NROSCI-BIOSC-MSNBIO 10702070
Respiration 4
October 19, 2015
Control of Respiratory Muscle Contractions
• The pattern of discharges
illustrated to the left can
be recorded from
respiratory muscles
during breathing. Note
the shape of the
responses: they are
augmenting.
• The diaphragm is innervated by axons of
motoneurons located in the C3-C5 segments of the
spinal cord. These motoneuron axons travel as a
spinal nerve, the phrenic nerve, to reach the
diaphragm.
Control of Respiratory Muscle Contractions
• The diaphragm differs from most skeletal muscles in
the body, in that it possesses very few muscle
spindles. As such the diaphragm is incapable of
detecting its own length.
• The intercostal muscles are innervated by thoracic
motoneurons, whereas the abdominal muscles are
innervated by thoracic and lumbar motoneurons.
The motoneuron axons leave the spinal cord as many
segmental spinal nerves. The abdominal and
intercostal muscles have a “typical” number of
spindles.
Upper Airway Muscles
• Resistance in the upper airway is controlled by pharyngeal
and laryngeal muscles and tongue musculature. Laryngeal
and pharyngeal muscles are innervated by brainstem
motoneurons whose axons course in cranial nerves IX and X.
Tongue musculature is innervated by the hypoglossal nerve.
• The muscles of the upper airway are rhythmically active
during the respiratory cycle. Many of these muscles have
inspiratory activity, and serve to open the upper airway
during diaphragm contraction. For example, you protrude
your tongue during inspiration to help open the airway. The
vocal cords must also be retracted during inspiration.
• The expiratory upper airway muscles are involved in
regulating the rate of airflow during expiration. This
“braking” effect is needed to assure that air is not expelled
too forcefully.
Swallowing
• Swallowing is a behavior that requires the
coordinated actions of the upper airway respiratory
muscles.
• Recall that both the trachea and esophagus make
connections with the pharynx. During swallowing,
it is essential that ingested materials do not move
into the larynx and trachea. The larynx closes
tightly, and some pharyngeal muscles also contract
to divert materials away from the larynx.
• Respiration must be curtailed during swallowing (as
the upper airway is closed off). At the same time,
part of the diaphragm surrounding the esophagus is
actively inhibited to assure that food can pass into
the stomach.
Coughing
• A cough begins with an inspiration due to
contraction of the diaphragm.
• Next, the compressive phase begins, in which the
diaphragm continues to contract, but the expiratory
muscles also contract. The larynx is closed during
this stage.
• The upper airway then opens, inspiration
terminates, and a powerful expiration occurs
(because expiration began while the larynx was
closed).
• This is a very different pattern of respiratory muscle
activity than during normal breathing, as the
inspiratory and expiratory muscles are contracting
together, and in a coordinated fashion.
Speech
• Speech is also accomplished through the respiratory
system.
• During speech, the laryngeal muscles stretch and
position the vocal cords in the larynx so that they
will vibrate appropriately when air is pushed over
them.
• Speech only occurs during expiration, so the brain
must appropriately time this process (as you aren’t
inspiring while it occurs).
• During speech (particularly when the volume is
loud), the expiratory muscles (especially the
abdominal muscles) contract powerfully to push air
over the vocal cords.
Vomiting
• Vomiting is accomplished through the simultaneous
contraction of the diaphragm and abdominal
muscles. The contraction of both of these muscle
groups places pressure on the stomach, which
causes the gastric contents to be ejected.
Posturally-Related
Effects
• The respiratory
muscles
additionally
participate in
postural control
and the generation
of movement. At
least part of the
changes in
respiratory muscle
activity during
alterations in
posture is due to
the vestibular
system.
The Medullary Respiratory
Groups
• The contractions of the
respiratory muscles are
controlled by two
groups of neurons in
the caudal brainstem:
the dorsal and ventral
respiratory groups
The Medullary Respiratory
Groups
• Neurons that relay the
“augmenting” commands to
inspiratory muscles are
located in the dorsal and
ventral respiratory groups,
whereas the expiratory
command neurons are
located only in the ventral
respiratory group.
Pontine Respiratory Neurons
• Some pontine neurons, located near the
parabrachial nucleus, also have respiratoryrelated activity.
• However, these pontine respiratory neurons
do not project to the spinal cord.
• It is believed that the pontine respiratory
neurons help to shape the firing pattern of
the medullary respiratory neurons, although
they are not required for respiration to
occur.
Pontine Respiratory Neurons
A: pneumotaxic area
B: apneustic area
C: dorsal respiratory group
D: ventral respiratory group
• The “pneumotaxic” area in
the rostral pons inhibits the
MRGs
• The “apneustic” area in the
caudal pons stimulates
MRGs
• These accessory respiratory
centers control the depth
and frequency of breathing
in accordance with signals
from higher brain regions
Respiratory Rhythm Generation
• The essential circuitry for establishing the respiratory rhythm
is located in the rostral portion of the ventral respiratory
group. Lesions of this small area abolish the rhythmic
respiratory activity, and a small slice 1 mm thick containing
the rostral ventral respiratory group retains respiratory
rhythmicity.
Respiratory Rhythm Generation
•
Only a small fraction of neurons in
the dorsal and ventral respiratory
groups have augmenting discharge
patterns and project to the spinal
cord. Some neurons have
decrementing discharge patterns,
others fire constantly throughout
inspiration, and “phase-spanning’
neurons fire between inspiration
and expiration.The connectivity of
the respiratory neurons in
establishing the respiratory rhythm
has been the subject of many
electro-physiological studies.
Models that account for the
respiratory rhythm have been
established from these data.
Respiratory Rhythm Generation
Black: Inhibitory
White: Excitatory
•
Note: Excitatory E-AUG (bulbospinal) cells
are not illustrated, as they are not part of
the rhythm-generating network, but receive
input from that network.
Respiratory Rhythm Generation
•
The practicality of central pattern
generators is evidenced by Ondine’s
curse
•
Patients with this extremely rare
disorder lack the PHOX2B gene
•
As a result, their respiratory pattern
generator does not develop
•
The patients can breath voluntarily, but
not automatically
•
Patients with Ondine’s curse require a
tracheostomy and artificial respiration
to survive, as they fail to breath upon
falling asleep
Other Respiratory Neurons
• Although the dorsal and ventral respiratory
groups are fundamentally responsible for
generating the respiratory rhythm and
imparting it on respiratory motoneurons,
their activity cannot explain all behaviors
involving respiratory muscles.
• During vomiting, for example, a majority of
brainstem respiratory group neurons is
inhibited. Thus, during vomiting, breathing
stops and a different population of neurons
than is responsible for producing breathing
activates respiratory motoneurons.
Use of Rabies Virus to Trace Neural Pathways
that Regulate Diaphragm Activity in the Cat
Other Respiratory Neurons
In addition to respiratory group neurons, cells in the medial
medullary reticular formation and vestibular nuclei project to
respiratory motoneurons
Medial Reticular Formation
Neurons Mediate Vomiting
21
Reflex Control of
Respiration
The Hering-Breuer Inflation
Reflex
• A number of stretch receptors exist within the bronchi and
bronchiole smooth muscle. When activated by lung
overinflation, these afferents powerfully inhibit neurons in the
dorsal and ventral respiratory groups. This Hering-Breuer
Inflation reflex assures that the lungs do not overinflate to the
point of being damaged.
• As noted earlier, the diaphragm contains few muscle spindles.
However, other respiratory muscles, including the intercostal
muscles, contain large numbers of spindles. It seems likely
that spindle inputs from these respiratory muscles would
contribute to the Hering-Breuer reflex, through actions at both
the brainstem and spinal level. However, these effects have
not been well described.
Chemical Control of Respiration
• Hydrogen ion would perhaps be the best
agent at stimulating ventral medullary
chemoreceptors if it could reach the
brainstem effectively. However, the
diffusion of this ion is limited by the
blood-brain barrier.
• In contrast, carbon dioxide can readily
enter the cerebrospinal fluid, where it
reacts with water to form carbonic
acid. The released H+ then stimulates
the ventral medullary chemoreceptors.
Because the cerebrospinal fluid has
little protein buffer, an increase in
PCO2 in the blood rapidly induces an
acidification of CSF.
Ventral Surface Chemoreceptors
• The ventral surface
chemoreceptors adapt to an
increase in PCO2 that lasts for
more than about a day (more
on this next lecture).
• When ventilation is
insufficient, bicarbonate
increases in the blood, partly
through the actions of the
kidney. As a result,
bicarbonate will accumulate in
CSF and counteract the
hydrogen ion.
Peripheral Chemoreceptors
• Oxygen levels in the blood are
monitored by receptors
located in the carotid body
and aortic bodies.
• The afferents of carotid body
chemoreceptors pass through
Hering’s nerves to Cranial
Nerve IX, and then to nucleus
tractus solitarius.
• Afferents from the aortic
bodies pass through the vagus
nerve to terminate in nucleus
tractus solitarius.
Peripheral Chemoreceptors
• PO2 must change considerably
before peripheral
chemoreceptors respond to
this stimulus.
• These receptors also show
sensitivity for CO2 and H+, and
under most conditions these
agents control peripheral
chemoreceptor firing.
• If PO2 falls considerably, the
decreased blood oxygen
induces a strong increase in
peripheral chemoreceptor
afferent firing.
Chemical Control of Respiration
• The diagram to
the left
summarizes the
effects of pH,
PCO2, and PO2 on
ventilation.
Sneezing
• As discussed previously, sneezing is a
specialized protective reflex for the
respiratory system.
• This response can be triggered by the
stimulation of pulmonary irritant
receptors in the trachea, bronchi, and
bronchioles.
• Stimulation of these receptors may
also induce a parasympatheticallymediated bronchoconstriction.
J-Receptors
• A few sensory nerve endings are in
juxtaposition with pulmonary capillaries,
and are referred to as J-receptors.
• They are stimulated when the pulmonary
capillaries are filled with blood.
• However the functional role of these
receptors is unknown.
Cheyne-Stokes Breathing
• Cheyne-Stokes breathing is a condition in which the respiratory
amplitude waxes and wanes over 40-60 sec cycles.
• Basically, it is a maladaptive response in which central
chemoreceptors have an unusually large effect on ventilation.
• Cheyne-Stokes breathing is very common in patients with
cardiac failure, in which a long time is required for blood to
travel from the lungs to the brain.
• This condition can also occur during brainstem damage, in
which chemoreceptors generate atypically large responses.
Exercise & Respiration
• During exercise, the diffusing
capacity for carbon dioxide and
oxygen in the lungs increases
tremendously.
• This is due to the fact that:
➡ More pulmonary capillaries are
patent because of the higher
arterial pressure.
➡ There is a “matching” between
enhanced ventilation and blood
flow to the alveolus.
Exercise & Respiration
• During exercise, O2
consumption and CO2 formation
can increase 20-fold. It is
tempting to account for the
enhancement of ventilation by
chemoreceptor reflexes. This
cannot be the case, however,
as the matching between
oxygen usage and total
ventilation is too good.
• There is evidence to suggest that during exercise, commands
from higher centers are mainly responsible for producing
enhanced ventilation. Inputs from receptors in limbs muscles
may be used to gauge the extent of exercise that is taking
place, so that appropriate ventilatory matching can occur.
Exercise & Respiration