LF129 17: Respiratory Control (FLAG Mechanism)

Respiratory Physiology 1

Introduction to Respiration

• External Respiration: Exchange of oxygen and carbon dioxide between an organism and its external environment.
• Breathing: Muscle contraction/relaxation to move air in and out of the lungs.
• Ventilation: Movement of air from outside to inside the body for gas exchange between air in the lungs and blood in capillaries within the alveoli.
• Ventilation and breathing are different aspects of external respiration.

Central Control of Breathing

• Three aspects to central control:
  • Voluntary/behavioral
  • Reflex/automatic
  • Emotional
  • Respiratory muscles

Reflexive/Automatic Control

• Generates respiratory rhythm.
• Inspiratory Rhythm: Generated by the preBötzinger Complex (preBötC).
• Expiratory Rhythm: Generated by the parafacial respiratory group (FRG).
• Ventral respiratory column coordinates reflex/automatic control.

Volitional Control

• Voluntary control of breathing patterns respiration.
• Originates in the motor cortex.
• Motor cortex neurons that modulate breathing synapse in the pons.
• Human respiratory system has remarkable voluntary control.
  • Static apnea world records:
    • Branko Petrović: 11.54 mins
    • Budimir Šobat: 24.33 mins
  • Pete Reed: 11.68 L lung capacity
  • Herbert Nitsch: Free diving world record: 214 m
• Voluntary control is limited by stimuli such as $PCO_2$ or $H+$, leading to the breaking point.

Emotional Control

• Emotional control of breathing can override respiratory patterning.
• Still occurs in locked-in syndrome.
• Arises through corticospinal projections, involving the sensorimotor cortex, thalamus, basal ganglia, spinal cord, brainstem, and cerebellum.
• Emotional control overrides breathing at the final point of output, involving the limbic system and motor cortex.

Feedback Mechanisms in Breathing

• Breathing is patterned via feedback mechanisms.
• Involves respiratory centres, pulmonary stretch receptors, and chemo-receptors.

Chemical Factors Regulating Breathing

• Arterial $CO<em>2$ ($PaCO</em>2$) is the major chemical factor regulating minute breathing.
• The ability of arterial $PCO_2$ to control breathing is largely due to the associated change in $[H^+]$.
• $CO_2$ is detected directly by both central and peripheral chemoreceptors.
• Even small increases in inhaled $CO_2$ stimulate breathing.
  • A 10% rise in $CO_2$ gives rise to a 100% increase in breathing.
  • A 20% rise in $CO_2$ more than trebles breathing.
• Hypercapnia (excess carbon dioxide) is a potent regulator of breathing.
• Arterial $PO_2$ has to fall to about half normal before breathing is stimulated.
  • 35% drop in $O_2$ gives rise to a 20% increase in breathing.
  • A 55% drop in $O_2$ is required for breathing to double.
• Hypoxia modulates breathing to a lesser degree than hypercapnia.

Chemoreceptors

• Peripheral Chemoreceptors: Detect alterations in blood gases, predominantly oxygen.
  • Carotid bodies: Located close to the bifurcation of the common carotid arteries in the neck.
  • Aortic bodies: Located close to the aortic arch.
  • Respond to changes in arterial blood:
    • Decreased $PO_2$ (hypoxia)
    • Increased $PCO_2$ (hypercapnia)
    • Increased $[H^+]$ (acidosis)
  • 80% of $O<em>2$ detection and 20% of $CO</em>2$ detection.
• Central Chemoreceptors: Mainly located in the medulla oblongata.
  • Respond to changes in cerebrospinal fluid.
  • Stimulated by increased $PCO_2$ or associated changes in $[H^+]$/pH.
  • 70% of $CO<em>2$ detection and 30% of $O</em>2$ detection.
  • $CA$ = carbonic anhydrase

Medullary Nuclei

Blood gas regulation involves many medullary nuclei:

• $PiCo$
• $Glia$ - $O<em>2$, $CO</em>2$
• $cPPy$ - $CO_2$ in adult
• $Raphe$ - $CO_2$ after P12
• $RTN$ - $CO_2$ at birth - Becomes integrator with age

Peripheral Integration

• Blood gas regulation requires peripheral integration.
• $Carotid$ $bodies$ - 80% $O<em>2$ - 20% $CO</em>2$
• $Nucleus$ $Tractus$ $Solitarius$ - $O<em>2$, $CO</em>2$

Integration from Higher Brain Areas

Blood gas regulation requires integration from higher brain areas, including:

• Amygdala (fear response to $CO_2$)
• Parabrachial ($O_2$)
• Locus Coeruleus ($CO_2$)
• Baro-receptors
• Blood gases and blood pressures must be regulated together.

Pulmonary Stretch Receptors

• Protect the lungs from:
  • $CO_2$ excess (hypercapnia)
  • $O_2$ lack (hypoxia)
• Slowly Adapting Pulmonary Stretch Receptors: Monitor lung inflation.
  • Located in smooth muscles of bronchi and trachea.
  • Stimulated by stretch.
  • Signal lung volume to the brain.
  • Inhibit inspiration and lengthen expiration (Hering-Breuer inflation reflex).
  • Regulate respiratory rhythm (e.g., exercise and sleep in neonates).
• Rapidly Adapting Pulmonary Stretch Receptors: Monitor irritants.
  • Located in epithelial cells in the larynx, trachea, and airways.
  • Respond to mechanical stress: large inflation/deflation.
  • Respond to the chemical environment of the lung: noxious gases, dust, cold, histamine.
  • Constrict the airway & promote rapid shallow breathing.
  • Responsible for the “gasping inspirations of the newborn”.
  • Promote cough in the trachea and larynx.
  • Promote sighing due to gradual collapse of lungs (atelectasis): ~5 minutes.

Sighing

• The control circuit for sighing is located in the RTN and preBötC.
  • $PBN$
  • $Integration$ $neurons$
  • $GRP$
  • $RTN$ $neurons$ ($\approx 30$)
  • $NMB$ $neurons$ ($\approx 200$)
  • $Sigh$
  • $2nd$
  • $NTS$
  • $preBotC$
  • $Sigh$-$activation$ $neurons$
  • $GRPR$ $neurons$ ($\approx 110$)
  • $NMBR$ $neurons$ ($\approx 40$)
  • $NMBR/GRPR$ $neurons$ ($\\approx 50$)
  • $Eupnea$
  • $1st$

Lung Compliance

• Change in lung volume produced by changes in transpulmonary pressure ($Ptp$).
• Compliance: Ability to expand lungs at any given change in ($Ptp$).
• There are two major determinants of lung compliance:
  1. “Stretchability” of tissues.
  2. Surface tension within alveoli.
• Lungs require compliance so that they may inflate and deflate.

Pulmonary Surfactant

• Surface tension within alveoli is lowered by pulmonary surfactant.
• The surface of alveoli is moist.
• Surface tension at the air-water interface resists stretching.
• Pulmonary surfactant lowers surface tension and increases compliance.
• Released from type II alveolar cells during sighing.
  • A mixture of phospholipids and protein.
  • Makes lungs easier to expand.
  • Secreted by type II alveolar cells.
  • Sighing increases secretion (by stretching the type II cells).
• Production in fetal lung in late gestation.
• Deficiency in premature babies causes respiratory distress syndrome of the newborn.

Protective Reflexes

• Coughs and sneezes are protective reflexes.
• Responses that protect the respiratory system from irritants.
• Sneeze Reflex: Due to receptors in epithelial cells of the nose or pharynx.
  • Air speed of 160 km·h-1
• Cough Reflex: Due to receptors in epithelial cells of the upper airway.
  • Air speed of 960 km·h-1

Summary of Respiratory Control

• Respiratory control
  • Reflexive
  • Volitional
  • Emotional
• Respiratory reflex
  • Chemoreception
  • Stretch receptors
  • Protective reflexes