Disorders of acid-base balance can lead to severe complications in many disease states.¹ Arterial blood pH is normally closely regulated to between 7.35 and 7.45.²

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.

Diagnosing acid-base balance disorders (investigations)

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 acidosi metabolica. Otherwise the change is compensatory (that is, normal or raised in respiratory acidosis; normal or decreased in respiratory alkalosis).

• 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).

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).

• Increased anion gap:

  • Acidosi lattica: 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):

  • Acidosi tubulare renale.

  • Diarrea.

  • Morbo di Addison.

  • Pancreatic fistulae.

  • Drugs or toxins: acetazolamide, ammonium chloride.

Questi includono:

• Vomito.

• Ipokaliemia - eg, diuretics. See also the separate Hypokalaemic alkalosis articolo.

• Excessive alkali drugs, such as for acid dyspepsia.

• Ustioni.

• Acute:

  • Depression of the central respiratory centre by cerebrovascular disease or drugs.

  • Inability to ventilate adequately due to neuromuscular disease - eg, miastenia grave, amyotrophic lateral sclerosis, Sindrome di Guillain-Barré, muscular dystrophy.

  • Airway obstruction related to asma oppure exacerbation of chronic obstructive pulmonary disease (COPD).

• Chronic:

  • Chronic respiratory acidosis may be secondary to many disorders - eg, BPCO, obesity hypoventilation syndrome (Pickwickian syndrome), neuromuscular disorders and restrictive ventilatory defects such as interstitial fibrosis or thoracic deformities.

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.