The ventilatory control mechanism must accomplish two tasks: establishing the automatic rhythm of respiration and adjusting the rhythm based on metabolic demands, mechanical conditions, and other behaviors. This is accomplished by networks of respiratory neurons located in the dorsal and ventral respiratory groups in the medulla that generate the respiratory rhythm through intrinsic properties and synaptic interactions. These neurons are modulated by peripheral and central chemoreceptors that sense changes in blood gases like oxygen and carbon dioxide levels to adjust ventilation. Higher brain centers and afferent feedback further influence the respiratory control system.
2. The ventilatory control mechanism must accomplish two tasks.
First, it must establish the automatic rhythm for contraction of the respiratory muscles.
Second, it must adjust this rhythm to accommodate changing metabolic demands (as reflected
by changes in blood PO2 , PCO2 , and pH), varying mechanical conditions (e.g., changing
posture), and a range of episodic, nonventilatory behaviors (e.g., speaking, sniffing, eating).
3. 1. Respiratory neurons
2. How these neurons generate the automatic rhythm of ventilation?
3. The control of ventilation by arterial blood gases.
4. How afferent feedback and higher CNS centers modulate ventilation?
6. CONT…
1. The dorsal respiratory group (DRG) primarily contains inspiratory neurons.
2. It extends for about one third of the length of the medulla and is located bilaterally in and
around the nucleus tractus solitarii (NTS), which receives sensory input from all viscera of the
thorax and abdomen and plays an important role in control of the autonomic nervous
system.
3. The NTS is viscerotopically organized, with the respiratory portion of the NTS ventrolateral to
the tractus solitarius, just beneath the floor of the caudal end of the fourth ventricle. These
NTS neurons, as well as some immediately adjacent neurons in the dorsal medulla, make up
the DRG.
8. CONT…
1. The rostral VRG (or Bötzinger complex, BötC)
2. The intermediate VRG, pre-Bötzinger complex (preBötC)
3. The caudal VRG
9. GENERATION OF THE RESPIRATORY RHYTHM
1. Eupneic breathing is highly stereotyped and consists of two phases—inspiration and
expiration.
10. 1. Underlying the activity of the phrenic nerve—and the other motor nerves supplying the
muscles of inspiration and expiration—is a spectrum of firing patterns of different RRNs
located within the DRG and VRG.
2. RRNs can be broadly classified as inspiratory or expiratory, but each class includes many
subtypes, based on how their firing patterns correlate with the respiratory cycle. Each
subtype presumably plays a unique role in generating and shaping respiratory output— that
is, the activity of the nerves to each respiratory muscle.
11. THE FIRING PATTERNS OF RRNS DEPEND ON
THE ION CHANNELS AND THE SYNAPTIC
INPUTS
1. Intrinsic Membrane Properties
2. Synaptic Input
In addition to synaptic
input from RRNs that
occurs rhythmically, in
phase with breathing,
respiratory neurons
also receive input
from other neuronal
systems
12. 1. Pacemaker properties and synaptic interactions may both contribute to the generation of the
respiratory rhythm
2. Peter Getting
3. Network models
13. THE RESPIRATORY CPG FOR EUPNEA COULD RESIDE IN A
SINGLE SITE OR IN MULTIPLE SITES OR COULD EMERGE FROM
A COMPLEX NETWORK
Flourens
Santiago Ramón y Cajal
1. Restricted-Site Model
2. Distributed Oscillator Models
3. Emergent Property Model
14. CHEMICAL CONTROL OF VENTILATION
PERIPHERAL CHEMORECEPTORS
1. Sensitivity to Decreased Arterial PO2
17. THE GLOMUS CELL IS THE CHEMOSENSOR IN THE
CAROTID AND AORTIC BODIES
18.
19. Hypoxia Hypercapnia Acidosis
Heme containing
protein
↑[cAMP]i
↑GSH/GSSG
↑i CO2 → ↑i H+ Inhibits acid-base
transporters → ↑i H+
Inhibition of BK K+
Activaiton of voltage
gated Ca2+
Release of
neurotransmitters
Transmitter binding and
firing of afferent nerves
20. CENTRAL CHEMORECEPTORS
1. Isidore Leusen
2. Hans Loeschcke, Marianne Schläfke, and Robert Mitchell
3. More recent work indicates that the VLM is not the only location of central chemoreceptors.
For example, studies on brain slices and cultured cells show that acidosis stimulates neurons
in many brainstem nuclei. Besides the VLM, these include the medullary, the nucleus
ambiguus, and the NTS, all in the medulla, as well as the locus coeruleus and hypothalamus.
21.
22. SOME NEURONS OF THE MEDULLARY RAPHE
AND VENTROLATERAL MEDULLA ARE
UNUSUALLY PH SENSITIVE
1. Serotonin
2. GABA
25. RESPIRATORY ACIDOSIS ACCENTUATES
THE ACUTE RESPONSE TO HYPOXIA
Chronic hypercapnia in pulmonary disease
Emphysema,or with muscle weakness (e.g.,
amyotrophic lateral sclerosis, neuropathies,
and myopathies)
Central drive decreases due to correction oh
CSFpH and BECFpH.
Then the main drive is from periphereal
receptors.
Increased supplmenetal therapy can cause Co2
narcosis.
26. MODULATION OF VENTILATORY
CONTROL
1. Stretch and chemical/irritant receptors in the airways and lung parenchyma provide
feedback about lung volume and the presence of irritants
2. Slowly Adapting Pulmonary Stretch Receptors (PSRs) eg; Hering-Breuer reflex
3. Rapidly Adapting Pulmonary Stretch (Irritant) Receptors activated by PG, serotonin,
bradykinin, NH4+, cigarette smoke.
4. C-Fiber Receptors (juxtacapillary or J receptors), they elicit a triad of rapid and shallow
breathing, bronchoconstriction, and increased secretion of mucus into airway.
27. 1. Higher brain centers coordinate ventilation with other behaviors and can override the
brainstem’s control of breathing eg; speaking, sniffing, and regulating temperature (e.g.,
panting in dogs)
2. Coordination with Voluntary Behaviors That Use Respiratory Muscles eg: voluntarily
hyperventilating, breath-holding, speaking, singing, whistling, and playing musical wind
instruments
3. Coordination with Complex Nonventilatory Behaviors eg:yawning, chewing, swallowing,
sucking, defecating, grunting, and vomiting.
4. Modification by Affective States.
5. Balancing Conflicting Demands of Gas Exchange and Other Behaviors
28. 1. The respiratory apparatus engages in a variety of motor behaviors that help maintain normal
lung function and gas exchange by protecting the alveoli from collapse or preventing
obstruction of the upper airways.
2. Sighs
3. Yawns
4. Coughs
5. Sneezes
