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Metabolic Acidosis


James L. Lewis III

, MD, Brookwood Baptist Health and Saint Vincent’s Ascension Health, Birmingham

Last full review/revision Jul 2021| Content last modified Jul 2021
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Metabolic acidosis is primary reduction in bicarbonate (HCO3), typically with compensatory reduction in carbon dioxide partial pressure (Pco2); pH may be markedly low or slightly subnormal. Metabolic acidoses are categorized as high or normal anion gap based on the presence or absence of unmeasured anions in serum. Causes include accumulation of ketones and lactic acid, renal failure, and drug or toxin ingestion (high anion gap) and gastrointestinal or renal HCO3 loss (normal anion gap). Symptoms and signs in severe cases include nausea and vomiting, lethargy, and hyperpnea. Diagnosis is clinical and with arterial blood gas (ABG) and serum electrolyte measurement. The cause is treated; IV sodium bicarbonate may be indicated when pH is very low.


Metabolic acidosis is acid accumulation due to

  • Increased acid production or acid ingestion

  • Decreased acid excretion

  • Gastrointestinal or renal HCO3 loss

Acidemia (arterial pH < 7.35) results when acid load overwhelms respiratory compensation. Causes are classified by their effect on the anion gap (see table Causes of Metabolic Acidosis).


Causes of Metabolic Acidosis



High anion gap


Alcohol (chronic abuse)


Lactic acidosis (due to physiologic processes)

Alcohol (chronic abuse)

Primary hypoxia due to lung disorders

Lactic acidosis (due to exogenous toxins)

Biguanides (rare except with acute kidney injury)

Carbon monoxide


HIV nucleoside reverse transcriptase inhibitors




Toluene (initially high gap; subsequent excretion of metabolites normalizes gap)

D-Lactate generation

Toxins metabolized to acids

Ethylene glycol (oxalate)

Methanol (formate)

Paraldehyde (acetate, chloracetate)


Normal anion gap (hyperchloremic acidosis)

Gastrointestinal bicarbonate (HCO3) loss

Calcium chloride (CaCl2)



Enteric fistulas


Magnesium sulfate (MgSO4)

Use of ion-exchange resins

Parenteral infusion


Ammonium chloride (NH4Cl)


Rapid sodium chloride (NaCl) infusion

Renal HCO3 loss



Renal tubular acidosis, types 1, 2, and 4

Tubulointerstitial renal disease

Urologic procedures

Ureteroileal conduit




Toluene (late)

High anion gap acidosis

The most common causes of a high anion gap metabolic acidosis are

  • Ketoacidosis

  • Lactic acidosis

  • Renal failure

  • Toxic ingestions

Ketoacidosis is a common complication of type 1 diabetes mellitus (see diabetic ketoacidosis), but it also occurs with chronic alcohol use disorder (see alcoholic ketoacidosis), undernutrition, and, to a lesser degree, fasting. In these conditions, the body converts from glucose metabolism to free fatty acid (FFA) metabolism; FFAs are converted by the liver into ketoacids, acetoacetic acid, and beta-hydroxybutyrate (all unmeasured anions). Ketoacidosis is also a rare manifestation of congenital isovaleric acidemia or congenital methylmalonic acidemia.

Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. Lactate accumulation results from a combination of excess formation and decreased metabolism of lactate. Excess lactate production occurs during states of anaerobic metabolism. The most serious form occurs during the various types of shock. Decreased metabolism generally occurs with hepatocellular dysfunction from decreased liver perfusion or as a part of generalized shock. Diseases and drugs that impair mitochondrial function can cause lactic acidosis.

Renal failure causes high anion gap acidosis by decreased acid excretion and decreased HCO3 reabsorption. Accumulation of sulfates, phosphates, urate, and hippurate accounts for the high anion gap.

Toxins may have acidic metabolites or trigger lactic acidosis. Rhabdomyolysis is a rare cause of metabolic acidosis thought to be due to release of protons and anions directly from muscle.

Normal anion gap acidosis

The most common causes of normal anion gap acidosis are

  • Gastrointestinal (GI) or renal HCO3 loss

  • Impaired renal acid excretion

Normal anion gap metabolic acidosis is also called hyperchloremic acidosis because the kidneys reabsorb chloride (Cl) instead of reabsorbing HCO3.

Many GI secretions are rich in HCO3 (eg, biliary, pancreatic, and intestinal fluids); loss due to diarrhea, tube drainage, or fistulas can cause acidosis. In ureterosigmoidostomy (insertion of ureters into the sigmoid colon after obstruction or cystectomy), the colon secretes and loses HCO3 in exchange for urinary chloride (Cl) and absorbs urinary ammonium, which dissociates into ammonia (NH3+) and hydrogen ion (H+). Ion-exchange resin uncommonly causes HCO3 loss by binding HCO3.

The renal tubular acidoses impair either H+ secretion (types 1 and 4) or HCO3 absorption (type 2). Impaired acid excretion and a normal anion gap also occur in early renal failure, tubulointerstitial renal disease, and when carbonic anhydrase inhibitors (eg, acetazolamide) are taken.

Symptoms and Signs

Symptoms and signs (see table Clinical Consequences of Acid-Base Disorders) are primarily those of the cause. Mild acidemia is itself asymptomatic. More severe acidemia (pH < 7.10) may cause nausea, vomiting, and malaise. Symptoms may occur at higher pH if acidosis develops rapidly.

The most characteristic sign is hyperpnea (long, deep breaths at a normal rate), reflecting a compensatory increase in alveolar ventilation; this hyperpnea is not accompanied by a feeling of dyspnea.

Pearls & Pitfalls

  • The hyperpnea triggered by metabolic acidosis does not cause a sensation of dyspnea.

Severe, acute acidemia predisposes to cardiac dysfunction with hypotension and shock, ventricular arrhythmias, and coma. Chronic acidemia causes bone demineralization disorders (eg, rickets, osteomalacia, osteopenia).


  • Arterial blood gas (ABG) and serum electrolyte measurement

  • Anion gap and delta gap calculated

  • Winters formula for calculating compensatory changes

  • Testing for cause

Recognition of metabolic acidosis and appropriate respiratory compensation are discussed in Diagnosis of Acid-Base Disorders. Determining the cause of metabolic acidosis begins with the anion gap.

The cause of an elevated anion gap may be clinically obvious (eg, hypovolemic shock, missed hemodialysis), but if not, blood testing should include

  • BUN (blood urea nitrogen)

  • Creatinine

  • Glucose

  • Lactate

  • Possible toxins

Salicylate levels can be measured in most laboratories, but methanol and ethylene glycol frequently cannot; their presence may be suggested by presence of an osmolar gap.

Calculated serum osmolarity (2 [sodium] + [glucose]/18 + BUN/2.8 + blood alcohol/5, based on conventional units) is subtracted from measured osmolarity. A difference > 10 implies the presence of an osmotically active substance, which, in the case of a high anion gap acidosis, is methanol or ethylene glycol. Although ingestion of ethanol may cause an osmolar gap and a mild acidosis, it should never be considered the sole cause of a significant metabolic acidosis.

If the anion gap is normal and no cause is obvious (eg, marked diarrhea), urinary electrolytes are measured and the urinary anion gap is calculated as [sodium] + [potassium] – [chloride]. A normal urinary anion gap (including in patients with gastrointestinal losses) is 30 to 50 mEq/L (30 to 50 mmol/L) ; an elevation suggests renal HCO3 loss (evaluation of renal tubular acidosis is discussed elsewhere).

In addition, when metabolic acidosis is present, a delta gap is calculated to identify concomitant metabolic alkalosis, and Winters formula is applied to determine whether respiratory compensation is appropriate or reflects a second acid-base disorder.


  • Cause treated

  • Sodium bicarbonate (NaHCO3) primarily for severe acidemia—give with caution

Treatment is directed at the cause. Hemodialysis is required for renal failure and sometimes for ethylene glycol, methanol, and salicylate poisoning.

Treatment of acidemia with sodium bicarbonate (NaHCO3) is clearly indicated only in certain circumstances and is probably deleterious in others. When metabolic acidosis results from loss of HCO3 or accumulation of inorganic acids (ie, normal anion gap acidosis), bicarbonate therapy is generally safe and appropriate. However, when acidosis results from organic acid accumulation (ie, high anion gap acidosis), bicarbonate therapy is controversial; it does not clearly decrease mortality in these conditions, and there are several possible risks.

With treatment of the underlying condition, lactate and ketoacids are metabolized back to HCO3; exogenous HCO3 loading may therefore cause an “overshoot” metabolic alkalosis. In any condition, sodium bicarbonate may also cause sodium and volume overload, hypokalemia, and, by inhibiting respiratory drive, hypercapnia. Furthermore, because HCO3 does not diffuse across cell membranes, intracellular acidosis is not corrected and may paradoxically worsen because some of the added HCO3 is converted to carbon dioxide (CO2), which does cross into the cell and is hydrolyzed to H+ and HCO3.

Despite these and other controversies, most experts still recommend giving bicarbonate IV for severe metabolic acidosis (pH < 7.0).

Treatment requires 2 calculations (same for both conventional and SI units). The first is the level to which HCO3 must be raised, calculated by the Kassirer-Bleich equation, using a target value for [H+] of 79 nEq/L (79 nmol/L), which corresponds to a pH of 7.10:

79 = 24 × Pco2/HCO3


Desired HCO3= 0.30 × Pco2

The amount of sodium bicarbonate needed to achieve that level is

NaHCO3 required (mEq/mmol) = (desired [HCO3] observed [HCO3]) × 0.4 × body weight (kg)

For example, a 70-kg man has severe metabolic acidosis with a pH of 6.92, PCO2 40 mmHg and HCO3 of 8 mEq/L (8 mmol/L). The target bicarbonate level needed to achieve a pH of 7.10 is 0.30 × 40 = 12 mEq/L (12 mmol/L). This level is 4 mEq/L (4 mmol/L) more than his current bicarbonate level of 8. To increase bicarbonate by 4, multiply 4 by 0.4 times 70 (the body weight), giving a result of 112 mEq (112 mmol) of HCO3. This amount of sodium bicarbonate is given over several hours. Blood pH and HCO3levels can be checked 30 minutes to 1 hour after administration, which allows for equilibration with extravascular HCO3.

Alternatives to sodium bicarbonate include

  • Lactate, either in the form of lactated Ringer's solution or sodium lactate (is metabolized mEq for mEq to bicarbonate when liver function is normal)

  • Sodium acetate (metabolized mEq for mEq to bicarbonate when liver function is normal)

  • Tromethamine, an amino alcohol that buffers both metabolic (H+) and respiratory (carbonic acid [H2CO3]) acid

  • Carbicarb, an equimolar mixture of sodium bicarbonate and carbonate (the latter consumes CO2 and generates HCO3)

  • Dichloroacetate, which enhances oxidation of lactate

These alternatives do not offer a proven benefit over sodium bicarbonate alone and can cause complications of their own.

Potassium (K+) depletion, common in metabolic acidosis, should be identified through frequent serum K+ monitoring and treated as needed with oral or parenteral potassium chloride.

Key Points

  • Metabolic acidosis can be caused by acid accumulation due to increased acid production or acid ingestion; decreased acid excretion; or gastrointestinal or renal bicarbonate (HCO3) loss.

  • Metabolic acidoses are categorized based on whether the anion gap is high or normal.

  • High anion gap acidoses are most often due to ketoacidosis, lactic acidosis, chronic kidney disease, or certain toxic ingestions.

  • Normal anion gap acidoses are most often due to gastrointestinal or renal HCO3 loss.

  • Calculate delta gap to identify concomitant metabolic alkalosis, and apply Winters formula to see whether respiratory compensation is appropriate or reflects a 2nd acid-base disorder.

  • Treat the cause.

  • Intravenous sodium bicarbonate (NaHCO3) is indicated when acidosis is due to a change in HCO3 level (normal anion gap acidosis).

  • Intravenous sodium bicarbonate is controversial in high anion gap acidosis (but may be considered when pH < 7.00, with a target pH of ≥ 7.10).

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