Control of Breathing

Master answer

Role of CO2 in control of alveolar ventilation

Sensors

Central chemoreceptors
Located in the medulla, just below the central surface
Stimulated by increased pH of CSF. Not stimulated by low PO2
CO2 crosses the blood brain barrier easily
-> combines with water to make carbonic acid
-> dissociates to produce hydrogen ions lowering pH

Peripheral chemoreceptors
Carotid bodies at bifurcation of common carotid artery (supplied by glossopharyngeal nerve)
Aortic bodies (supplied by the vagus nerve)
Sense changes in PO2, PCO2 and pH (not in aortic bodies)
Globus cells release neurotransmitters (dopamine, noradrenaline, acetylcholine)
-> stimulates afferent nerves -> medulla -> increased ventilation

Lung receptors, Baroreceptors
No role of CO2

Central input

There is input from the hypothalamus and cortex, with the ability of the cortex to override the medulla and bring ventilation under voluntary control

Controller

• Medullary respiratory centre
  • Dorsal group
    • Part of nucleus tractus solitarius
    • Timing of ventilation
  • Ventral group
    • In nucleus ambiguous and nucleus retroambigualis
    • Controls inspiration
  • Botzinger complex
    • Rostral to nucleus ambuguus
    • Controls expiration (inactive at quiet breathing)
• Inspiratory phase:
  • Gradual ramping up of nerve activity – ↑muscle contraction
• Expiratory phase I:
  • Gradual reduction of nerve activity – ↓muscle contraction
• Expiratory phase II:
  • Inspiratory muscles inactive
  • If increased respiratory drive, expiratory muscles are activated

Effectors

Mainly diaphragm (via phrenic nerves)
Also intercostal muscles and abdominal wall (forced expiration)

Effect of CO2 on Alveolar Ventilation

• ↑ CO2
  • ↑ RR + ↑ Depth of breathing → Steady state hyperventilation in few mins
  • Linear response in usual range ( MV ↑ 2L/min for 1mmHg rise on PaCO2)
  • Max Ventilatory stimulation at ~100mmHg → Respiratory fatigue, CO2 narcosis
• ↓ CO2
  • ↓ Alveolar ventilation
  • Once PaCO2 <30mmHg
    • Some reduce ventilation to point of apnoea
    • Some continue to breath (Due to cortical control of respiration especially when awake)
• Responses may be blunted by partial neuromuscular blockade, Restrictive or obstructive lung disease, airway obstruction
• Prolonged periods of CO2 retention:
  • → Active secretion of bicarb into CSF → CSF pH normalized → central chemoreceptor stimulation ceases
  • → renal reabsorption of bicarb → normalizes arterial pH normalized → ↓ peripheral chemoreceptor stimulation

References: Nunn’s Applied Respiratory Physiology, Pulmonary Physiology.

Mooney / JC 2019

Answer by JC, Mooney