NROSCI-BIOSC-MSNBIO 1070-2070

Respiration 4October 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 respiratory-related 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• 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

A: pneumotaxic areaB: apneustic areaC: dorsal respiratory groupD: ventral respiratory group

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

• 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.

Black: Inhibitory White: Excitatory

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

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Medial Reticular Formation Neurons Mediate Vomiting

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 parasympathetically-mediated 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