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Acid-base balance

Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find the Arterial blood gases article more useful, or one of our other health articles.

Disorders of acid-base balance can lead to severe complications in many disease states1. Arterial blood pH is normally closely regulated to between 7.35 and 7.452.

Maintaining the pH within these limits is achieved by bicarbonate, other buffers, the lungs and the kidneys. Primary changes in bicarbonate are metabolic and primary changes in carbon dioxide are respiratory.

In the absence of any significant respiratory disease or hyperventilation, the primary cause is much more likely to be metabolic. However, central hypoventilation (eg, caused by CNS disturbance such as stroke, head injury or brain tumour) causes respiratory acidosis. In general, the kidneys compensate for respiratory causes and the lungs compensate for metabolic causes.

Therefore, hyperventilation may be a cause of respiratory alkalosis or a compensatory mechanism for metabolic acidosis. Deep sighing respiration (Kussmaul breathing) is a common feature of acidosis (hyperventilation in an attempt to remove carbon dioxide) but may take some hours to appear.

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Analysis of arterial blood gases provides:

  • pH: determines whether there is an overall acidosis or alkalosis. Venous pH is in practice as reliable as arterial pH.

  • Carbon dioxide partial pressure (PaCO2): if raised with acidosis then the acidosis is respiratory. If decreased with alkalosis then the alkalosis is respiratory. Otherwise any change is compensatory.

  • Standard bicarbonate (SBCe): analysis of blood gases provides a bicarbonate level which is calculated from the PaCO2 using the Henderson-Hasselbalch equation.

  • Bicarbonate (HCO3): increased with metabolic alkalosis and decreased in metabolic acidosis. Otherwise the change is compensatory (ie normal or raised in respiratory acidosis; normal or decreased in respiratory alkalosis).

Assessment of acid-base imbalance

  • Check pH: if below 7.35 then it is an acidosis; if above 7.45 then it is an alkalosis.

  • Check PaCO2: if it has moved in the same direction as pH then the primary cause is metabolic; if it has moved in the opposite direction, the primary cause is respiratory.

  • If there is a respiratory cause then changes in pH and HCO3 should be as follows:

    • If acute acidosis: pH falls by 0.08 and HCO3 rises by 1 mmol/L for each 10 mm Hg PaCO2 above 40 mm Hg.

    • If chronic acidosis: pH falls by 0.03 and HCO3 rises by 2-4 mmol/L for each 10 mm Hg of PaCO2 above 40 mm Hg.

    • For respiratory alkalosis, the opposite directions are present for all changes.

  • If there is a metabolic acidosis then calculate the expected PaCO2 and compare to measured value to see if there is also a respiratory component. Expected PaCO2 = (1.5 x [HCO3] + 8) +/- 2. A lower than expected PaCO2 indicates a superimposed respiratory alkalosis, and a higher than expected PaCO2 indicates a respiratory acidosis.

  • If metabolic alkalosis: calculate the expected PaCO2 and compare to measured value to see if there is also a respiratory component. Expected PaCO2 = (0.9 x [HCO3] + 9) +/- 2.

  • Also work out anion gap (see below).

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Anion gap3

In plasma, the sum of the cations (sodium plus potassium) is normally greater than that of the anions (chloride plus bicarbonate) by approximately 14 mmol/L. This is known as the anion gap. The normal reference range for the anion gap is 10-20 mmol/L.

  • The anion gap exists because there are more unmeasured anions (mostly albumin, but others include lactate and sulfate) than cations (includes calcium and magnesium).

  • Metabolic acidosis is generally divided into those with high and those with normal anion gap.

  • High chloride (Cl-) associated with metabolic acidosis is most often due to compensation for gastrointestinal bicarbonate loss (eg, severe/prolonged diarrhoea).

Causes of metabolic acidosis

  • Increased anion gap:

    • Lactic acidosis: shock, infection, hypoxia.

    • Urate (renal failure).

    • Ketones (diabetes mellitus, alcohol).

    • Drugs or toxins: salicylates, metformin, ethylene glycol, methanol, cyanide.

  • Normal anion gap (due to loss of bicarbonate or ingestion hydrogen ions):

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Causes of metabolic alkalosis

These include:

Causes of respiratory acidosis

Causes of respiratory alkalosis

Respiratory alkalosis results from hyperventilation - eg, anxiety, stroke, meningitis, altitude, pregnancy (see the separate Hyperventilation article).


Treatment is of the underlying condition.


  • Cardiovascular effects: acidosis reduces cardiac contractility and both acidosis and alkalosis predispose to arrhythmias.

  • Nervous system effects: severe acidosis often causes impaired consciousness, ranging from mild drowsiness to coma.

Further reading and references

  • Singh V, Khatana S, Gupta P; Blood gas analysis for bedside diagnosis. Natl J Maxillofac Surg. 2013 Jul;4(2):136-141.
  • Carmody JB, Norwood VF; Paediatric acid-base disorders: A case-based review of procedures and pitfalls. Paediatr Child Health. 2013 Jan;18(1):29-32.
  • Lee Hamm L, Hering-Smith KS, Nakhoul NL; Acid-base and potassium homeostasis. Semin Nephrol. 2013 May;33(3):257-64. doi: 10.1016/j.semnephrol.2013.04.006.
  • Curthoys NP, Moe OW; Proximal Tubule Function and Response to Acidosis. Clin J Am Soc Nephrol. 2014 May 1.
  • Koeppen BM; The kidney and acid-base regulation. Adv Physiol Educ. 2009 Dec;33(4):275-81. doi: 10.1152/advan.00054.2009.
  • Seifter JL, Chang HY; Disorders of Acid-Base Balance: New Perspectives. Kidney Dis (Basel). 2017 Jan;2(4):170-186. doi: 10.1159/000453028. Epub 2016 Dec 10.
  • Quade BN, Parker MD, Occhipinti R; The therapeutic importance of acid-base balance. Biochem Pharmacol. 2021 Jan;183:114278. doi: 10.1016/j.bcp.2020.114278. Epub 2020 Oct 9.
  1. Sood P, Paul G, Puri S; Interpretation of arterial blood gas. Indian J Crit Care Med. 2010 Apr;14(2):57-64. doi: 10.4103/0972-5229.68215.
  2. Hopkins E, Sanvictores T, Sharma S; Physiology, Acid Base Balance. StatPearls, 2020.
  3. Hamilton PK, Morgan NA, Connolly GM, et al; Understanding Acid-Base Disorders. Ulster Med J. 2017 Sep;86(3):161-166. Epub 2017 Sep 12.

Article history

The information on this page is written and peer reviewed by qualified clinicians.

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