Explain the physiological effects of hyperoxia, hypoxaemia, hypercapnia, hypocapnia, and carbon monoxide poisoning.

  • Hypoxaemia is a low partial pressure of oxygen in blood
  • Hypoxia is an oxygen deficiency at the tissues, due to:
    • Impaired oxygen delivery
    • Impaired oxygen extraction

Oxygen delivery is given by the equation:
, where:

  • 1.34 is Hüfner's constant
    This is the oxygen carrying capacity of haemoglobin, in ml.g-1 (of Hb).
    • The theoretical maximum is 1.39
    • In vivo it is 1.34 due to the effect of carboxyhaemoglobin and methaemoglobin compounds, which limit O2 binding
  • 0.03 is the solubility coefficient of O2 in water at 37ºC, in mls.L-1.mmHg-1
    Can also be expressed as 0.003 mls.dL-1.mmHg-1 (mls per deciliter per mmHg). Different texts use different values, depending on whether haemoglobin is reported in g.L-1 or g.100ml-1.

Classifications and Causes of Hypoxia

Hypoxia can be categorised into four types:

  • Hypoxic hypoxia
  • Anaemic hypoxia
  • Ischaemic hypoxia
  • Histotoxic hypoxia

Hypoxic Hypoxia

Hypoxic hypoxia, or hypoxaemia, is hypoxia due to low PaO2 (and therefore low SpO2), typically defined as a PaO2<60.

Causes of hypoxaemia can be further classified based on their A-a gradient:

  • Causes of hypoxaemia with a normal A-a gradient:
    • Low PiO2
    • Decreased alveolar ventilation
  • Causes of hypoxaemia with a raised A-a gradient:
    • Diffusion limitation
    • Shunt
    • (Increased oxygen extraction)

Low FiO2

Hypoxaemia occurs at high altitudes when the PO2 is decreased.

Decreased alveolar ventilation

A fall in alveolar ventilation ( ) causes a rise in PACO2, and therefore decreases PAO2. Decreased VA can occur with:

  • Respiratory centre depression:
    • Drugs
    • Head injury (Raised ICP, closed head injury)
    • Encephalopathy
    • Fatigue
  • Nerve dysfunction:
    • Spinal cord injury
    • GBS
    • MND
  • NMJ dysfunction:
    • Paralysis
    • MG
  • Muscular dysfunction:
    • Myopathy
    • Fatigue
    • Malnutrition
    • Dystrophy
  • Chest wall abnormalities:
    • Kyphoscoliosis
    • Ankylosing Spondylitis
    • Pleural fibrosis

Diffusion Limitation

Impaired diffusion of O2 across the membrane results in a lowered PaO2. Diffusion limitation occurs due to:

  • Decreased alveolar surface area
  • Increased alveolar capillary barrier thickness
    • Pulmonary fibrosis
    • ARDS


Shunt occurs when blood reaches the systemic circulation without being oxygenated via passage through the lung. As the alveolus is perfused but not ventilated, thus the V/Q ratio is 0.

  • Administration of 100% O2 has less effect on PaO2 as shunt fraction increases
    • Oxygen content of shunted alveoli is identical to mixed venous content
    • Oxygen content of non-shunted alveoli does not increase appreciably at high partial partial pressures as haemoglobin is already fully saturated

Shunt physiology is explored in more detail under shunt.

Increased Oxygen Extraction

  • Increased oxygen extraction (VO2) will not typically cause hypoxia
  • This is because:
    • Normal VO2 is 250ml.min-1
    • Normal DO2 is 1L.min-1
    • Maximal oxygen extraction ratio is ~70% (though it varies between organs)
      Therefore VO2 can increase until it reaches 70% of the DO2, a point called critical DO2.
  • However, it may worsen hypoxia in the presence of a supply-side (DO2) pathology

Anaemic Hypoxia

  • Impaired oxygen delivery due to low Hb
  • Typically asymptomatic at rest but limits exercise tolerance

  • Compensation occurs by increasing levels of 2,3-DPG, causing a right-shift in the Hb-O2 dissociation curve to favour oxygen off-loading at tissues

Carbon Monoxide Poisoning

  • CO poisoning is classified as a subset of anaemic hypoxia as carboxyhaemoglobin reduces the effective amount of haemoglobin in solution
  • CO has 210 times the affinity for Hb than O2
    • CO rapidly displaces O2 from Hb and is liberated slowly
  • CO poisoning causes headache and nausea, but no increased respiratory drive since the PaO2 is unchanged

Ischaemic Hypoxia

  • Ischaemic hypoxia is due to impaired cardiac output resulting in impaired oxygen delivery

Histotoxic Hypoxia

  • Histotoxic hypoxia is due to impaired tissue oxidative processes, preventing utilisation of delivered oxygen
  • Most common cause of histotoxic hypoxia is cyanide poisoning, which inhibits cytochrome oxidase and prevents oxidative phosphorylation
  • Managed by using methylene blue or nitrites, which form methaemoglobin, in turn reacting with cyanide to form the non-toxic cyanmethaemoglobin

Effects of Hypoxia

  • With a normal PaCO2, PaO2 must fall to 50mmHg before an increase in ventilation occurs
  • With a rising PaCO2, a fall in PaO2 below 100mmHg will stimulate ventilation via action on carotid and aortic body chemoreceptors
    • The effects of each stimuli are synergistic, and greater than what is seen with either effect alone
  • Prolonged hypoxaemia will also lead to cerebral acidosis (via anaerobic metabolism), which will stimulate central pH receptors and stimulate ventilation

Acid-Base Changes

  • Hypoxia results in both fixed and volatile acid-base disturbances
  • Anaerobic metabolism results in lactate production
  • Production of fixed acid results in a base deficit, and a low bicarbonate
  • Hypoxia and metabolic acidosis stimulate ventilation and hypocarbia

CO2 retention

  • In chronic hypercarbia the CSF pH normalises (as bicarbonate is secreted into CSF), with a raised CO2
  • Fall in PaO2 becomes the predominant stimulus for ventilation


  1. West J. Respiratory Physiology: The Essentials. 9th Edition. Lippincott Williams and Wilkins. 2011.
  2. Barrett KE, Barman SM, Boitano S, Brooks HL. Ganong's Review of Medical Physiology. 24th Ed. McGraw Hill. 2012.
  3. CICM July/September 2007
  4. ICU Basic Book.
Last updated 2021-10-06

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