Chemoreceptors

• Importance of Chemoreceptors:

  • Control and modify ventilation on breath by breath basis
  • Feedback input to respiratory control centre → alter intrinsic respiratory pattern
  • To maintain PaCO2, PaO2 and pH within physiological limits regardless of activity
• 2 types of chemoreceptors:

  • peripheral chemoreceptors
  • central chemoreceptors
• Peripheral chemoreceptors:

  • Located aortic arch & carotid body
  • Sample surrounding arterial blood
  • Sensitive to arterial hypoxaemia – > when theres 40% reductions in PaO2 – PaO2 8 KPa or less
  • increase hydrogen ion content arterial blood
  • Weakly sensitive to PaCO2
• Central Chemoreceptors:

  • Located ventral surface of medulla bilaterally
  • Bathed in Cerebrospinal fluid
  • cerebrospinal fluid PCO2 = arterial PCO2 (same concentration)
  • Sensitive to arterial hypercapnia
  • Specifically increase Hydrogen ion concentration
  • Responsible for 70% of drive to breath
  • Central chemoreceptors have increase sensitivity to CO2 with mild hypoxia and acidosis
• Response of Central Chemoreceptors:

  • Central chemoreceptors feedback to respiratory control centre
  • respiratory control centre stimulate effectors
  • Increase rate and depth of ventilation
  • Until CO2 / pH levels back in normal range
  • Conversely when CO2 is low rate and depth of ventilation is reduced to allow
  • CO2 / pH to normalise
• CO2 Stimulation of Central Chemoreceptors:

  1. CO2 diffuses across blood brain barrier
  2. CO2 combines with H2O in cerebrospinal fluid
  3. This forms carbonic acid
  4. Carbonic acid disassociates to form bicarbonate and hydrogen ions
  5. CO2 + H2O -> H2CO3 -> HCO3 + H+
  6. H+ increases acidity, decreasing pH of cerebrospinal fluid
  7. decrease of pH of cerebrospinal fluid stimulates central chemoreceptors

  
• Additional Actions of Chemoreceptors

  • Stimulate sympathetic activity
  • Inhibit parasympathetic activity
  • Increase arterial blood pressure
• What happens when CO2 is chronically raised in a patient with COPD or Chronic Hypercapnia?

  1. CO2 + H2O -> H2CO3 -> HCO3 + H+
  2. Transport of HCO3 across blood brain barrier to “buffer” cerebrospinal fluid Hydrogen ions
  3. May take up to 3 days for full effect
  4. Effective buffering returns CSF pH to normal
  5. Reducing sensitivity of central chemoreceptors
  6. But arterial blood CO2 remains raised
  7. So blood pH remains acidotic
• If central chemoreceptors no longer sensitive to CO2 what is COPD/Chronic Hypercapnia patient’s drive to breathe?

  • Hypoxaemia sensed by peripheral chemoreceptors, that are sensitive when pao2 reaches 8 KPa or less, driving breathing
  • This is called Hypoxic Drive
• Why do patients with COPD retain CO2 ?

  • They have large V/Q mismatch and can’t maintain increased ventilation to excrete CO2
• What would happen if patient with COPD and hypercapnia is given high levels of therapeutic O2?

  • increased levels PaCO2, Secondary to:
  • Loss of hypoxic drive
  • Increased V/Q mismatch due to reversal HPVC
  • Haldane effect
• Loss of Hypoxic Drive:

  • COPD patients with chronic hypercapnia rely on peripheral chemoreceptors to sense arterial hypoxaemia
  • If patient given high dose O2, arterial hypoxaemia is reversed
  • Only remaining drive to breathe is removed
• Hypoxic Pulmonary Vasoconstriction

  • In respiratory disease areas of poor ventilation lead to decrease in gas exchange & hypoxia
  • When PaO2 falls to ~ 6 Kpa / SaO2 low 80 's hypoxia is sensed by receptors in arterioles
  • Arterioles passing through area of poor ventilation constrict to minimise V/Q mismatch
  • Blood flow is redirected to area with good ventilation to facilitate gas exchange
• Increased V/Q Mismatch:

  • COPD patients have areas of lung destruction with poor ventilation → hypoxia
  • V/Q mismatch
  • Compensatory HPVC occurs in those areas
  • If COPD patient given high dose O2, hypoxia in good lung tissue is reversed
  • Sensed by control centres so HPVC is also reversed
  • Leading to perfusion of non-ventilated lung and increased V/Q mismatch
• Haldane Effect:

  • Haemoglobin (Hb) has strong affinity for O2
  • O2 transported bound to Hb
  • When low O2 (e.g. COPD) CO2 binds to Hb
  • If give patient high dose O2, Hb brakes off from CO2 in preference to bind with O2
  • CO2 dissolves in plasma
  • Raising PaCO2
• Chemoreceptors send signals of low co2 to the diaphragm via the phrenic nerve