CONTROL OF

BREATHING

Dr.Anto Mathew
• Respiration is a reflex process.

• It can be controlled voluntarily for a short period of about 40 seconds.

• By practice, breathing can be withheld for a long period.

• Normally, quiet regular breathing occurs because of two regulatory
mechanisms:
1. Nervous or neural mechanism

2. Chemical mechanism.
 NERVOUS MECHANISM
• Nervous mechanism that regulates the respiration includes:
• 1. Respiratory centers
• 2. Afferent nerves
• 3. Efferent nerves.
RESPIRATORY CENTERS
• Respiratory centers are group of neurons, which control the rate, rhythm and
force of respiration.
• These centers are bilaterally situated in reticular formation of the brainstem .
• Classified into two groups:
A. Medullary centers
1. Dorsal respiratory group of neurons
2. Ventral respiratory group of neurons
B. Pontine centers
3. Apneustic center
4. Pneumotaxic center
MEDULLARY CENTERS
• 1. Dorsal Respiratory Group of Neurons
Dorsal respiratory group of neurons are diffusely situated in the nucleus
of tractus solitarius which is present in the upper part of the medulla
oblongata .These neurons are collectively called inspiratory center.
• All the neurons of dorsal respiratory group are inspiratory neurons
and generate inspiratory ramp by the virtue of their auto rhythmic
property.
• Dorsal group of neurons are responsible for basic rhythm of
respiration
Ventral Respiratory Group of Neurons

• Ventral respiratory group of neurons are present in nucleus ambiguous and nucleus
retroambiguous.
• These two nuclei are situated in the medulla oblongata, anterior and lateral to the
nucleus of tractus solitarius.
• Earlier, the ventral group neurons were collectively called expiratory center.But Ventral
respiratory group has both inspiratory and expiratory neurons.
• Inspiratory neurons are found in the central area .
• Expiratory neurons are in the caudal and rostral areas of the group.
• Normally, ventral group neurons are inactive during quiet breathing and become active
during forced breathing.
• During forced breathing, these neurons stimulate both inspiratory muscles and
expiratory muscles.
PONTINE CENTERS
• Apneustic Center.
• Apneustic center is situated in the reticular formation of lower pons.
• Apneustic center increases depth of inspiration by acting directly on
dorsal group neurons
Pneumotaxic Center
• Pneumotaxic center is situated in the dorsolateral part of reticular formation in
upper pons. It is formed by neurons of medial parabrachial and subparabrachial
nuclei.
• Primary function of pneumotaxic center is to control the medullary respiratory
centers, particularly the dorsal group neurons.
• It acts through apneustic center.
• Pneumotaxic center inhibits the apneustic center so that the dorsal group
neurons are inhibited. Because of this, inspiration stops and expiration starts.
• Pneumotaxic center influences the switching between inspiration and expiration.
• Pneumotaxic center increases respiratory rate by reducing the duration of
inspiration
CONNECTIONS OF RESPIRATORY
CENTERS
• Efferent Pathway
• Nerve fibers from respiratory centers leave the brainstem and descend in
anterior part of lateral columns of spinal cord.
• These nerve fibers terminate on motor neurons in the anterior horn cells of
cervical and thoracicsegments of spinal cord.
• From motor neurons of spinal cord, two sets of nerve fibers arise:
1. Phrenic nerve fibers (C3 to C5), which supply the diaphragm
2. Intercostal nerve fibers (T1 to T11), which supply the external intercostal
muscles.
• Vagus nerve also contains some efferent fibers from the respiratory centers.
Afferent Pathway
• Respiratory centers receive afferent impulses from:
1.Peripheral chemoreceptors and baroreceptors via branches of
glossopharyngeal and vagus nerves
2. Stretch receptors of lungs via vagus nerve.
• By receiving afferent impulses from these receptors, respiratory
centers modulate the movements of thoracic cage and lungs through
efferent nerve fibers
• Role of Pontine Centers
• Pontine respiratory centers regulate the medullary centers.
• Apneustic center accelerates the activity of dorsal group of neurons and
the stimulation of this center causes prolonged inspiration.
• Pneumotaxic center inhibits the apneustic center and restricts the
duration of inspiration.
• Neuronal populations in the Botzinger complex (BotC) are the major
source of expiratory network activity during normal breathing.
• BotC neurons are important for control of the transition between
inspiratory and expiratory activities and maintenance of the rhythmicity
of normal breathing
CHEMICAL MECHANISM
• Chemical mechanism of regulation of respiration is operated through
the chemoreceptors.
• Chemoreceptors are the sensory nerve endings, which give response
to changes in chemical constituents of blood.
• Types of Chemoreceptors.

1. Central chemoreceptors

2. Peripheral chemoreceptors
CENTRAL CHEMORECEPTORS
• Central chemoreceptors present in the brain.
• Central chemoreceptors are situated in postero lateral wall of medulla
oblongata, close to the dorsal respiratory group of neurons.
• Chemo receptors are in close contact with blood and cerebrospinal
fluid.
• They sense high PCo2 and low PH ,not PO2
• Central chemoreceptors are connected with respiratory centers, particularly
the dorsal respiratory group of neurons through synapses.

• Main stimulant for central chemoreceptors is the increased hydrogen ion

concentration.

• However, if hydrogen ion concentration increases in the blood, it cannot

stimulate the central chemoreceptors because, the hydrogen ions from blood
cannot cross the bloodbrain barrier and blood-cerebrospinal fluid barrier.

• On the other hand, if carbon dioxide increases in the blood, it can easily cross
the blood-brain barrier and blood cerebrospinal fluid barrier
• Change in H+ concentration of blood is poorly reflected in CSF, as H+
penetrates very slowly into the brain.

• However, molecular carbon dioxide diffuses readily into CSF.

• CO2 that enters the CSF is immediately hydrated to form H2CO3. H2CO3
dissociates to form H+ and HCO3−.

• blood PCO2 influences the pH of CSF.

• In fact, concentration of H+ in interstitial fluid in the brain parallels the
PCO2 level in arterial blood.

• The concentration of H+ in CSF stimulates central chemoreceptors that

increase respiration and the magnitude of stimulation is proportional to its
concentration.
PERIPHERAL CHEMORECEPTORS
• Peripheral chemoreceptors are located in the carotid and aortic
bodies.
• They respond to changes in PO2, PCO2 and pH in arterial blood.
• However, they are more sensitive to decreased arterial PO2 (hypoxia)
though they also sense increase in PCO2 and decreased pH.
• Carotid and aortic bodies send signals to the dorsal respiratory group
(DRG)of neurons in medulla to increase ventilation.
 Carotid Bodies
• They are located at the bifurcations of the common carotid arteries near the base
of the skull on both sides
• Afferent nerves from the carotid bodies travel to the brainstem in the
glossopharyngeal nerves.
• Two special features of carotid bodies are:
1. They receive unusually high blood flow, which is highest in the body per unit-
weight of the tissue.
The blood flow is about 2 L per 100 g of tissue/min, which is approximately 40
times the blood flow to the brain.
2. They have a high metabolic rate, which is about three times greater than that of
brain.
• Due to the greater blood flow, the carotid bodies easily detect minor changes in
PO2, PCO2 and pH of blood
• Carotid body consists of two types of cells: Type I and Type II.

• The type I are called glomus cells voltage gaited channel.

• The type II cells are called sustentacular cells

Aortic Bodies

• Aortic bodies are located along the ascending aorta and arch of the aorta.
They are innervated by vagal afferents.

• They also contain glomus cells similar to that of carotid body.

• However, the responses of aortic chemoreceptors to stimuli are somewhat

different from the carotid chemoreceptors.

• Aortic chemoreceptors are relatively less effective than carotid

chemoreceptors in the regulation of respiration
 Sensitivity of Chemoreceptors
• Hypoxia is the major stimulus for activation of peripheral chemoreceptors.
• The response is most effective at PO2 less than 60 mm Hg
1.In hypoxia, hemoglobin (Hb) is less saturated with O2. Oxy-Hb is a stronger
acid than Hb. Thus, with fall in arterial PO2, the H+ of arterial blood falls due
to less saturation of Hb with O2. The fall in H+ inhibits respiration.
2. Increased ventilation due to hypoxia decreases PCO2 that in turn inhibits
ventilation. Therefore, unless hypoxia is strong enough to overcome the
inhibitory effect of decreased H+ and PCO2 in arterial blood on ventilation, its
effect on ventilation is not prominent. When PO2 is less than 60 mm Hg,
hypoxic drive becomes strong enough to override these inhibitory effects
 Hypercapnia

• The rate of discharge of carotid and aortic chemoreceptors increases linearly with
increase in PaCO2.

• This directly increases the ventilatory response to carbon dioxide.

• CO2 is produced by metabolisms.

• Thus, increased metabolism stimulates respiration, which in turn removes CO2 from
the body.

• In fact, ventilation remains elevated till arterial PCO2 returns to normal.

1.Increase in PaCO2 stimulates peripheral chemoreceptors by increasing CO2 in
glomus cells. In fact, H+ formed form H2CO3 in the glomus cells is the actual
stimulus rather than the molecular CO2.
Effect of PaCO2 on ventilation is mediated up to 40% by peripheral
chemoreceptors.

2. It should be noted here that hypoxia affects ventilation mainly via peripheral
chemoreceptors, whereas hypercapnia affects ventilation mainly via central
chemoreceptors.

3. The effect of CO2 on ventilation is studied by inhaling gas mixture containing

CO2. Increase in alveolar PCO2 increases arterial PCO2 that stimulates
ventilation. Hyperventilation removes CO2 from blood and decreases alveolar
PCO2.
4. However, alveolar PCO2 does not become normal and remains elevated.
Therefore, stimulation of ventilation continues till the individual continues to
inhale CO2 gas mixture. Increase in alveolar PCO2 has almost a linear
relationship with increase in ventilation

5. When, CO2 content of atmospheric air is high (CO2 content of inspired air
is more than 7%), PCO2 of alveolar air and arterial blood increase abruptly.
Elimination of CO2 from body becomes ineffective in this condition and CO2
accumulates in blood.

6.High hypercapnia causes CNS depression. Initially, there will be headache

and confusion, which fast leads to coma. The condition is called CO2
narcosis.
 FACTORS AFFECTING
RESPIRATORY CENTERS
• Impulses from Stretch Receptors of Lungs: Hering-Breuer Reflex
• HeringBreuer reflex is a protective reflex that restricts inspiration and prevents
overstretching of lung tissues.
• It is initiated by the stimulation of stretch receptors of air passage.
• These receptors are situated on the wall of the bronchi and bronchioles.
• Expansion of lungs during inspiration stimulates the stretch receptors. Impulses
from stretch receptors reach the dorsal group neurons via vagal afferent fibers
and inhibit them.
• So, inspiration stops and expiration starts Thus, the overstretching of lung
tissues is prevented.
• However, HeringBreuer reflex does not operate during quiet breathing. It
operates, only when the tidal volume increases beyond 1,000 mL.
 Impulses from ‘J’ Receptors of Lungs
• ‘J’ receptors are juxtacapillary receptors which are present on the wall of the alveoli
and have close contact with the pulmonary capillaries. Sense fluid in the interstitium.
• Nerve fibers from these receptors are nonmyelinated and belong to C type.
• Few receptors are found on the wall of the bronchi.
• Conditions when ‘J’ receptors are stimulated
i. Pulmonary congestion
ii. Pulmonary edema
iii. Pneumonia
iv. Over inflation of lungs
v. Microembolism in pulmonary capillaries
vi. Stimulation by exogenous and endogenous chemical substances such as
histamine,bradykinin, serotonin and
• J receptor reflex TRIAD: hyperventilation,bradycardia,hypotension.

Impulses from Irritant Receptors of Lungs

• Irritant receptors are stimulated by irritant chemical agents such as
ammonia and sulfur dioxide.
• These receptors send afferent impulses to respiratory centers via vagal
nerve fibers. Stimulation of irritant receptors produces reflex
hyperventilation along with bronchospasm.
• Hyperventilation along with bronchospasm prevents further entry of
harmful agents into the alveoli
Impulses from Thermoreceptors
• Thermoreceptors are cutaneous receptors, which give response to change in
the environmental temperature.
• Thermoreceptors are of two types, namely receptors for cold and receptors for
warmth.
• When body is exposed to cold or when cold water is applied over the body,
cold receptors are stimulated and send impulses to cerebral cortex via somatic
afferent nerves.
• Cerebral cortex in turn, stimulates the respiratory centers and causes
hyperventilation.
Impulses from Proprioceptors
• Proprioceptors are the receptors which give response to change in the
position of body.
• These receptors are situated in joints, tendons and muscles.
Proprioceptors are stimulated during the muscular exercise and send
impulses to brain, particularly cerebral cortex, through somatic afferent
nerves.
• Cerebral cortex in turn causes hyperventilation by sending impulses to
medullary respiratory centers.
Ventilatory Acclimatization to
Oxygen Disturbances

• Acute exposure to altitude results in hypoxemia, which produces an immediate

increase in minute ventilation mediated through the peripheral chemoreceptors
and characterized by an increase in frequency (respiratory rate) and amplitude
(tidal volume).
• With ongoing exposure, ventilation continues to increase for several days resulting
in a sustained gradual decrease in arterial PO2.
• Chronic exposure to high altitude, lasting from several hours to months, results in
acclimatization.
• This adaptation to high altitude is characterized by a gradual rise in minute
ventilation with a time course depending on the altitude.
• In humans, at very high altitudes (∼8000 m), this process may take at least 30
days.people living in high altitude for long periods of time the PCO2 falls to the
lower level of normal or even less.
• A number of physiological mechanisms of ventilatory acclimatization to hypoxia
have been identified.

• They include
(a) plasticity in O2 sensitivity of the carotid body chemoreceptors,
(b) the CNS integration of peripheral O2-sensitive reflexes (e.g., carotid body
chemoreflex),
(c) plasticity of CNS mechanisms of acute O2 sensing,
(d) the CNS integration of other non chemoreflex ventilatory control pathways
such as reflexes from pulmonary vagal chemoreceptors or respiratory rhythm
generators.
For example, hypoxia-inducible factor-1 (HIF-1) is a key regulator of O2-sensitive
gene expression in the brain, and increases in HIF-1 have been identified in
respiratory nuclei of the CNS as soon as 1 hour after hypoxemia .

Hence, O2 sensing by HIF-1α could be involved in the ventilatory acclimatization

to high altitude by increasing the expression of genes with products known to
modulate the hypoxic ventilatory response
Oxygen-Induced Hypercapnia in Chronic
Obstructive Pulmonary Disease
• In severe chronic obstructive pulmonary disease (COPD), transient falls in
ventilation and respiratory acidosis have been reported with breathing 100%
oxygen for 20 minutes.

• Initially CO2 retention with oxygen treatment was thought to result from the
suppression of the hypoxic drive mediated by carotid chemoreceptors.

• Subsequently, additional mechanisms have been shown to contribute to oxygen-

induced hypercapnia in COPD as follows:
(1) The increase in oxygen tension in lung units with low ventilation/perfusion
(V/Q) ratios can blunt hypoxic pulmonary vasoconstriction in these low V/Q lung
units, thus diverting perfusion away from high V/Q lung units yielding higher dead
space;

(2) the Haldane effect, which refers to the reduction in hemoglobin affinity for
CO2 with the binding of oxygen to hemoglobin.
With increased blood oxygen levels, the Haldane effect promotes dissociation of
carbon dioxide from hemoglobin and leads to a small increase in PaCO2;

(3) suppression of hypoxic drive.

(4) increases in FiO2 which occur with noninvasively delivered oxygen as minute
ventilation falls.
Disturbances of Respiratory Rhythm
• Congenital central hypoventilation syndrome (CCHS), occasionally
referred to as Ondine’s curse, is a rare neurological disorder
characterized by inadequate breathing during sleep and, in more
severely affected individuals, also during waking periods.
• Patients congenitally lack or have poor chemosensitivity to both
hypercapnia and hypoxia, and suffer from inadequate ventilation.

• patients with CCHS have an increased polyalanine repeat expansion

mutation (PARM) in the paired-like homobox 2B (PHOX2B) gene.
• There is a correlation with the number of polyalanine repeat expansion
genotype and the need for continuous ventilatory support.

• The disease typically presents in childhood, but rare adult-onset cases have
been reported.

• A number of conditions are associated with CCHS and reflect the autonomic
nervous system dysregulation, including Hirschsprung disease (about 20% of
cases) and tumors of neural crest origin (neuroblastomas).
Rett syndrome

• Ia a neurodevelopmental disorder that occurs almost exclusively in

females.
• After a period of initially normal development, affected patients
experience loss of speech and purposeful hand use, stereotypic hand
movements, gait abnormalities, and breathing abnormalities
• Most cases result from mutations in the gene encoding methyl-CpG-
binding protein 2 (Mecp2). Loss of Mecp2 function is associated with
an irregular breathing pattern.
THANK YOU