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:
- 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.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, 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
- (Increased oxygen extraction)
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:
- Head injury (Raised ICP, closed head injury)
- Nerve dysfunction:
- Spinal cord injury
- NMJ dysfunction:
- Muscular dysfunction:
- Chest wall abnormalities:
- Ankylosing Spondylitis
- Pleural fibrosis
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
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
- 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 is due to impaired cardiac output resulting in impaired oxygen delivery
- 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
- 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
- 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
- West J. Respiratory Physiology: The Essentials. 9th Edition. Lippincott Williams and Wilkins. 2011.
- Barrett KE, Barman SM, Boitano S, Brooks HL. Ganong's Review of Medical Physiology. 24th Ed. McGraw Hill. 2012.
- CICM July/September 2007
- ICU Basic Book.