Metabolic acidosis - NYSORA

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Metabolic acidosis

Learning objectives

  • Describe the physiology, causes, and effects of metabolic acidosis
  • Diagnose metabolic acidosis
  • Manage metabolic acidosis


  • Metabolic acidosis is a disturbance in the homeostasis of plasma acidity
  • Any process that increases the serum hydrogen ion concentration is a distinct acidosis
  • A patient can have multiple acidoses contributing to the decrease of serum pH
  • Adicosis can be either respiratory (changes in CO2) or metabolic (changes in bicarbonate)
  • Metabolic acidosis is characterized by an increase in serum hydrogen ion concentration resulting in serum bicarbonate (HCO3) <24 mEq/L
  • May be associated with organ failure, especially respiratory and cardiovascular
  • Can be acute or chronic


  • Classification of metabolic acidosis is based on the presence or absence of an anion gap (concentration of unmeasured serum anions)
  • Sodium, the main plasma cation, is balanced by the sum of the anions bicarbonate and chloride in addition to the unmeasured anions (e.g., lactate, acetoacetate), which represent the anion gap
  • Anion gap metabolic acidosis is often caused by anaerobic metabolism and lactic acid accumulation
  • Non-gap metabolic acidosis is primarily caused by the loss of bicarbonate (e.g., diarrhea, renal tubular acidosis)
  • Causes:
Anion gap metabolic acidosisNon-gap metabolic acidosis associated with normal or high serum K+Non-gap metabolic acidosis associated with low serum K+
Acute kidney injuryAdministration of HCl or precursors
Chronic kidney disease
Administration of cationic amino acids
intestinal, pancreatic, or biliary fistula
Diabetic ketoacidosisChronic kidney disease
Proximal renal tubular acidosis
Alcoholic ketoacidosisAdrenal insufficiency (primary or secondary)Distal renal tubular acidosis
Lactic acidosis Hyporeninemic hypoaldosteronismUreterosigmoidostomy
Salicylate intoxicationHyperkalemic distal renal tubular acidosisUreteroileostomy
Toxic alcohol intoxication (methanol, ethylene glycol,
diethylene glycol, propylene glycol)
Pseudoaldosteronism type IDiabetic ketoacidosis
Pyroglutamic acidosisPseudoaldosteronism type II (Gordon’s syndrome)Toluene intoxication
Fasting ketoacidosis
Drugs (spironolactone, prostaglandin inhibitors, triamterene, amiloride, trimethoprim, pentamidine,
Lactic acidosis
Toluene intoxication

Adverse effects

Acute metabolic acidosisChronic metabolic acidosis
Impaired leukocyte functionGeneration or exacerbation of bone disease
Predisposition to ventricular arrhythmiasGrowth retardation (in children)
Arterial vasodilation and hypotensionImpaired glucose tolerance
Resistance to action of infused catecholaminesAcceleration of progression of kidney disease
Resistance to action of insulinIncreased muscle wasting
Suppression of lymphocyte functionReduced albumin synthesis
Impaired cellular energy productionEnhanced production of β2-microglobulin
Stimulation of apoptosis
Changes in mental status
Stimulation of interleukin production
Alteration in oxygen binding to hemoglobin
Decreased cardiac contractility and cardiac output


  • History: Identify potential causes (vomiting, diarrhea, medications, possible overdoses, chronic conditions such as diabetes mellitus)
  • Physical examination: dry mucus membranes in diabetic ketoacidosis, compensatory hyperventilation
  • Lab tests;
    • Blood pH <7.35
    • pCO2: 
      • >40-45: respiratory acidosis
      • <40: metabolic acidosis
    • Anion gap
      • Anion gap = Na+ – (Cl- + HCO3-)
      • Normal anion gap = 12
      • Anion gap >12: Anion gap metabolic acidosis
    • Respiratory compensation
      • Winter’s formula: Expected CO2 = (HCO3- x 1.5) + 8 +/- 2
      • If pCO2 is within the predicted range, there is no additional respiratory disturbance
      • If pCO2 is greater than expected, there is an additional respiratory acidosis
      • If pCO2 is less than expected, there is an additional respiratory alkalosis
    • Additional metabolic disturbances
      • If anion gap is present, determine delta gap
      • Delta gap = Delta anion gap – Delta HCO3- = (anion gap – 12) – (24 – HCO3-)
      • Delta gap < -6: Non anion gap metabolic acidosis
      • Delta gap >6: underlying metabolic alkalosis
      • Delta gap between -6 and 6: only anion gap metabolic acidosis


  • Address the cause of acidosis
  • Fluid resuscitation and electrolyte imbalance correction for sepsis and diabetic ketoacidosis
  • Antidotes for poisoning, dialysis, antibiotics, bicarbonate administration

metabolic acidosis, lactic acidosis, lactic acid, anaerobic, catecholamine, fluid resuscitation, base, ketoacidosis, ketosis, glucose, insulin, cardiovascular, acidemia, renal acidosis, oliruria, uremia, fluid overload, abdominal compartment syndrome, diuretic, hyperkalemia, sodium bicarbonate, tromethamine

Suggested reading

  • Burger MK, Schaller DJ. Metabolic Acidosis. [Updated 2022 Jul 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:
  • Fleisher, Lee A., and Stanley H. Rosenbaum. Complications in Anesthesia. Elsevier, 2018. 
  • Kraut, J., Madias, N. Metabolic acidosis: pathophysiology, diagnosis and management. Nat Rev Nephrol 6, 274–285 (2010).

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