Control of Respiration
Neural Mechanisms
Chemical Mechanisms
19-Mar-16
Control of Respiration
1
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
19-Mar-16
Control of Respiration
2
Introduction
Other functions of respiration
include
– Phonation, singing, laughing,
whistling etc
In all these
– Extremely complicated
respiratory movements are
performed
– Require coordinated control
19-Mar-16
Control of Respiration
3
Neural Control of
Respiration
Cerebral
cortex
Corticospinal tract
Pons &
medulla
Reticulospinal tract
Spinal
cord
Respiratory
muscles
19-Mar-16
 Two neural
control
mechanisms
regulate
respiration
– One responsible
for voluntary
control
– The other one for
automatic control
Control of Respiration
4
Neural Control of
Respiration
Cerebral
cortex
Corticospinal tract
Pons &
medulla
Reticulospinal tract
 Voluntary
control system
– Located in
cerebral cortex
– Send impulses to
respiratory
muscles via
• Corticospinal
tracts (CST)
Spinal
cord
Respiratory
muscles
19-Mar-16
Control of Respiration
5
Control Systems for
Respiration
Cerebral
cortex
Corticospinal tract
Pons &
medulla
Reticulospinal tract
Spinal
cord
 Automatic system
– Located in pons
and medulla
oblongata
– Efferent output
from this system
to respiratory
muscles
• Located in spinal
cord close to CST
Respiratory
muscles
19-Mar-16
Control of Respiration
6
Control Systems for
Respiration
Cerebral
cortex
Corticospinal tract
Pons &
medulla
Reticulospinal tract
 Nerves serving
inspiration
converge in ventral
horns
– C3,4,5 (phrenic
nerve)
– External intercostal
motor neurons
 Fibres concerned
with expiration
Spinal
cord
Respiratory
muscles
19-Mar-16
– Converge on internal
intercostals motor
neurons
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Control Systems for
Respiration
Cerebral
cortex
Corticospinal tract
Pons &
medulla
 Reciprocal
activity
– Motor neurons to
expiratory
muscles
• Inhibited when
those to
inspiratory
muscles are
activated &vice
versa
Reticulospinal tract
Spinal
cord
Respiratory
muscles
19-Mar-16
Control of Respiration
8
Breathing Pattern
Electrical activity (diaphragm)
2 sec
3 sec
 During quite
breathing
 Inspiration is
brought about by
– Progressive
increase in
activation of
inspiratory muscles
 End of inspiration
associated with
– Rapid decrease in
excitation
19-Mar-16
Control of Respiration
9
Breathing Pattern
Electrical activity (diaphragm)
2 sec
3 sec
 The progressive
activation of
inspiratory muscle
cause
– Lungs to fill at
constant rate until
tidal vol reached
 End of inspiration
associated
19-Mar-16
– Rapid decrease in
excitation of
inspiratory muscles
• Expiration
occurs
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10
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
19-Mar-16
Control of Respiration
11
Respiratory Centers
Pneumotaxic
center
Apneustic
center
IX
DRG
DRG
X
VRG
XI
VRG
XII
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Control of Respiration
12
Respiratory Centers
Pneumotaxic
center
Apneustic
center
IX
DRG
X
XI
VRG
XII
19-Mar-16
 Composed of
several groups of
neurons
– Located
bilaterally in
• Medulla
oblongata
• Pons
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13
Respiratory Centers
Pneumotaxic
center
Apneustic
center
IX
DRG
X
XI
VRG
XII
19-Mar-16
 Three major
collection of
neurons
– Dorsal respiratory
group (DRG)
– Ventral respiratory
group (DRG)
– Pneumotaxic center
– ? Apneustic center
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14
Respiratory Centers
 Dorsal
respiratory group
(DRG)
IX
DRG
X
XI
VRG
XII
19-Mar-16
– Located on the
dorsal portion of
medulla
• In or near the
Nucleus of Tractus
Solitarius(NTS)
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Respiratory Centers
 NTS
IX
DRG
X
XI
VRG
XII
19-Mar-16
– Sensory terminal of
vagus &
glossopharyngeal
• Transmit sensory
signals from
– Peripheral
chemoreceptors
– Baroreceptors
– Receptors in the
lungs
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Respiratory Centers
 DRG made up
– Of I – neurons
IX
DRG
X
XI
VRG
XII
19-Mar-16
• Some project
monosynaptically
to phrenic nerve
motor neurons
(MN)
– Cause inspiration
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17
Respiratory Centers
 VRG
 Long column
extends through
IX
DRG
X
XI
VRG
XII
19-Mar-16
– Nucleus ambiguus
– Nucleus
retroambiguus in
the ventral
medulla
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18
Respiratory Centers
 VRG has both I & E
neurons
IX
DRG
X
XI
VRG
XII
19-Mar-16
– 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
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19
Generation of
Breathing Pattern
A
IX
DRG
X
XI
VRG
XII
D
19-Mar-16
 Rhythmic
respiratory
pattern
– Appear to be
initiated by the
• Rhythmic
discharges of
neurons in the
medulla and pons
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Generation of
Breathing Pattern
 Trans-section of brain
A
IX
DRG
X
XI
VRG
XII
– Below medulla
• Stops respiration
– Above the pons
• Automatic breathing
is still present
 Neurons in medulla &
pons
– Responsible for
generating the rhythmic
respiratory movements
D
19-Mar-16
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Generation of
Breathing Pattern
A
 The actual mechanism
responsible for
– Rhythmic respiratory
discharge not known
IX
DRG
X
XI
VRG
XII
D
19-Mar-16
 However,
– Group of pacemaker
neurons have been
identified
• Pre-Böttzinger
Complex
• Area between nucleus
ambiguus & lateral
reticular nucleus
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Pontine & vagal
Influence
 The spontaneous
IX
DRG
X
XI
VRG
XII
19-Mar-16
rhythmic discharges
of medullary
neurons is modified
by
– Neurons in the
pons
– Afferents in the
vagus from
receptors in the
airways and lungs
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Pontine & vagal
Influence
Pneumotaxic
center
IX
DRG
X
XI
VRG
XII
19-Mar-16
 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
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Pontine & vagal
Influence
Pneumotaxic
center
IX
DRG
X
XI
VRG
XII
19-Mar-16
 When this area is
damaged
– Respiration becomes
slower
– Tidal volume greater
 Pneumotaxic center
may play a role
– Switching
between
inspiration &
expiration
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Pontine & vagal
Influence
Pneumotaxic
center
Apneustic
center
IX
DRG
X
XI
VRG
XII
19-Mar-16
 Apneustic center
– Situated in lower
pons
 Send signals to DRG
– Prevent “switchingoff” of respiratory
ramp (increase
duration of
inspiration)
– Lungs become
completely filled with
air
Control of Respiration
26
Pontine & vagal
Influence
Pneumotaxic
center
 Apneustic center is
inhibited by
Apneustic
center
IX
DRG
X
XI
VRG
XII
– Vagus & pneumotaxic
center
 Vagotomy &
destruction of
pneumotaxic center
causes
– Prolonged period of
inspiration
• Apneusis
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Control of Respiration
27
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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Control of Respiration
28
Chemical Control
Types of receptors
– Central chemo-receptors
– Peripheral receptors
– Others
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Control of Respiration
29
Central
Chemoreceptors
 Chemosensitive
Chemosensitive
neurons
neurons
DRG
– Bilateral beneath
the ventral medulla
 Sensitive to
CO2 + H2O ⇌ H2CO3 ⇌ HCO3- + H+
19-Mar-16
changes in PCO2 &
H+
 H+ only important
direct stimulus
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Central
Chemoreceptors
 H+ crosses the blood-
brain –barrier (BBB)
very poorly
Chemosensitive
neurons
DRG
– Changes in H+ in
blood have less
immediate effect on
respiration
 CO2 diffuse easily
across BBB
CO2 + H2O ⇌ H2CO3 ⇌ HCO3- + H+
19-Mar-16
– It is then hydrated
and dissociates to H+
& HCO3-
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Central
Chemoreceptors
Chemosensitive
neurons
DRG
CO2 + H2O ⇌ H2CO3 ⇌ HCO3- + H+
19-Mar-16
 An increase CSF
CO2 causes
chemoreceptors
to stimulate
respiration
 A decrease CSF
CO2 causes
chemoreceptors
to inhibit
respiration
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Peripheral
Chemoreceptors
Located in the carotid & aortic
bodies
These receptors respond to
– Lowered arterial O2 tension
– Rise in arterial CO2 tension
– Increase in H+ conc in arterial
blood
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Control of Respiration
33
Peripheral
Chemoreceptors
Arterial 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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Control of Respiration
34
Peripheral
Chemoreceptors
Thus they monitor
–O2 tension rather than O2
content
• O2 cause by anaemia,
methaemoglobin, CO poisoning
– Do not stimulate peripheral
chemoreceptors
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Control of Respiration
35
Peripheral
Chemoreceptors
When 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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Control of Respiration
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Peripheral
chemoreceptors
 Elimination 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
19-Mar-16
Control of Respiration
37
Peripheral
chemoreceptors
Effect of CO2 tension
Elevation of CO2 tension also
– Stimulate peripheral
chemoreceptors
– But most of effect of CO2 is on
the central chemoreceptors
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Control of Respiration
38
Peripheral
chemoreceptors
 Effect 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
19-Mar-16
Control of Respiration
39
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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Control of Respiration
40
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)
19-Mar-16
Control of Respiration
41
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
19-Mar-16
Control of Respiration
42
Other Receptors
 J-receptors
– Initiate reflex that cause
• Rapid, shallow breathing, tachypnoea
 Nose & upper airway receptors
– Upper respiratory pathways contain
receptors
• Respond to mechanical, chemical stimuli
– Reflex initiated
• Sneezing, coughing, bronchoconstriction
19-Mar-16
Control of Respiration
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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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Control of Respiration
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