CONTROL OF VENTILATION- PART 1

CONTROL OF VENTILATION IN
HEALTH & DISEASE
Dr M A Nazrul
Control of ventiilation: Health & Disease- Dr M A Nazrul 1

INTRODUCTION
• Ventilation is the process of moving air in and out of the lungs.
• The ventilatory control mechanism must accomplish two tasks-
1. First it must establish the automatic rhythm for contraction of respiratory muscles.
2. Second it must adjust this rhythm to accommodate changing metabolic demands, varying
mechanical conditions and a range of episodic nonventilatory behaviours.
Reference- Medical Physiology 3E: Boron & Boulpaep –Chapter 32 Control of Ventilation

ANATOMY OF RESPIRATORY CONTROL CYCLE
CONTROLLER
EFFECTOR
LUNG VOLUME
SENSOR
Reference- Fishman’s Pulmonary Diseases and Disorders Fifth Edition –Chapter 11 Control of
Ventilation

In the 2nd century, Galen (a physician for gladiators in the
Greek city of Pergamon) performed the first experiments to
determine the location of the respiratory controller.
HISTORY

In 20th century, Lumsden used a similar approach in cats. He found that transection of the CNS between
the medulla and spinal cord (spinomedullary transection) causes ventilation to cease as a result of loss of
the descending input to phrenic and intercostal motor neurons in the spinal cord.
However, even after a spinomedullary transection, respiratory activity continues in muscles innervated by
motor neurons whose cell bodies reside in the brainstem.
It blocks ventilation by interrupting output to the diaphragm, not by eliminating the respiratory rhythm.

When Lumsden, in the 1940s, made a
transection between the pons and the
medulla (Fig. 32-2; pontomedullary
transection), he noticed that breathing
continued, but with an abnormal
gasping pattern.
Others have since observed relatively
normal breathing after a transection at
this level and concluded that the
gasping seen by Lumsden is due to
surgical damage to the rCPG in the
rostral medulla.
However, the consensus is that the
respiratory CPG is located in the
medulla but that other sites, including
the pons, shape the respiratory output
to produce the normal pattern

Lumsden found that a midpons transection has only a modest effect—an increase in tidal volume and a slight
decrease in respiratory rate.
A bilateral vagotomy, which carry sensory information from pulmonary stretch receptors—has a similar but
smaller effect.
However, combining a midpons transection with a bilateral vagotomy causes the animal to make prolonged
inspiratory efforts (apneusis) that are interrupted by only brief expirations.
A brainstem transection above the pons did not alter the basic respiratory pattern of eupnea.
These observations led Lumsden to propose that
(1) the caudal pons contains an apneustic center (i.e., it can cause apneusis)
(2) the rostral pons contains a pneumotaxic center that prevents apneusis.
The pneumotaxic center is located in the nucleus parabrachialis medialis(PB)and adjacent Kölliker-Fuse
nucleus(KF) in the rostral pons.

CONTROLLER
• The controller is a neuronal network within the central nervous system (CNS), which is responsible
for generating and modulating individual breaths and the overall breathing pattern, often referred to
as the respiratory central pattern generator(rCPG).
• Taken together, the Ventral respiratory column (VRC), Dorsal respiratory group (DRG) and Pontine
respiratory group (PRG) comprise the brainstem rCPG.
• Afferent signals from lung mechanoreceptors and peripheral chemoreceptors enter the
pontomedullary network via the nucleus of the solitary tract (nTS) in the DRG.
• The rhythmic output of the rCPG drives the activity of spinal phrenic, intercostal, and lumbar motor
neuron pools that innervate the muscles of respiration.
• rCPG is influenced by higher CNS structures, which allows for conscious control of the ventilatory
pattern
1. Lindsey BG, Rybak IA, Smith JC. Computational models and emergent properties of respiratory neural networks. Compr Physiol. 2012;2(3):1619–1670.
2. Molkov YI, Bacak BJ, Dick TE, Rybak IA. Control of breathing by interacting pontine and pulmonary feedback loops. Front Neural Circuits. 2013;7:16.

Overview of the respiratory central pattern
generator
The ventral respiratory column (VRC) is orientated in the rostral-
to-caudal direction.
The VRC extends from the retrotrapezoid nucleus (RTN) adjacent
to the rostral facial nucleus (VII) superiorly, to the caudal ventral
respiratory group (cVRG) near the spinomedullary junction
inferiorly.
The main areas of rhythmically active VRC respiratory neurons
are in the Bötzinger complex (BötC), pre-Bötzinger complex (pre-
BötC), rostral ventral respiratory group (rVRG), and cVRG.
The parafacial respiratory group (pFRG) overlaps anatomically
with the RTN, and together these regions include intrinsically
bursting neurons which may contribute to rhythm generation.
Peripheral chemo- and mechanosensory inputs are transmitted to
the nucleus of the solitary tract (nTS) in the dorsal respiratory
group (DRG).
The pontine respiratory group (PRG) includes the Kölliker–Fuse
(K–F) and the parabrachial (PB) nuclei which contain respiratory-
modulated neurons.
Ventilation

PHASES OF RESPIRATION
The neural respiratory cycle comprises three phases-
• Inspiration involves ramp-like increases in inspiratory motor neuron firing, which drive phrenic nerve
activity throughout this phase. [Early Inspiratory neuron]
• The first phase of expiration is often called post-inspiration, because inspiratory motor neurons
are still active. Persistent inspiratory motor activity during this phase acts to slow the exit of air from
the lungs. [Late-onset inspiratory neuron]
• During the second phase of expiration , expiratory muscles are typically electrically silent. During
this phase of passive relaxation, gas is expelled as the lungs and chest wall return to their
equilibrium state.
Reference-Control of Ventilation in Health and Disease Susmita Chowdhuri, MD and M. Safwan Badr,
MD

Richter DW. Generation and maintenance of the respiratory rhythm. J Exp Biol. 1982;100:93–107

EFFECTOR

SENSOR
• CHEMORECEPTORS
Peripheral chemoreceptors
1.Carotid bodies
2.Aortic bodies
Central chemoreceptors
• MECHANORECEPTORS
Slowly adapting Pulmonary stretch receptors
Rapidly adapting Pulmonary stretch(irritant) receptors
Bronchial J receptors
C-Fiber receptors
Muscle spindle
Muscle tendon organ
Ventilation

PERIPHERAL
CHEMORECEPTORS
• The body has two sets of peripheral chemoreceptors: the carotid bodies, one located at the bifurcation of
each of the common carotid arteries; and the aortic bodies, scattered along the underside of the arch of the
aorta.
• The chemo sensitive cells of the carotid body are the type I or glomus cells.
• A decrease in arterial PO2 is the primary stimulus for the peripheral chemoreceptors. Increases in PCO2 and
decreases in pH also stimulate these receptors and make them more responsive to hypoxia.

Control of ventiilation: Health & Disease- Dr M A Nazrul
17
Hypoxia, hypercapnia, and acidosis inhibit K+channels, raise glomus cell [Ca2+] and release
neurotransmitters

CENTRAL CHEMORECEPTORS
• When the blood-gas parameters are nearly normal, the central chemoreceptors are the primary source of feedback for
assessing the effectiveness of ventilation
• The central chemoreceptors are responsible for approximately two-thirds of the ventilatory response to carbon
dioxide/pH
• They are located within the brain parenchyma and are bathed in brain extracellular fluid ,which is separated from
arterial blood by the blood-brain barrier (BBB). The BBB has a high permeability to small, neutral molecules such as
O2 and CO2 but a low permeability to ions such as Na+, Cl−, H+, and HCO3-

MECHANORECEPTORS
• Slow adapting receptors-Lung stretch receptors are present in the airway smooth muscle of the distal airways.
These slowly adapting receptors are stimulated by lung inflation
• Rapidly adapting receptors respond to changes in airway mechanical properties that accompany lung inflation and
deflation, and become more active as the rate of airflow increases. These lung mechanoreceptors are primarily
located in the epithelial and submucosal layers of the larger airways, accounting for their sensitivity to inhaled agents.
• Bronchial J receptors are named for their juxtacapillary location. These lung mechanoreceptors project centrally
through unmyelinated fibers, and respond to pulmonary vascular congestion associated with increases in pulmonary
artery and capillary pressure. Stimulation contributes to the increase in respiratory frequency and a decrease in tidal
volume in response to pulmonary edema.
Ventilation

• Bronchial C receptors are named for their sensitivity to capsaicin, and are located in the airway wall. Activation of C
fibers with capsaicin or bradykinin produces cough and a rapid, shallow breathing pattern. Unlike other lung receptors
described here, bronchial C receptors are relatively insensitive to mechanical stimulation and changes in lung volume.
• Muscle spindles transduce muscle length. These mechanoreceptors are plentiful in the intercostal muscles. Muscle
spindles tend to augment breathing when activated.
• Muscle tendon organs are located in series with muscle fibers in the tendon and are activated as muscle fibers generate
force. Thus, these mechanoreceptors sense the efficiency of force generation and inhibit breathing when activated.
• The rib cage joints and upper airways (larynx, pharynx, and nasal cavity) also contain receptors that impact control of
ventilation. For example, cold air stimulation of the pharynx initiates the cough reflex.
Ventilation

CONTROLLER
EFFECTOR
LUNG VOLUME
SENSOR
rCPG
Inspiration/Expiration
Muscles of
respiration
Chemoreceptors
Mechanoreceptors
Ventilation

In the upcoming seminar:
• Factors AffectingControlofventilation-Age,Sex,Loop gain, Exercise,Altitude, Geneticfactors,Sleep,
etc.
• Associated Diseases

CONTROL OF VENTILATION- PART 1

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