Control of Breathing Study Notes

CHAPTER 4: CONTROL OF BREATHING

KEY POINTS

• Respiratory Centre in the Medulla
  • Generates the respiratory rhythm using an oscillating network of groups of interconnecting neurones.
• Influence of the Central Nervous System
  • Numerous diverse areas influence respiratory control, which are coordinated by the pons.
• Receptors and Reflex Actions
  • Irritant and stretch receptors in the lungs and diaphragm participate in reflex actions influencing respiratory activity.
• Central Chemoreceptors
  • Respond to pH changes due to variations in carbon dioxide partial pressure, rapidly increasing ventilation in response to elevated arterial $PCO_2$.
• Peripheral Chemoreceptors
  • Located predominantly in the carotid body, they increase ventilation in response to reduced arterial $PO_2$.

THE CONTROL SYSTEM OF BREATHING

• The control system is complex and automatically adapts to the changing demands of various physiological activities, including:
  • Posture
  • Speech
  • Voluntary movement
  • Exercise
  • Other circumstances altering respiratory requirements or influencing respiratory muscle performance.

THE ORIGIN OF THE RESPIRATORY RHYTHM

• Brainstem Involvement

  • Removal or stimulation of specific brainstem areas in animals has been studied to determine respiratory function.
  • Recent imaging techniques confirm the localization of respiratory regions in humans.

• Anatomical Location of the Respiratory Centre

  1. Medulla
  • Dorsal respiratory group (DRG)
    • Associated with nucleus tractus solitarius; influenced by visceral afferents from cranial nerves IX and X.
    • Contains inspiratory neurones with upper motor neurons projecting to contralateral inspiratory anterior horn cells, primarily concerned with timing the respiratory cycle.
  • Ventral respiratory group (VRG)
    • Comprises a column of respiratory neurons including:
      • Caudal Ventral Respiratory Group: Mostly expiratory neurons, directs upper motor neurons to contralateral expiratory muscles.
      • Rostral Ventral Respiratory Group: Dominated by nucleus ambiguous; involved in airway dilation in the larynx, pharynx, and tongue.
    • Pre-Bötzinger Complex: The presumed anatomical location of the central pattern generator (CPG).
    • Bötzinger Complex: Located within the nucleus retro-facialis, primarily responsible for widespread expiratory functions.

• Dorsal and Ventral Respiratory Group Structure

  • Details illustrated in Fig. 4.2, showing areas involved with expiratory (in blue) and inspiratory (in brown) activities.
  • Fibres that decussate are shown crossing the midline, with broken lines indicating pathways that inhibit inspiratory neurons.

CENTRAL PATTERN GENERATOR (CPG)

• Group-Pacemaker System
  • No single neurone acts as the pacemaker for breathing.
  • Breathing is coordinated by a group-pacemaker system involving groups of neurons generating regular bursts of activity.
  • Involves a complex interaction of at least six groups of neurons, identifiable firing patterns concentrated around the pre-Bötzinger complex:
  • Inspiratory Neurones
  • Inspiratory Augmenting Neurones (Iaug)
  • Late Inspiratory Interneurones: Possessing putative 'off-switch' functions.
  • Early Expiratory Decrementing Neurones
  • Expiratory Augmenting Neurones
  • Late Expiratory Preinspiratory Neurones

RESPIRATORY CYCLE

• Inspiratory Phase
  • Initiates suddenly, leading to a ramp increase in Iaug neurones and motor discharge to inspiratory muscles.
  • Pharyngeal dilator muscles contract before inspiration, likely by activation of late expiratory (preinspiratory) neurons.
• Postinspiratory/Expiratory Phase I
  • Characterized by declining Iaug neurone activity and motor discharge to inspiratory muscles, resulting in passive expiration and initial gas flow rate braking via the larynx.
• Expiratory Phase II
  • Inspiratory muscles become silent, with the activation of expiratory augmenting neurones leading to increased expiratory muscle activity.
• Illustrative firing patterns of respiratory neurone groups depicted in Fig. 4.3, differentiating phases of expiration (passive Phase I and active Phase II).

CELLULAR MECHANISMS OF CENTRAL PATTERN GENERATION

• Neurotransmitter Roles

  • Excitatory and inhibitory neurotransmitters considerably affect respiratory control via:
  • Direct activation of other neurons.
  • Modulation of spontaneous activity via effects on membrane ion channels.

• Types of Neurotransmitters

  • Excitatory Amino Acids: (e.g., glutamate) activating multiple receptors.
  • Inhibitory Neurotransmitters: (e.g., glycine and GABA) influencing neuron hyperpolarization and activity inhibition.

EFFERENT PATHWAYS FROM THE RESPIRATORY CENTRE

• Three groups of upper motor neurons converge on the anterior horn cells:
  • From the dorsal and ventral respiratory groups, responsible for both inspiratory and expiratory outputs.
  • Involvement in voluntary control (e.g., speech) and involuntary, non-rhythmic control (e.g., swallowing, coughing, hiccups).

CNS CONNECTIONS TO THE RESPIRATORY CENTRE

• The Pons

  • Contains pontine neurons that synchronize with the different phases of respiration, termed the pontine respiratory group (PRG).
  • Three neuron types detected in the PRG:
  • Inspiratory
  • Expiratory
  • Phase spanning
  • Coordinated respiratory effects encompass inputs from the hypothalamus, cortex, and nucleus tractus solitarius, integrating diverse CNS activities.

• Cerebral Cortex Influence

  • Voluntary interruption and alteration of breathing patterns, regulated by arterial blood gas tension changes.
  • Provides control over speech, singing, sniffing, coughing, and tests of ventilatory function.
  • Notably, while reading aloud, correct respiratory boundaries are achieved 88% of the time compared to only 63% during spontaneous speech.

• Ondine’s Curse (Primary Alveolar Hypoventilation Syndrome)

  • Identified by Severinghaus and Mitchell (1962); patients exhibit prolonged apnoea while awake but breathe on command.
  • Conditions often related to poliomyelitis or stroke; addresses congenital central hypoventilation syndrome resulting in apnoea and hypoventilation during sleep linked to the PHOX2B gene defect.

PERIPHERAL INPUT TO THE RESPIRATORY CENTRE AND NONCHEMICAL REFLEXES

• Reflexes from the Upper Respiratory Tract

  • Nose: Water and irritants (e.g., ammonia) can induce apnoea through the diving reflex; sneezing initiates involuntary reflexes.
  • Pharynx: Mechanoreceptors in the pharynx activate the pharyngeal dilator muscles, influencing airway dynamics.
  • Larynx: Reflex actions include increasing activity of pharyngeal dilator muscles and reactions to irritants leading to cough and bronchoconstriction.

• Cough Reflex

  • Phases:
  1. Inspiratory phase
  2. Compressive phase
  3. Expulsive phase
  • Distinct from expiration reflex, which prevents aspiration without an inspiratory phase.

• Reflexes from the Lung

  • Pulmonary Stretch Receptors: Types sensitive to inflation/deflation and mostly signal through vagus nerves.

  • Slowly Adapting Stretch Receptors (SARs): Maintain firing rate during sustained lung inflation.

  • Rapidly Adapting Stretch Receptors (RARs): Located in mucosal layers, respond to tidal volume changes and irritants.

  • Hering-Breuer Reflexes:

  • Inflation reflex and deflation reflex respond to changes in lung transmural pressure.

• Head’s Paradoxical Reflex: A counter-reaction to the inflation reflex indicating the complexity of lung reflex management.

THE INFLUENCE OF CARBON DIOXIDE ON RESPIRATORY CONTROL

• Both central and peripheral chemoreceptors are critical for detecting carbon dioxide's effects on breathing.
• Central Chemoreceptors Localization: Primarily on the ventrolateral surface of the medulla, at the retrotrapezoid nucleus (RTN).
• Mechanism of Action:
  • Elevated arterial $PCO_2$ results in increased levels in extracellular fluid and cerebrospinal fluid (CSF), leading to decreased CSF pH, triggering chemoreceptive responses.
• Compensatory Bicarbonate Shift in CSF: Over time, abnormal $PCO_2$ levels lead to buffering adjustments in CSF bicarbonate concentration, influencing pH.

THE INFLUENCE OF OXYGEN ON RESPIRATORY CONTROL

• Initial belief suggested hypoxia directly stimulated respiration; later studies indicated a chemoreceptor function in the carotid body.

• Peripheral Chemoreceptor Function:

  • Quick responders to arterial blood changes, particularly drops in $PaO_2$ and increases in $PaCO_2$ or H+. Ventilation increases in response to activation of these chemoreceptors.

• Peripheral chemoreceptors located near common carotid artery bifurcations, connecting rapid function to clinical scenarios in chronic hypoxia, with anatomical adaptations noted (e.g. hyperplasia in chronic conditions).

• Mechanism of Action: Involves oxygen-sensitive potassium channels within type I cells (glomus cells), modulating the membrane potential to trigger transmitter release and physiological responses.

TIME COURSE OF RESPIRATORY RESPONSES

• Hypoxia Response Phases: Notably triphasic with immediate increase in ventilation, followed by a decline and eventual plateau at elevated ventilation levels.
• Central Respiratory Depression: Hypoxia can significantly reduce the activity of central respiratory neurons, leading to potential apnoea due to medullary oxygen deficiency.

INTEGRATION OF CHEMICAL CONTROL OF BREATHING

• Respiratory responses integrate various stimuli (changes in $PCO_2$, $PO_2$, pH) for a coordinated respiratory behaviour.

METHODS FOR ASSESSMENT OF BREATHING CONTROL

• Various methods assess sensitivity to carbon dioxide and hypoxia,
  • Including rebreathing techniques and steady-state assessments.

END OF RESPIRATORY CONTROL NOTES