Question 14

College Answer

A logical approach to answering this question included a definition of hypoxaemia and then a discussion of the sensors, integrators and effectors involved. It was expected that candidates would cover the peripheral chemoreceptor response (including the respiratory, cardiovascular and autonomic effects), time course of the ventilatory response, hypoxia-inducible factors, vascular effects (hypoxic vasoconstriction in the pulmonary circulation and vasodilatation in the systemic circulation) and metabolic changes (switch to anaerobic metabolism). No marks were awarded for discussing the causes of hypoxaemia. Many candidates incorrectly stated that hypoxaemia is detected by the central chemoreceptors.

Discussion

Definition of hypoxaemia

• Hypoxaemia is an abnormally low concentration of oxygen in arterial blood; whereas hypoxia is the condition of being deprived of adequate oxygen.  

Detection of hypoxaemia

• Sensors: peripheral chemoreceptors at the carotid glomus and in the aortic arch
• Afferents: vagus nerve and glossopharyngeal nerve
• Controller: central medullary and pontine respiratory control centres
• Efferents: phrenic nerve and spinal innervation of respiratory skeletal muscles
• Effectors: diaphragm, intercostal muscles, scalenes and abdominal muscles 

Response to hypoxaemia

• Ventilatory response
  • Decreasing PaO₂ causes an increase in minute ventilation.
  • The relationship between oxygen tension and minute volume can be described as a hyperbolic curve
  • The inflexion point for this relationship is approximately a PaO₂ of 50-60 mmHg; beyond this threshold value the minute volume increases steeply
• Cardiovascular effects of hypoxaemia 
  • Hypoxic vasoconstriction in the pulmonary circulation
  • Hypoxic vasodilatation in the systemic circulation
• Autonomic effects of hypoxaemia
  • Increased sympathetic and vagal tone, but the sympathetic increase dominates
  • Increased cardiac output and tachycardia are the net result
  • Hypoxic systemic vasodilation prevents hypertension
• Cellular effects of hypoxaemia
  • Absence of oxygen facilitates the switch to anaerobic metabolism of glucose
• Hypoxia-inducible factors
  • These are transcriptional activators which meidate adaptive responses to low oxygen availability (Semenza, 2012)
  • Their effects include:
    • Increased haemopoiesis
    • Decreased cell differentiation
    • Accelerated angiogenesis

Semenza, Gregg L. "Hypoxia-inducible factors in physiology and medicine." Cell 148.3 (2012): 399-408.

Ward, D. S., S. B. Karan, and J. J. Pandit. "Hypoxia: developments in basic science, physiology and clinical studies." Anaesthesia 66 (2011): 19-268.

Fukuda, Yasuichiro, et al. "Autonomic nerve and cardiovascular responses to changing blood oxygen and carbon dioxide levels in the rat." Journal of the autonomic nervous system 28.1 (1989): 61-74.