What are the causes of metabolic acidosis?

Causes of Metabolic Acidosis

Metabolic acidosis is classified by anion gap into two major categories: high anion gap acidosis (caused by accumulation of unmeasured organic anions) and normal anion gap acidosis (caused by bicarbonate loss or impaired renal acid excretion). 1

High Anion Gap Metabolic Acidosis

The primary causes involve accumulation of organic acids that consume bicarbonate:

Lactic Acidosis

• Most common cause in critically ill patients, resulting from inadequate oxygen delivery to tissues and tissue hypoperfusion in shock states 1, 2
• Lactate levels serve as a key indicator of tissue hypoxia and correlate with mortality, with levels >2 mmol/L indicating significant tissue hypoperfusion 2
• Septic shock produces complex metabolic acidosis with contributions from both lactic acidosis and hyperchloremic acidosis 1, 2

Ketoacidosis

• Diabetic ketoacidosis (DKA) is characterized by elevated plasma glucose, arterial pH <7.30, bicarbonate <18 mEq/L, and positive serum/urine ketones, resulting from insulin deficiency coupled with elevated counterregulatory hormones (glucagon, catecholamines, cortisol, growth hormone) that promote lipolysis and unrestrained hepatic fatty acid oxidation to ketone bodies (β-hydroxybutyrate and acetoacetate) 3, 1
• Alcoholic ketoacidosis is distinguished from DKA by lower or normal plasma glucose levels and clinical history of alcohol use 1
• Starvation ketosis presents with serum bicarbonate >18 mEq/L and mildly elevated glucose 1

Renal Failure

• Chronic renal failure causes high anion gap acidosis due to impaired renal acid excretion and accumulation of organic anions 1

Toxic Ingestions

• Salicylate, methanol, and ethylene glycol poisoning produce high anion gap metabolic acidosis 1
• The osmolal gap is elevated in methanol, ethylene glycol, and propylene glycol ingestions, providing a diagnostic clue 1

Normal Anion Gap (Hyperchloremic) Metabolic Acidosis

These disorders result from bicarbonate loss or impaired renal acidification:

Gastrointestinal Bicarbonate Loss

• Diarrhea, intestinal fistulas, and ureterosigmoidostomy cause direct bicarbonate losses 4, 5

Renal Tubular Acidosis

• Type IV renal tubular acidosis commonly occurs in diabetic patients with hyperkalemia 6
• Other forms of RTA involve impaired renal bicarbonate reabsorption or hydrogen ion secretion 5

Early Renal Failure

• Before significant accumulation of organic anions, renal failure may present as hyperchloremic acidosis 4

Drug-Induced

• Medications causing hyperkalemia and impaired renal acidification 4

Dietary Factors

• Chronic low-grade acidosis from high animal protein intake with low fruit and vegetable consumption creates an imbalance between nonvolatile acids and available alkali 1

Diagnostic Approach

Calculate the anion gap first ([Na+] - [HCO3- + Cl-]) to categorize the acidosis, as this directs subsequent evaluation 5, 7:

• For high anion gap acidosis: Measure blood lactate in shock states, serum ketones to identify ketoacidosis, assess renal function, obtain toxicology screening, and calculate osmolal gap if toxic ingestion suspected 1, 2
• For normal anion gap acidosis: Evaluate for gastrointestinal bicarbonate losses, measure urine pH and electrolytes to assess for renal tubular acidosis, and review medication history 5
• Serial measurements of lactate, base deficit, and pH provide valuable information about shock severity and treatment response 2

Important Caveat

Mixed acid-base disorders are common—a patient may have both high anion gap and hyperchloremic acidosis simultaneously, particularly during treatment of DKA when the anion gap normalizes but hyperchloremic acidosis develops 6, 5.