May 8, 2023 Control of Respiration 1
Control of Respiration
Neural MechanismsChemical Mechanisms
May 8, 2023 Control of Respiration 2
Introduction
Function of respiration include– Regulation of alveolar ventilation
•Maintain constant supply of O2 to tissues– Normal 250 ml O2 /min– This can increase to 20 times during
exercise•To eliminate CO2 from the tissues•Thus PO2, PCO2, pH
– Maintained at constant values or nearly constant values
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Introduction
Other functions of respiration include– Phonation, singing, laughing,
whistling etcIn all these
– Extremely complicated respiratory movements are performed
– Require coordinated control
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Neural Control of Respiration
Two neural control mechanisms regulate respiration– One responsible
for voluntary control
– The other one for automatic control
Cerebral cortex
Pons & medulla
Spinal cord
Respiratory muscles
Corticospinal tract
Reticulospinal tract
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Neural Control of Respiration
Voluntary control system – Located in
cerebral cortex– Send impulses to
respiratory muscles via• Corticospinal
tracts (CST)
Cerebral cortex
Pons & medulla
Spinal cord
Respiratory muscles
Corticospinal tract
Reticulospinal tract
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Control Systems for Respiration
Automatic system– Located in pons
and medulla oblongata
– Efferent output from this system to respiratory muscles • Located in spinal
cord close to CST
Cerebral cortex
Pons & medulla
Spinal cord
Respiratory muscles
Corticospinal tract
Reticulospinal tract
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Control Systems for Respiration
Nerves serving inspiration converge in ventral horns– C3,4,5 (phrenic
nerve)– External intercostal
motor neurons Fibres concerned
with expiration– Converge on internal
intercostals motor neurons
Cerebral cortex
Pons & medulla
Spinal cord
Respiratory muscles
Corticospinal tract
Reticulospinal tract
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Control Systems for Respiration
Reciprocal activity– Motor neurons to
expiratory muscles• Inhibited when
those to inspiratory muscles are activated &vice versa
Cerebral cortex
Pons & medulla
Spinal cord
Respiratory muscles
Corticospinal tract
Reticulospinal tract
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Breathing Pattern
During quite breathing
Inspiration is brought about by– Progressive
increase in activation of inspiratory muscles
End of inspiration associated with– Rapid decrease in
excitation
Inspira
tion
Expir
ation
2 sec 3 sec
Electrical activity (diaphragm)
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Breathing Pattern
The progressive activation of inspiratory muscle cause– Lungs to fill at
constant rate until tidal vol reached
End of inspiration associated – Rapid decrease in
excitation of inspiratory muscles• Expiration occurs
Inspira
tion
Expir
ation
2 sec 3 sec
Electrical activity (diaphragm)
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Respiratory Neurons
Two types of brainstem respiratory neurons
Inspiratory neurons (I-neurons)– Discharge during inspiration
Expiratory neurons(E-neurons)– Discharge during expiration
• During quite breathing – Remain silent
• Become active only when ventilation is increased
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Respiratory Centers
IX
X
XI
XII
D R G
V R G
Vag
us,
glos
opha
ryng
eal
Pneumotaxic center
DRG
VRG
Apneustic center
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Respiratory Centers
Composed of several groups of neurons– Located
bilaterally in •Medulla
oblongata•Pons
IX
X
XI
XII
D R G
V R G
Pneumotaxic center
Apneustic center
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Respiratory Centers
Three major collection of neurons– Dorsal respiratory
group (DRG)– Ventral respiratory
group (DRG)– Pneumotaxic center– ? Apneustic center
IX
X
XI
XII
D R G
V R G
Apneustic center
Pneumotaxic center
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Respiratory Centers
Dorsal respiratory group (DRG)– Located on the
dorsal portion of medulla• In or near the
Nucleus of Tractus Solitarius(NTS)
IX
X
XI
XII
D R G
V R G
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Respiratory Centers
NTS– Sensory terminal
of vagus & glossopharyngeal• Transmit sensory
signals from– Peripheral
chemoreceptors– Baroreceptors– Receptors in the
lungs
IX
X
XI
XII
D R G
V R G
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Respiratory Centers
DRG made up– Of I – neurons
• Some project monosynaptically to phrenic nerve motor neurons (MN)
– Cause inspiration
IX
X
XI
XII
D R G
V R G
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Respiratory Centers
VRGLong column
extends through – Nucleus ambiguus– Nucleus
retroambiguus in the ventral medulla
IX
X
XI
XII
D R G
V R G
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Respiratory Centers
VRG has both I & E neurons– E – neurons at its
rostral end– I-neurons at the mid
portion– E-neurons at its
caudal end• Some of these
neurons project to– Respiratory
motor neurons
IX
X
XI
XII
D R G
V R G
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Generation of Breathing Pattern
Rhythmic respiratory pattern– Appear to be
initiated by the • Rhythmic
discharges of neurons in the medulla and pons
IX
X
XI
XII
D R G
V R G
A
D
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Generation of Breathing Pattern
Trans-section of brain– Below medulla
• Stops respiration– Above the pons
• Automatic breathing is still present
Neurons in medulla & pons– Responsible for
generating the rhythmic respiratory movements
IX
X
XI
XII
D R G
V R G
A
D
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Generation of Breathing Pattern
The actual mechanism responsible for – Rhythmic respiratory
discharge not known However,
– Group of pacemaker neurons have been identified• Pre-Böttzinger
Complex• Area between nucleus
ambiguus & lateral reticular nucleus
IX
X
XI
XII
D R G
V R G
A
D
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Pontine & vagal Influence
The spontaneous rhythmic discharges of medullary neurons is modified by– Neurons in the
pons– Afferents in the
vagus from receptors in the airways and lungs
IX
X
XI
XII
D R G
V R G
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Pontine & vagal Influence
Pneumotaxic center located in– Nucleus
parabrachialis in dorsal lateral pons
Contain both– I-neurons & E-neurons– Also contain neurons
that are active in both phases of respiration
IX
X
XI
XII
D R G
V R G
Pneumotaxic center
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Pontine & vagal Influence
When this area is damaged – Respiration becomes
slower– Tidal volume greater
Pneumotaxic center may play a role– Switching
between inspiration & expiration
IX
X
XI
XII
D R G
V R G
Pneumotaxic center
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Pontine & vagal Influence
Apneustic center– Situated in lower
pons Send signals to DRG
– Prevent “switching-off” of respiratory ramp (increase duration of inspiration)
– Lungs become completely filled with air
IX
X
XI
XII
D R G
V R G
Pneumotaxic center
Apneustic center
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Pontine & vagal Influence
Apneustic center is inhibited by – Vagus & pneumotaxic
center Vagotomy &
destruction of pneumotaxic center causes– Prolonged period of
inspiration• Apneusis
IX
X
XI
XII
D R G
V R G
Pneumotaxic center
Apneustic center
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Chemical Control
Pulmonary ventilation– Regulated to meet different levels of
metabolic demands• Supply O2 • Elimination of CO2
Achieved by feed back control of respiratory center activity– In response to chemical
composition of blood•PCO2, H+, PO2
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Chemical Control
Types of receptors– Central chemo-receptors– Peripheral receptors– Others
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Central Chemoreceptors
Chemosensitive neurons– Bilateral beneath
the ventral medulla
Sensitive to changes in PCO2 & H+
H+ only important direct stimulus
DRG
CO2 + H2O ⇌ H2CO3 ⇌ HCO3- +
H+
Chemosensitive neurons
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Central Chemoreceptors
H+ crosses the blood-brain –barrier (BBB) very poorly– Changes in H+ in
blood have less immediate effect on respiration
CO2 diffuse easily across BBB– It is then hydrated
and dissociates to H+
& HCO3-
DRG
CO2 + H2O ⇌ H2CO3 ⇌ HCO3- +
H+
Chemosensitive neurons
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Central Chemoreceptors
An increase CSF CO2 causes chemoreceptors to stimulate respiration
A decrease CSF CO2 causes chemoreceptors to inhibit respiration
DRG
CO2 + H2O ⇌ H2CO3 ⇌ HCO3- +
H+
Chemosensitive neurons
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Peripheral Chemoreceptors Located in the carotid & aortic
bodiesThese receptors respond to
– Lowered arterial O2 tension– Rise in arterial CO2 tension– Increase in H+ conc in arterial
blood
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Peripheral ChemoreceptorsArterial O2 tension
– Only site in the body that detect changes in O2 tension of body fluids
Peripheral chemoreceptors– Receive a lot of blood flow for
their size•2000 ml/100 gm/min (cf brain = 54
ml/100 gm/min)
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Peripheral ChemoreceptorsThus they monitor–O2 tension rather than O2
content O2 cause by anaemia, methaemoglobin, CO poisoning– Do not stimulate peripheral
chemoreceptors
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Peripheral ChemoreceptorsWhen PO2 falls below 60–80
mm Hg– There is an increase in rate of
discharge of fibers from the receptors to RC
– ↑Rate and depth of respiration– ↑Alveolar ventilation
•Elimination of CO2
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Peripheral chemoreceptorsElimination of CO2
– Respiratory alkalosis • ↓H+ conc CSF• Inhibition of respiratory drive
Over the course of several days– Ionic pumps (pia matter, choroid
plexus)• Transfer HCO3
- from CSF to blood• CSF pH returns towards normal• Respiratory drive returns
May 8, 2023 Control of Respiration 38
Peripheral chemoreceptorsEffect of CO2 tensionElevation of CO2 tension also
– Stimulate peripheral chemoreceptors
– But most of effect of CO2 is on the central chemoreceptors
May 8, 2023 Control of Respiration 39
Peripheral chemoreceptorsEffect of H+ concentration↑in H+ conc
– Stimulate peripheral chemorecptors– Increase in ventilation
The increase in alveolar ventilation– ↓CO2 tension– pH return towards normal– Ventilatory drive tends to reduce
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Other receptors
Pulmonary stretch receptors– Lie within the walls of airways
They are stimulated by– Inflation of the lung
Initiate inspiratory inhibition– Termination of inspiration– Hering – Breuer reflex
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Other Receptors
Irritant receptors– Lie in large airways
• Between airway epithelial cells– Stimulated by
• Noxious gases, smoke, particulates in inhaled air
– Initiate reflex that stimulate• Coughing, bronchospasm, mucus secretion• Breath holding (apnoea)
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Other Receptors
J-receptors– Juxta-capillary – Located in the pulmonary
interstitium at the level of pulmonary capillaries
– Stimulated by the distension of pulmonary capillaries•Caused by ventricular failure,
emboli, chemicals
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Other Receptors
J-receptors– Initiate reflex that cause
• Rapid, shallow breathing, tachypnoeaNose & upper airway receptors
– Upper respiratory pathways contain receptors• Respond to mechanical, chemical stimuli
– Reflex initiated • Sneezing, coughing, bronchoconstriction
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Other Receptors
Joint & muscle receptors– Impulses from moving limbs
• Are believed to be part of stimuli for ventilation – Early stages of exercises
Baroreceptors– A rise in BP cause
• Reflex hypoventilation– A fall in BP cause
• Reflex hyperventilation
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