 2
• With severe reductions in glomerular filtration rate, anion gap metabolic acidosis eventually develops 5

Toxic Ingestions:

• Salicylate, methanol, and ethylene glycol poisoning 2, 6
• The osmolal gap can be elevated in methanol, ethylene glycol, and propylene glycol ingestions 2
• Barbiturate intoxications 6

Normal Anion Gap (Hyperchloremic) Metabolic Acidosis

Gastrointestinal Bicarbonate Loss:

• Severe diarrhea accompanied by significant bicarbonate loss 6, 7
• Loss of NaHCO3 reduces effective extracellular volume, increasing chloride reabsorption from the diet 5

Renal Tubular Acidosis (RTA):

• Distal RTA: Primary defect in renal acidification where renal input of new bicarbonate is insufficient to regenerate bicarbonate lost in buffering endogenous acid 5
• Proximal RTA: Filtered bicarbonate is lost by kidney wasting 5
• Both conditions result in hyperchloremic normal gap metabolic acidosis due to increased chloride reabsorption 5

Early Renal Failure:

• Before severe GFR reduction develops into high anion gap acidosis 7, 5

Drug-Induced:

• Medications causing hyperkalemia 7

Exogenous Acid Administration:

• Direct administration of acids 7

Special Clinical Contexts

Chronic Low-Grade Acidosis:

• Dietary-induced from high animal protein intake and low fruit/vegetable consumption, creating an imbalance between nonvolatile acids and available alkali 2

Circulatory Insufficiency:

• Shock or severe dehydration states 6

Cardiac Arrest:

• Requires vigorous bicarbonate therapy where rapid increase in plasma CO2 content is crucial 6

Extracorporeal Circulation:

• During blood circulation procedures 6

Hemolytic Reactions:

• Requiring alkalinization of urine to diminish nephrotoxicity of hemoglobin breakdown products 6

Diagnostic Approach

Essential Laboratory Assessments:

• Calculate anion gap first to categorize the acidosis 2, 3
• Blood lactate measurement in shock states, with serial measurements providing information about severity and treatment response 2
• Serum ketones to distinguish ketoacidosis from other causes 2
• Osmolal gap for suspected toxic ingestions 2
• Urine pH and urine anion gap or osmolal gap to distinguish renal from extrarenal causes 5
• Serum potassium levels may be useful in certain settings 3

Clinical Consequences Requiring Treatment

Metabolic acidosis in chronic kidney disease and maintenance dialysis patients causes increased protein degradation, decreased albumin synthesis, low plasma branched chain amino acids, and impaired growth 4, 8. Serum bicarbonate should be maintained at or above 22 mmol/L in dialysis patients to prevent these complications 4.