CSB346 Lecture 8 – Airway and Pulmonary Reflexes (March 19, 2013)
Slide 2 – Central regulation of breathing
- The last two lectures talked about how the CNS and PNS detect chemical stimuli (e.g., CO2 and
O2) and how changes in those chemicals impact respiration.
- How do mechanical stimuli affect respiration? This is called airway or pulmonary reflexes. They
are not sensitive to changes in a chemical. How do airway and lung receptors affect the
respiratory network? How do upper airway muscles affect the respiratory network? It is a
mechanical message rather than a chemical message.
Slide 3 – Reflexive signals
- Airway reflexes encompass everything from the nostrils to the larynx. Anything below the larynx
is a pulmonary reflex. Breathing rhythm is generated by a network of neurons in the brainstem.
They control the motoneurons and muscles that allow thoracic expansion and contraction. This
affects the pressure changes that ultimately drive thoracic expansion and contraction (e.g.,
Slide 4 – Mechanical control of breathing
- Mechanoreceptor is like an elastic. If the mechanoreceptor is not being stretched, it is not being
activated. If the mechanoreceptor is being stretched, it affects how the mechanoreceptor would
send information back up to the brain. We are going to focus on the different types of
mechanoreceptors that are located within the lungs and the upper airways.
Slide 5 – Airway receptors
- Afferents are referring to the receptors that are doing the detection. There are a series of
afferents (e.g., receptors communicate their information via nerves to the CNS). There are two
sources of afferent pathways: lower airway and upper airway.
- These are some of the signals that the afferents can detect.
o Respiratory sensation (e.g., dyspnea)
o Intraluminar pressure (e.g., within the tube of the airway)
- In order to understand how reflexes are mediated, we need to think of the possible neural
pathways that go from the airways to the CNS.
o The carotid sinus nerve relays information from the CB to the brain.
o In terms of lung tissue and airway tissue, what are the neural pathways that get from
the sensory cells in those tissues to the brain? What are the afferent pathways?
Slide 6 – Pulmonary receptors
- The vagus nerve is the “super highway” of sensory information from the thoracic component of
your body. An enormous number of afferents in the lung tissue are relayed to the brain via the
vagus nerve. It is an important nerve in relaying information from the lungs to the brain.
- The sensory receptors in the airways within the lung have key roles in controlling breathing and
in various defenses. They get that information to the brain via the vagus nerve. The vagus nerve
plays a key role in the mechanical control of breathing.
- This shows where the vagus nerve is sitting. The vagus nerve is coming all along down the
external carotid artery. The vagus nerve communicates with all the vagal afferents sitting in the
lung. The vagus nerve has both descending and ascending projections. We are going to talk
about the ascending afferent projections. The right vagus nerve relays information largely from the right side. The left vagus nerve relays information from the left side. The vagus nerve is
carried up and it lands in the nodose ganglion.
Slide 7 – Pulmonary reflexes and the vagus nerve
- The vagus nerve has a whole bunch of branches coming off of it that are going to different
places. This shows you the various branches of the vagus nerve.
o We are going to talk about vagal afferents that are above the bifurcation. We are going
to primarily talk about the pulmonary branches that feed information from all the
receptors in the lungs. The vagus nerve has a whole bunch of branches coming into it
that are above the pulmonary branches (e.g., RLN, SLN).
o The dendrites for specialized receptors are sitting in the lung tissue, for example. Their
afferents go all the way up. The bodies for the cells are sitting up here in the nodose
ganglion. The specialized receptors (e.g., the dendrites) are sitting in the lung tissue. The
axons terminate primarily in the NTS. The NTS is a huge integration center for the
respiratory system. A lot of other receptors are sitting in various tissues all around. Their
afferents are being relayed through various nerves.
- Nerves of major importance that carry pulmonary afferents are the intrathoracic vagus (or the
pulmonary branch), but the RLN is also another major branch that makes up the vagus nerve.
These two types of nerves carry the afferent information from the trachea, larynx, and so on.
The RLN is taking most of the information up from all of the structures around here. The
pulmonary branch of the vagus is taking a lot of information from the lung. All of those branches
are carried in the vagus nerve. The cell bodies for all of those afferents are sitting in the nodose
o All the specialized receptors are here. Their dendrites go up the vagus nerve to the cell
body that makes them, which sits in the nodose ganglion. The axon goes up and
terminates in the NTS.
Slide 8 – The vagus nerve
- This is the airway within the lung. The cell body is sitting in the nodose ganglion. It sends its
information up into the NTS through the vagus nerve.
- The cell body is not the receptor. It is specialized dendrite of these nerve cells. The cell body is
sitting in the nodose ganglion.
- There are laryngeal and pharyngeal branches. The pharyngeal is taking sensory information from
the pharyngeal airspace. It is also relaying information up. It is part of the vagus nerve.
- This is a picture of a brainstem. All of the things coming in it are the actual branches coming into
the brainstem from all of the various sources. The white ones (#2) are the afferent inputs from
the vagus nerve. They are all terminating in the NTS.
Slide 9 – Pulmonary afferents in the vagus nerve
- The vagus nerve is important in modulating breathing. There are stretch receptors in the
airway and the lung tissue. The information from the pulmonary stretch receptors is thought to
be carried in the vagus nerve to the brain. If we do a vagotomy (e.g., cutting the vagus nerve),
you should see a profound change in breathing if it is relaying important information.
- This is the phrenic nerve that goes to the diaphragm. This is the hypoglossal nerve that goes to
This is when the vagus nerves are intact. When you adjust tracheal pressure (e.g., by sucking air out or pushing air into
the trachea), you can see that the tongue responds powerfully to the stimulus.
This indicates the changes in airway pressure are detected by the tongue. The
diaphragm doesn’t do too much. This is showing you that changes in tracheal
pressure are sensed by the tongue.
Then we vagotomize the vagus nerve. When you remove the influence of the
vagus nerve, both upper airway and phrenic activity change profoundly. It goes
up in amplitude and breathing is slower. The breathing amplitude and frequency
- There is some piece of information being transmitted to the brain from the lungs that is
changing the pattern and timing of breathing. When the vagus nerve is removed, it inhibits
breathing. The inhibition makes it much higher in overall amplitude. There is something that
slows breathing down in the vagus nerve.
o This is the Hering-Breuer reflex.
Slide 10 – The Breur-Hering reflex
- The Breuer-Hering reflex is that the vagus nerve is an important part of the respiratory system.
The Breuer-Hering reflex is telling you that distending the lung tissue has a profound effect on
- This is intratracheal pressure. They put a pressure transducer into the throat of a dog. They
measured the changes in pressure in the throat. As you breathe in, pressure drops inside the
airway relative to the atmosphere. As you breathe out, pressure increases. This is the pressure
gradient. As your chest expands, the pressure drops. The drop in pressure generates the airflow
that moves into the lung. As your chest deflates, the pressure increases. This causes the air to
move out of the lung.
o You can measure pressure inside the throat and the chest. This gives you an index of
inspiration and expiration.
o When there is no pressure, the dog is inspiring and expiring. The deflections represent
the pressure due to inspiration. Then there is a big change in pressure. They kept the
dog’s airway closed. They disabled the dog’s ability to deflate its lungs. The deflections
stopped. There was no pressure deflection. The dog stopped breathing. When they
change the pressure, the dog doesn’t try to breathe. Then the dog takes a big breath.
Then it doesn’t breathe. Then it takes another big breath. Then they let the pressure fall
back to normal and the dog resumes to breathing normally.
o The change in pressure is being sensed by the blood pressure. Every deflection is a
heartbeat. When they clamp the airway, blood pressure drops. This is a standard
o The increase is experimentally induced changes in pressure. When the pressure goes up,
the deflections have stopped. This means the dog is not trying to breathe in. What is the
point of breathing in when the lungs are maximally inflated?
- What is causing the Breuer-Hering reflex? Why would the dog stop breathing? If they inflate the
lungs, why isn’t the brain trying to send any information to breathe? The vagus nerves go to the
lung. The vagus nerve is important in mediating the Breuer-Hering reflex.
o They cut both of the vagus nerves. They did the same thing. The dog is breathing. Then
they increase the pressure like before. The dog continues to breathe. Then they drop
the pressure down and breathing is normal.
o When the vagus nerve is cut and the pressure goes up, the dog keeps breathing. - This is evidence that there is something special when you keep the lungs inflated. The brain
recognizes it because the dog doesn’t try to breathe. When they cut the vagus nerve, the brain
doesn’t recognize that the lungs are inflated and they keep sending the respiratory signal down
to the phrenic nerve.
o The vagus nerve is carrying the information that tells the dog’s CNS that the lung is
either inflated or deflated. The vagus nerve is important because when you get rid of it,
the dog continues to breathe even though the intratracheal pressure has been
- This tells us that mechanical deformation of the lungs affects the way the CNS sends respiratory
signals to the muscles (e.g., diaphragm, airway). If you change pressure in the lung, you get a
change in breathing. When you get rid of the vagus nerve, that response goes away. Therefore,
the vagus nerve must be mediating that response.
- What are the things that are doing the detecting to cause this Breuer-Hering reflex?
Slide 11 – Types of pulmonary receptors
- There are pulmonary receptors in the chest that are sending information to the brain. There are
different types of pulmonary receptors.
- SAR and RAR are mylinated, which means they send information quickly to the brain. Broncho-
pulmonary C fibres are unmylinated, which means they send information slowly to the brain.
o Mylinated neurons send information much more quickly than unmylinated.
Slide 12 – Pulmonary afferents and their associated reflexes
- When the broncho-pulmonary C fibres are stimulated, they have a variety of reflex responses.
- Airway mucus secretion is a long-term type of response. Mucus secretion isn’t spontaneously
produced and secreted. The unmylinated nature of broncho-pulmonary C fibres means that they
don’t transmit their information as quickly to the brain. This is perhaps why these are
unmylinated because getting mucus to be secreted isn’t something that takes split second time
resolution. It takes some time to do it.
- These fibres can trigger a range of different types of responses. These elicit a range of
behaviours, which depend on the circumstance in which these receptors are being activated.
There are a range of responses because there are two different stimuli. There are also different
types of edema and different types of irritants.
Slide 13 – Pulmonary afferents and their associated reflexes
- Mechanical deformation is important. Edema affects the airway consistency.
- These reflexes depend on a variety of things and conditions. Just remember that when you
stimulate these receptors, you get a variety of reflex responses. I do not expect you to
understand why you get cough, or augmented inspiration.
Slide 14 – Pulmonary afferents and their associated reflexes
- SARs are quite important. When the dog’s airway was inflated, there was no more inspiration
occurring. SARs stop the brain from trying to inspire and inflate the lungs. Expiratory
prolongation is not breathing in.
- The airways can be distended by inflation or some other process. We will only talk about lung
inflation causing airway distension.
Slide 15 – Activity of pulmonary receptors
- If you could record the activity of these receptors, what would it look like? - If you look at the discharge from the airway sensors (e.g., the receptors), you are recording the
nerves that are going up to the brain in the form of action potentials.
o You are recording the nerve that is sending information from the SAR in the airway
smooth muscle. What do the action potentials look like in response to a change in
o The top trace is showing how airway pressure is changing. The bottom trace is showing
how a SAR responds to the change in airway pressure.
o When airway pressure is increased (e.g., the lungs are being distended), there is an
immediate response in the increase in the number of action potentials per unit of time.
They stay fairly consistent. There is a burst of lots of APs. They still continue to fire but it
slowly decreases to fewer action potentials per unit of time.
o The stimulus is constant, but the receptors are slowly adapting by reducing the number
of action potentials in response to the constant stimulus.
o You cause an increase in airway pressure. Before there is an increase in airway pressure,
the RARs are not discharging APs. When pressure goes up, they immediately sense that
and they fire rapidly. They seem to stop firing APs. They rapidly adapt to that stimulus.
o This is the C-fiber receptors. This is the discharge of the C-fiber receptTr. P is the
pressure in the tracheal area, which is going up and down. The C-fiber receptor is not
firing in any temporal correlation with tracheal pressure. These receptors aren’t
necessarily listening to changes in the pressure. They are more interested in airway
edema and chemical irritants. It makes sense that these receptors aren’t responding to
- RAR and SAR are much more responsive to changes in airway pressure.
Slide 16 – Activity of pulmonary receptors
- This is a change in pressure associated with ventilation (left). This is an artificially induced
change in pressure (right).
- We are looking at sensory discharge from the SAR and the RAR. This figure demonstrates that
increased lung volume activate both of the receptors. This is a natural increase in lung volume.
These are increases in which air was forced into the lung. This is a natural change in pressure
associated with inspiration and expiration (left). This is an artificial increase in pressure (right).
- Both the SAR and the RAR are listening to the natural changes in airway pressure associated
with inspiration and expiration.
- Top (RAR)
o When there is inspiration, airway pressure increases. The RAR immediately begins to
fire. It stops listening to the pressure change. It largely stops firing. When the airway
pressure increases again, the RAR increase their activity but they stop firing even before
the pressure decreases.
o By the artificial stimulus, you artificially keep the lung pressure higher by pumping air
into the face by a mask. You can see that the RAR fire action potentials but then they
rapidly adapt and stop firing APs even though the pressure is maintained.
o They are rapidly adapting to the constant pressure change.
- Bottom (SAR)
o When pressure is increased and decreased across the natural respiratory cycle, look at
the firing pattern of the SAR. They are always firing action potentials in comparison to RAR. They are increasing their firing during the increase in pressure associated with a
natural inspiration. They don’t adapt too much. They are slowly adapting. They adapt
somewhat. They don’t change much across the respiratory cycle. They are very closely
listening to the changes in pressure associated with airway distension.
o When the pressure is increased, the SAR increases their firing frequency. This suggests
that they are increasing their firing frequency because of an increase in pressure. They
don’t change their firing frequency even though the pressure stays constant.
- This demonstrates that both the RAR and SAR are consistently active across the respiratory
cycle. The SARs are firing more with increased pressure, but they still fire when the lungs are
deflated. The RARs don’t seem to have too much activity before the increase in pressure, but
they do fire across the respiratory cycle during inspiration and expiration. The SARs are much
more “excitable”. The SARs are listening much more carefully to changes in pressure. The SARs
are active during inspiration and expiration, but they are more active during inspiration because
they are listening to the increase in pressure.
Slide 17 – Stretch receptors P-cells
- How do these stretch receptors communicate with the brain? When you activate them, you
have a series of respiratory reflexes. When these receptors are activated, the brain has to
change breathing. These receptors are somehow communicating with the CNS and presumably
the RRG centers to mediate those responses in breathing. How do they get that information to
- We are going to focus on the SARs because they are constantly listening to changes in pressure
more than the RARs. How do they get their information from the lung to the RRG to elicit
changes in breathing?
o The SARs are in the lung airway tissue. When they are stimulated, inspiration is
terminated or expiration is prolonged. What is the evidence?
- There are several steps. The first step is P-cells (e.g., pump cells).
o They recorded cells in the area of the NTS and noticed that these cells would fire in
relation to the pump.
Most of these experiments are done in ventilated cats.
o They would be recording the respiratory cells in the DRG or the VRG, and they found a
group of cells that seem to be listening to the pump when the cat’s lungs were inflating,
rather than listening to the activity of the phrenic nerve that generates inspiration.
When the cat is being ventilated, the phrenic nerve can fire independently of
the pump. The phrenic nerve could be firing, and the physical inflation and
deflation of the lungs doesn’t have to be following exactly. This is because the
vagus nerve that is relaying a lot of information to the brain about the status of
the lung has been cut. You have a dissociation of the signals that the brain is
generating and the physical/mechanical responses that the lungs are producing.
o They noticed that P-cells would be firing in relation to when the pump was active, but
not to the phrenic nerve that innervates the diaphragm.
The second trace is the activity of the phrenic nerve. The third trace is the
recording a PSR. The first trace is the activity of the pump cell. There is a period
where the pump cell doesn’t fire, but the phrenic nerve does.
The phrenic nerve is not driving the expression of the pump cell. There is some
other stimulus that is causing the pump cell to be activated. It was thought that
the inflation of the lung is causing this response. - Why are the pump cells not firing with inspiration? Why are the pump cells firing with lung
inflation? The lungs are inflated because the ventilator is inflating the cat’s lungs. The cat is not
able to inflate its own lungs because the phrenic nerves are cut from the diaphragm.
o Maybe the SARs are driving the activity of the pump cells, which in turn tell the RRG
system when to drive the phrenic nerve.
Slide 18 – Projections of P-cells
- How do the SARs located in the lung tissue get their information to the brain? We think it is
the pump cells. The pump cells are sitting in the NTS. This is not part of the classic RRG system of
the VRG/DRG/PRG. How do the pump cells get their information to the pontine and medullar
brain structures that physically generate respiration?
o The NTS is a giant relay station. A lot of sensory information from the vagal nerve
afferents terminates in the brain at the NTS. Then