1. Ventral Respiratory Group (VRG)
    • Tlocated in the ventrolateral medulla
    • associated with the retrofacial nucleus (RFN), nucleus ambiguus (NA) and nucleus retroambigualis (NRA).
    • predominantly motor.
    • Many I and E neurons from the NRA cross the midline to provide rhythmical drive to the phrenic and thoracic motorneurons.
  2. Dorsal Respiratory Group (DRG)
    • form the ventrolateral nucleus of the tractus solitarius (vl-NTS) in the dorsomedial medulla.
    • They are predominantly sensory.
    • The tractus solitarius contains afferent fibers from chemoreceptors and mechanoreceptors.
  3. Pontine Respiratory Group (PRG)
    • lie in the dorsolateral pons in the nucleus parabrachialis medialis (NPBM) and Kölliker-Fusé nucleus (KF).
    • They have inspiratory, expiratory and I-E phase spanning activity.
    • The latter activity seems to be important in switching from inspiration to expiration and vice versa.
    • These functions were originally ascribed to the pneumotaxic center.
  4. Central Rhythm Generation
    Between the RFN and the remainder of the VRG is a cluster of respiratory neurons called the preBötzinger complex (preBötC) which is responsible for the maintenance of respiratory rhythmicity and its modulation by various inputs from receptor sites and other regions of the central nervous system
  5. Motorneuron Output
    • There are three types arising in the ventral horn of the spinal cord:
    • (1) Phrenic alpha-motorneurons which innervate the diaphragm arise at C3-C5 level.
    • (2) Thoracic motorneurons innervate the intercostal muscles. Some are active during inspiration, some during expiration.
    • (3) Abdominal motorneurons innervate the anterior abdominal wall and are active during expiration, defecation and vomiting.
    • (4) Cranial motorneurons innervate the muscles of the larynx and pharynx and are responsible for upper airway patency especially during inspiration.
  6. Higher Central Nervous System Mechanisms
    • Modulators of Respiratory Center Activity
    • (i) Descending reticular formation. Activity from the cortex and sub-cortex.
    • (ii) Suprapontine and from the limbic system and hypothalamus (activated by affective behavior: anger, rage, fear).
  7. Upper Airway Reflex Mechanisms
    • Modulators of Respiratory Center Activity
    • Sensory afferent fibers from the nasal passages, pharynx and larynx travel to the brain stem via the trigeminal nerve and glossopharyngeal nerves. They are responsible for protective reflexes such as the diving reflex, sneeze reflex, reflex swallowing and cough.
  8. Pulmonary Vagal Mechanoreceptors
    Pulmonary vagal mechanoreceptors exert their primary effects on breathing pattern rather than . Their afferent activity is conveyed via the vagus nerve in fibers that terminate in the NTS.
  9. Slowly adapting (stretch) receptors (SAR)
    • Pulmonary Vagal Mechanoreceptor
    • located in airway smooth muscle.
    • activated by lung inflation to promote inspiratory termination
    • (Hering-Breuer reflex).
  10. Rapidly adapting (irritant) receptors (RAR)
    • Pulmonary Vagal Mechanoreceptors
    • located in the airway epithelium.
    • stimulated by inhalation of irritant materials (noxious gases, dust) and by local mechanical distortion
  11. Juxtapulmonary capillary (J) receptors
    • Pulmonary Vagal Mechanoreceptors
    • non-myelinated free nerve endings in the alveolar-capillary interstitial space, which are stimulated by interstitial distortion, congestion, and pulmonary emboli to cause tachypnea
  12. Chest Wall and Peripheral Mechanoreceptors
    • Coordinate breathing during changes of posture and speech.
    • • Muscle spindles located on intrafusal muscle fibers of the intercostal muscles and, to a much lesser extent, the diaphragm. They respond to muscle stretching and, by stimulating respiratory motorneurons, stabilize ventilation and the chest wall.
    • • Golgi tendon organs found especially in the diaphragm. They respond to muscle tension, (i.e. contraction shortening) and inhibit respiratory motorneurons.
    • • Afferent projections from limb spindles, articular proprioceptors and free nerve endings sensitive to local pressure and pain can increase when stimulated. They might contribute to the hyperpnea of muscular exercise.
  13. Autonomic Regulation
    Adrenegic stimulation causes bronchodilatation by norepinephrine and epinephrine acting at Beta-adrenoceptors in airway smooth muscle. Cholinergic stimulation causes bronchoconstriction by acetylcholine acting at muscarinic receptors, also in airway smooth muscle.
  14. Central Chemosensitive Regions
    • These are deliberately termed "regions of chemosensitivity" rather than "chemoreceptors" as no morphologically discrete chemoreceptor cells have yet been demonstrated.
    • located bilaterally on the ventrolateral surface of the medulla and are exposed to CSF (which has very low buffering capacity).
    • The blood-brain barrier, which is relatively impermeable to H+ and HCO3- but which readily allows transfer of CO2.
    • The central chemosensitive regions are activated to increase by:
    • (i) increased local [H+];
    • (ii) increase in PaCO2, which causes PCSFCO2 and therefore [H+]CSF to rise.
  15. Peripheral Chemoreceptors
    • In man, these are the carotid bodies (the aortic bodies having little or no influence on Ve).
    • Located near the carotid bifurcation, they project to the medullary respiratory centers via the carotid sinus nerve and thence the glossopharyngeal nerve.
    • they are stimulated to increase by:
    • (i) reduced PaO2;
    • (ii) increased PaCO2;
    • (iii) increased arterial [H+].
    • Importantly, hypoxia potentiates the effects of PCO2 and H+, and vice versa.
  16. Ventilatory Response to Hypoxia
    • Inhalation of a hypoxic gas mixture normally leads to a hyperbolic increase in Ve if PaO2 is sufficiently low (i.e., ~ 60 mm Hg) (Figure 2 outward shift w higher PaCO2).
    • With higher PaCO2, the response is more marked; i.e., hypoxia is a more potent stimulus.
    • Conversely, when PaCO2 is lower the hypoxia is a less effective stimulus. The carotid bodies are the exclusive mediators of the ventilatory response to hypoxia.
  17. Ventilatory Response to Carbon Dioxide
    • Inhalation of a CO2-rich gas mixture stimulates Ve , to an extent that depends not only on the magnitude of the PaCO2 increase but also on the PaO2.
    • The Ve-PaCO2 relationship at a particular PaO2 is normally linear
    • (Figure 3: Ventilatory (Ve) response to arterial PCO2. );
    • the slope, delta(Ve)/delta(PaCO2) , is an index of the ventilatory responsiveness to CO2.
    • At a normal PaO2 of ~ 90-100 mm Hg, the slope is ~ 3 L/min/mm Hg.
    • This reflects contributions from both carotid body and central chemoreceptors, with the central component accounting for ~75%; i.e., the absence of the carotid bodies (which abolishes the Ve response to hypoxia in man) does not appreciably impair ventilatory responsiveness to CO2 (at normal PaO2).
    • Hypoxia steepens the slope of the Ve-PaCO2 relationship.
    • This reflects a potentiation of the CO2 stimulus by hypoxia through an action at the carotid bodies.
    • By contrast, hyperoxia provides a functional inactivation of the carotid bodies; as a result, the Ve-PaCO2 relationship is less steep and reflects solely the activity of the central chemoreceptors.
  18. Ventilatory Response to Hydrogen Ion
    • Acute increases in arterial [H+] induced by metabolic acidosis stimulate Ve through an effect mediated exclusively at the carotid bodies.
    • This response shifts the Ve-PaCO2 relationship to the left.
    • Thus, Ve is higher than normal at any given level of PaCO2 when there is concomitant metabolic acidosis (and lower when there is metabolic alkalosis).
Card Set
Control Cooper Lung