Arterial blood pH is normally closely regulated to between 7.35 and 7.45. 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 it can be assumed that the primary cause is metabolic.
• 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.

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 metabolic acidosis. Otherwise the change is compensatory (i.e. normal or raised in respiratory acidosis; normal or decreased in respiratory alkalosis).

Assessment of acid-base imbalance

• Check pH: if below 7.35 then is an acidosis; if below 7.45 then 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 is 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).

Anion gap

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 8-16 mmol/L when not including potassium in the equation and 10-20 mmol/L when including potassium.

• 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 usually due to impaired renal handling of acid, e.g. renal tubular acidosis.

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):
  • Renal tubular acidosis.
  • Diarrhoea.
  • Addison's disease.
  • Pancreatic fistulae.
  • Drugs or toxins: acetazolamide, ammonium chloride.

Causes of metabolic alkalosis

These include:

• Vomiting.
• Hypokalaemia, e.g. diuretics.
• Excessive alkali drugs, such as for acid dyspepsia.
• Burns.

Causes of respiratory acidosis

• Acute:
  • Depression of the central respiratory centre by cerebrovascular disease or drugs.
  • Inability to ventilate adequately due to neuromuscular disease, e.g. myasthenia gravis, amyotrophic lateral sclerosis, Guillain-Barré syndrome, muscular dystrophy.
  • Airway obstruction related to asthma or exacerbation of chronic obstructive pulmonary disease (COPD).
• Chronic:
  • Chronic respiratory acidosis may be secondary to many disorders, e.g. COPD, obesity hypoventilation syndrome (Pickwickian syndrome), neuromuscular disorders and restrictive ventilatory defects such as interstitial fibrosis or thoracic deformities.

Causes of respiratory alkalosis

Respiratory alkalosis results from hyperventilation, e.g. anxiety, stroke, meningitis, altitude, pregnancy (see separate Hyperventilation article).

Management

Treatment is of the underlying condition.

Complications

• 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.

Internet and further reading

• Williams AJ; ABC of oxygen: assessing and interpreting arterial blood gases and acid-base balance. BMJ. 1998 Oct 31;317(7167):1213-6.
• Drage S, Wilkinson D; Acid-Base Balance: Pharmacology; Issue 13 (2001) Article 12.

Acknowledgements