Causes of Metabolic Acidosis
Metabolic acidosis develops from three fundamental mechanisms: rapid production of nonvolatile acids, abnormal bicarbonate losses, or impaired renal acid excretion, and the first diagnostic step is determining whether an anion gap is present. 1
Classification by Anion Gap
The anion gap (calculated as [Na+] - [HCO3-] - [Cl-]) divides metabolic acidosis into two major categories that guide diagnosis 2:
High Anion Gap Metabolic Acidosis
This occurs when endogenous acids accumulate and consume bicarbonate 3:
- Lactic acidosis is the most common cause in critically ill patients, resulting from inadequate oxygen delivery to tissues during shock states, with lactate levels >2 mmol/L indicating tissue hypoxia 4
- Ketoacidosis produces organic anions (beta-hydroxybutyrate and acetoacetate), most commonly in diabetic ketoacidosis 5
- Renal failure causes accumulation of unmeasured anions when the kidney cannot excrete acids 3
- Toxic ingestions including ethylene glycol, methanol, salicylate, pyroglutamic acid (5-oxoproline), propylene glycol, or djenkol bean poisoning 3
A critical caveat: In septic shock, metabolic acidosis is complex with contributions from lactic acidosis, hyperchloremic acidosis, and increased strong ion gap occurring simultaneously 4
Non-Anion Gap (Hyperchloremic) Metabolic Acidosis
This pattern occurs when bicarbonate is lost and chloride increases to maintain electroneutrality 6:
- Gastrointestinal bicarbonate losses from diarrhea or intestinal fistulas are the most common cause 3
- Renal tubular acidosis represents impaired renal acid excretion or bicarbonate reabsorption 3
- Early renal failure before significant anion accumulation occurs 3
- Drug-induced hyperkalemia affecting renal acid handling 3
- Iatrogenic causes from administration of acids or unbalanced electrolyte solutions containing excess chloride, which can worsen kidney-related outcomes 7
- Recovery phase of diabetic ketoacidosis produces transient hyperchloremic acidosis as chloride from IV fluids replaces ketoanions lost during osmotic diuresis; this is biochemically insignificant and requires no specific intervention unless acute renal failure or extreme oliguria develops 6
Pathophysiologic Mechanism
When bicarbonate is lost, effective extracellular volume decreases, triggering increased renal chloride reabsorption from dietary sources to maintain electroneutrality, which decreases the strong ion difference and lowers pH 6. This explains why hyperchloremia accompanies normal anion gap acidosis.
Diagnostic Approach Beyond Anion Gap
Additional parameters refine the diagnosis 1:
- Osmolal gap helps identify toxic alcohol ingestions in high anion gap acidosis 1
- Urine pH distinguishes renal tubular acidosis (inappropriately high urine pH >5.5) from gastrointestinal losses (appropriately low urine pH <5.5) 1
- Serum potassium differentiates types of renal tubular acidosis and identifies drug-induced causes 1
- Serial lactate, base deficit, and pH measurements assess shock severity and treatment response, with base deficit being an independent predictor of mortality in traumatic hemorrhagic shock 4
Important pitfall: The rise in anion gap usually equals the fall in plasma bicarbonate in pure high anion gap acidosis; discrepancies suggest mixed acid-base disorders 5