Acid-base disorders

Last updated: November 2, 2023

Summarytoggle arrow icon

Acid-base disorders are characterized by changes in the concentration of hydrogen ions (H+) in the body. Increased H+ concentration (acidosis) can lead to an abnormally low blood pH (acidemia) and decreased H+ concentration (alkalosis) can lead to an abnormally high blood pH (alkalemia); however, if compensation occurs, acidosis and/or alkalosis may be present without acidemia or alkalemia. Acidosis and alkalosis may be respiratory or metabolic in origin depending on the cause of the imbalance; they can also coexist as mixed acid-base disorders. Diagnosis is made based on arterial blood gas (ABG) results. In metabolic acidosis, calculation of the anion gap can also help determine the cause and reach a precise diagnosis. In metabolic alkalosis, urine chloride (Cl‑) concentration can help identify the cause. Treatment is based on the underlying cause.

Definitiontoggle arrow icon

  • Acid-base processes [1]
    • Acidosis: the processes by which H+ concentration is increased
    • Alkalosis: the processes by which H+ concentration is decreased
  • pH scale
    • A logarithmic scale that expresses the acidity or alkalinity of a solution based on the concentration of H+ (pH = -log[H+])
    • Neutral pH is 7; lower values are acidic and higher values are alkaline.
  • Blood pH abnormalities

Pathophysiologytoggle arrow icon

  • The Henderson-Hasselbalch equation allows for the calculation of pH from HCO3- and PCO2: pH = 6.1 + log([HCO3-]/[0.03 × pCO2])
Pathophysiology of acid-base disorders [2]
Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis
  • Expected compensatory response: ↓
  • Expected compensatory response: ↑
  • Expected compensatory response: ↑
  • Expected compensatory response: ↓
  • ↑ Production and/or ingestion of H+ or loss of HCO3-
  • Loss of H+ or ↑ production/ingestion of HCO3-
Compensation mechanisms in acid-base disorders

Diagnosticstoggle arrow icon

Approach to acid-base disorders [1][3]

Careful clinical evaluation is an important first step in the assessment of acid-base disorders, as it can provide important diagnostic clues that can help determine the underlying cause.

Initial blood gas analysis

There are different methods for the assessment of acid-base status; the following method is just one example.

Suggested approach

  1. Evaluate blood pH (reference range: 7.35–7.45).
  2. Evaluate HCO3- (reference range: 22–28 mEq/L).
  3. Evaluate PCO2 (reference range: 33–45 mm Hg).


Further considerations

SMORE: change in PCO2 in the Same direction as pH Metabolic disorder; change in PCO2 in the Opposite direction to pH REspiratory disorder

Corrections to central venous blood gas values [6][7]

Reference values for venous blood gas (VBG) are different from those for ABG; central VBG results can be corrected to approximate ABG.

Compensation (acid-base) [1][8]

  • Definition: physiological changes that occur in acid-base disorders in an attempt to maintain normal body pH
  • Compensatory changes
  • Assessment and interpretation: Calculate the expected compensation; see “Calculation of compensatory response.”
Calculation of compensatory response
Primary acid-base disturbance Expected compensation [1][9]
Metabolic acidosis
  • Winter formula: expected PCO2 (mm Hg) = (1.5 × HCO3-) + 8 ± 2
  • OR (rule of thumb) expected PCO2 (mm Hg) = last two digits of the pH value
Metabolic alkalosis
  • Expected PCO2 (mm Hg) = [0.7 × (HCO3- - 24)] + 40 ± 2
  • OR expected PCO2 (mm Hg) = HCO3- + 15

Respiratory acidosis

  • Expected HCO3- (mEq/L) = 24 + [0.1 × (PCO2 - 40)]
  • OR expected HCO3- (mEq/L): HCO3- increases by 1 mEq/L for every 10 mm Hg increase in PCO2 above 40 mm Hg.
  • Expected HCO3- (mEq/L) = 24 + [0.35 × (PCO2 - 40)]
  • OR expected HCO3- (mEq/L): HCO3- increases by 4–5 mEq/L for every 10 mm Hg increase in PCO2 above 40 mm Hg.

Respiratory alkalosis

  • Expected HCO3- (mEq/L) = 24 - [0.2 × (40 - PCO2)]
  • OR expected HCO3- (mEq/L): HCO3- decreases by 2 mEq/L for every 10 mm Hg decrease in PCO2 below 40 mm Hg.
  • Expected HCO3- (mEq/L) = 24 - [0.4 × (40 - PCO2)]
  • OR expected HCO3- (mEq/L): HCO3- decreases by 4–5 mEq/L for every 10 mm Hg decrease in PCO2 below 40 mm Hg.

Discordance between the measured compensatory response and the expected compensatory response suggests a secondary acid-base disturbance.

In primary metabolic disorders, respiratory compensation develops quickly (within hours), whereas metabolic compensation may take 2–5 days to develop in primary respiratory disorders.

Metabolic acidosistoggle arrow icon

General principles

  • Calculation of the anion gap is the first step in the evaluation of metabolic acidosis.
  • The measured serum sodium (Na+), not the corrected serum Na+, should be used in the formulas, even if glucose levels are high.
  • Depending on the results, further evaluation and calculations may be needed (see specific subsections below).
Metabolic acidosis formulas [1][10][11]
Anion gap Serum anion gap
Urine anion gap
  • [Urine Na+] + [urine K+] - [urine Cl-]
Osmolal gap Serum osmolal gap
Urine osmolal gap
Delta gap

High anion gap metabolic acidosis [1][11]

Review clinical features and initial studies and follow a stepwise approach to identify the underlying cause of high anion gap metabolic acidosis.

  1. Exclude accumulation of endogenous organic acids.
  2. Consider accumulation of exogenous organic acids (ingestion) as the cause: e.g., if the cause remains unclear, or initially if the patient is comatose
  3. Calculate the delta gap: to exclude concomitant acid-base disturbances
Etiology of high anion gap metabolic acidosis
Mechanism Causes
Accumulation of endogenous organic acids
Accumulation of exogenous organic acids

Causes of high anion gap acidosis (MUDPILES): Methanol toxicity, Uremia, Diabetic ketoacidosis, Paraldehyde, Isoniazid or Iron overdose, Inborn error of metabolism, Lactic acidosis, Ethylene glycol toxicity, Salicylate toxicity

Concomitant acid-base disturbances [10][11]

Calculation of the delta gap can help determine if another acid-base disturbance is present in addition to a high anion gap metabolic acidosis. Cut-off values may vary depending on the source.

Normal anion gap metabolic acidosis

Review clinical features and initial studies and consider further diagnostic workup to determine the underlying cause of normal anion gap metabolic acidosis.

Etiology of normal anion gap metabolic acidosis
Mechanism Causes
Loss of bicarbonate (negative urine anion gap)
Decreased renal acid excretion (positive urine anion gap)

Causes of normal anion gap acidosis (FUSEDCARS): Fistula (biliary, pancreatic), Ureterogastric conduit, Saline administration, Endocrine (Addison disease, hyperparathyroidism), Diarrhea, Carbonic anhydrase inhibitors, Ammonium chloride, Renal tubular acidosis, Spironolactone

A neGUTive urine anion gap may be due to GI loss of bicarbonate.

Abnormal anion gap without metabolic acidosis [15]

Metabolic alkalosistoggle arrow icon

Approach [1]

Elevated calcium with renal failure suggests milk-alkali syndrome.


Etiology of metabolic alkalosis [1][17]
Mechanism Causes
Chloride-responsive metabolic alkalosis (urine chloride < 25 mEq/L)
Chloride-resistant metabolic alkalosis (urine chloride > 40 mEq/L)

Respiratory disorderstoggle arrow icon

Respiratory acidosis

Etiology of respiratory acidosis [1]
Mechanism Causes
Acute respiratory acidosis
Chronic respiratory acidosis

Respiratory alkalosis

Gastrointestinal disorderstoggle arrow icon

Acid-base disturbances associated with GI disorders [20][21]
GI disturbance Acid-base disturbance Cl- K+ Na+

Severe diarrhea or laxative use

Metabolic acidosis

Prolonged vomiting or nasogastric suctioning

Metabolic alkalosis

The loss of bicarbonate-rich fluid in severe diarrhea may cause non-anion gap metabolic acidosis.

Treatmenttoggle arrow icon

General considerations [2]

Respiratory acidosis

Respiratory alkalosis

Metabolic acidosis

Metabolic alkalosis

Referencestoggle arrow icon

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  2. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015
  3. Kraut JA, Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management. Nature Reviews Nephrology. 2010; 6 (5): p.274-285.doi: 10.1038/nrneph.2010.33 . | Open in Read by QxMD
  4. Jaber S, Paugam C, Futier E, et al. Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial. Lancet. 2018; 392 (10141): p.31-40.doi: 10.1016/s0140-6736(18)31080-8 . | Open in Read by QxMD
  5. Kasper DL, Hauser SL, Loscalzo J, Longo DL, Jameson JL, Fauci AS. Harrison's Principles of Internal Medicine Vol 1 20e. McGraw-Hill Education / Medical ; 2018
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  7. Walkey AJ, Farber HW, O’Donnell C, Cabral H, Eagan JS, Philippides GJ. The Accuracy of the Central Venous Blood Gas for Acid-Base Monitoring. J Intensive Care Med. 2009; 25 (2): p.104-110.doi: 10.1177/0885066609356164 . | Open in Read by QxMD
  8. Chong WH, Saha BK, Medarov BI. Comparing Central Venous Blood Gas to Arterial Blood Gas and Determining Its Utility in Critically Ill Patients: Narrative Review. Anesth Analg. 2021; 133 (2): p.374-378.doi: 10.1213/ane.0000000000005501 . | Open in Read by QxMD
  9. Marano M. Evaluation of the expected ventilatory response to metabolic acidosis in chronic hemodialysis patients. Hemodial Int. 2017; 22 (2): p.180-183.doi: 10.1111/hdi.12602 . | Open in Read by QxMD
  10. Adrogué HJ, Madias NE. Secondary Responses to Altered Acid-Base Status: The Rules of Engagement. J Am Soc Nephrol. 2010; 21 (6): p.920-923.doi: 10.1681/asn.2009121211 . | Open in Read by QxMD
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  15. Halperin ML, Margolis BL, Robinson LA, Halperin RM, West ML, Bear RA. The urine osmolal gap: a clue to estimate urine ammonium in "hybrid" types of metabolic acidosis.. Clin Invest Med. 1988; 11 (3): p.198-202.
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