Hello and welcome to this lecture for 4610. This lecture on the control of breathing is coming after the three lectures we did on the ventilation and exercise. So for the past lectures, we've seen how the ventilation increases, how the ventilation follows the intensity of exercise, and how the ventilation follows the carbon dioxide, also production mostly. We've seen the different reasons why we increase the ventilation, the metabolic reason, the mechanical reason.
We also, the previous lecture was just about the kinetics of the ventilation with the phase 1, the phase 2 and the phase 3. With the different reasons why we had the phase 1, which was more cardio-dynamic, why we had the phase 2 and why we had the phase 3. Now we're going to start actually... new chapter because we never really talk about what control the ventilation what makes physically really able to increase the ventilation or decrease the motivation and that's a pretty complex system because when you think about it the respiratory system as well as other system in your body like the skeletal muscle, but there are not many that are able actually to have a voluntary control. By voluntary, I mean that if you decide to change your ventilation, you can do it. For example, if I ask you to hold your breath, you could just hold your breath for as long as you can. Or I can also ask you to increase the ventilation, and you can increase the ventilation, you can increase the amplitude, the depth of your ventilation up and down.
or you can increase the frequency of the ventilation, how quickly you can breathe. So there's a lot of different ways where you can control the ventilation. If you compare this to other systems like the cardiovascular system, because we often compare or study the cardiovascular system with the respiratory system, if you do that then you can see for the cardiovascular system there is no voluntary control.
You cannot increase or decrease the heart rate by yourself as easily as you could do with the ventilation. So this lecture is really about that aspect, what can control your breathing. So we're going to start here with a simple graph that I think you know and you understand.
You've heard about the ventilation at rest before. So we're going to start here, which is... Starting with a quiet breathing, a ventilation at rest. When you are quiet, the inspiration, especially the signal coming from the inspiratory area, is active.
What I mean by active is that for the inspiration, you need to contract your diaphragm. By contracting your diaphragm, you're going to lower the diaphragm. And by lowering the diaphragm, you increase the volume of the chest.
By gradient of pressure, there is an inverse relationship between volume and pressure. So by gradient of pressure, you basically can inhale. There is air coming from outside into the respiratory system, into your lungs.
So you have a normal, quiet inspiration. At rest, your expiration is known as inactive here or passive expiration. And...
you just need to actually stop the inspiration for the elastic recall of the lungs to actually retract and then change the volume of your lungs again. By decreasing the volume of the lungs then you increase the pressure and by gradient of pressure the air comes out. So this is a passive quiet expiration that doesn't require any energy actually. Now, when you talk about exercise, it's a different story. Both the inspiration and the expression are active.
I'm sure you learn about this in other classes, in basic exercise physiology classes. But you see here on this graph, it's called the labored breathing, but for the purpose of this lecture, we'll obviously reference that to exercise. So, during exercise, what's happening?
Your inspiration here is obviously still active, but it's much more active. There are not only the diaphragm, but there are many other muscles, all of the other accessory muscles like the intercostal muscles, the sternocleidomastoid muscles, back muscles, and so on. They can be used for a more thoughtful inspiration.
So at the end the volume is more important and you can also increase the frequency. During exercise the expiration is also active. One of the most important muscles you're going to be able to use for an active expiration is going to be your abs.
So you're going to contract the abs and push the diaphragm up, increase the pressure inside your lungs and being able to have a complete forceful expiration. That's something I'm assuming you've learned before. But I would like for you to really pay attention to that particular arrow here, that particular link. So here you can see that during an active expiration, during exercise, it's actually the aspiratory centers, the aspiratory areas that are going to be able to control the expiratory centers. It's because you have an active expiration.
and an extra stimulation for the inspiratory system that you will stimulate also the expiratory system. We'll see later on, but there is a complete control actually of the expiratory system or the expiratory process by the inspiratory. So we'll develop that actually later on, but I would like you to keep this in mind because that's important. Okay, so what are we talking when we talk about control of breathing and what exactly can make your respiratory muscle being active to produce the volumes and to produce the pressure?
So the first thing we need to talk about is this idea of respiratory centers. There are two main respiratory centers. Here on this graph it says the medulla, but there's also...
the pons. P-O-N-S. I will describe this later.
So this is in your brain. The medulla and the pons are on top of your spinal cord. It's actually at the base of the brain. And it's between the cortex, between the higher centers of your brain and the spinal cord. So it's the perfect location for having respiratory centers.
where you can receive information from other parts of the body and transmit this information directly to your diaphragm, directly to other respiratory muscles and create the tidal volume and create the frequency. By controlling the volume and the frequency, you actually control the whole breathing pattern. So volume and frequency is what you need to control to increase the ventilation, especially during the exercise.
But if we add only this... a brain that controls the respiratory center. We would be unable to increase the ventilation for any other purposes than being voluntary, saying okay I need to increase the ventilation. And obviously that's not what's happening.
So there are many different feedbacks. Let me show you the most important. The higher centers of your brain, the motor cortex, can actually send feedbacks to the respiratory centers and that's called the central command.
Central because it's coming directly from your brain. And we'll see a little bit of that but not that much because this central command is actually not the most important for the respiration at least of what we are interested in which is the exercise. So let me just show you all of them quickly and I'll show you what's...
is the most important. So here is the most important. Number one.
and by far actually are the central chemoreceptors. Maybe 80% or maybe 70% depending on the literature, but 70% of the control of the ventilation is coming from the central chemoreceptors. So what are they? Well, we'll define and develop really a lot of central chemoreceptors and other receptors, so don't worry too much, but the central chemoreceptors are in your brain. And they are chemoreceptors, so they are receptors sensitive to changing chemicals.
And what type of chemicals can make those receptors active or stimulated? Two, the carbon dioxide and your hydrogen ions. But you know that those two are actually linked, because the carbon dioxide and the hydrogen ions are also composing your buffering system.
Right? So, We'll see how, but it's actually the hydrogen ions themselves that will be able to stimulate those central chemoreceptors. So keep in mind that the most important that send feedback to the respiratory centers to control the ventilation are actually central chemoreceptors sensitive mostly to change of pH and hydrogen ions. The number two, maybe for 20% of the...
the control of the ventilation. So you see between the central chemo receptors and the peripheral chemo receptors, you have almost 90% of the control here already. 20% are those peripheral chemo receptors.
So they are also receptor sensitive to change in chemicals, but those ones are peripheral. So you have two types of chemo receptors, two that are in the carotid bodies. Okay, so.
at the bifurcation of the carotids just before the carotids split into and go through your brain. Okay, so that's where the carotid bodies are and it's very tiny organs, clusters of cells that are very concentrated, very dense cells that are right there at the carotid. And we have another spot also has peripheral chemoreceptors that is close to the aorta.
right outside of the heart when you have a lot of blood that goes into the heart. So all of this is done by mistake. The peripheral tumor receptors being at the carotid bodies and the aorta by this very too specific location.
Within few seconds, actually less than a minute, those carotid bodies and those peripheral tumor receptors are going to be able to sense and monitor the concentration of gas from your whole body because the blood is passing through the carotid and is passing through the aorta very quickly and it allows you to monitor your five or six liters of blood within less than a minute. The carotid bodies are the most important, so around 90%. of the role of the peripheral chemoreceptors, of the function of the peripheral chemoreceptors, are coming from the carotid bodies. So make sure you understand what I'm saying here. The carotid bodies represent 90% of the peripheral chemoreceptors'work, but the peripheral chemoreceptors as a whole represent 20% of the whole control of ventilation, and thus...
feedbacks here that comes back to the respiratory centers. One thing that you also need to keep in mind for those peripheral chemoreceptors or cartilage bodies is that they are sensitive to mostly oxygen. So if I remove this, you see here they are sensitive mostly to a decrease of arterial partial pressure of oxygen. This is their main stimulation. But also.
sensitive to hydrogen ions and carbon dioxide, but really not in the same way as oxygen. So if you want, oxygen can really increase, can really stimulate the pyrophonic receptors or actually decrease their activity, while hydrogen ions, so your pH and carbon dioxide can modulate the response of the pyrophonic receptors depending on the oxygen. So you always need... the stimulation from the oxygen for the peripheral chemoreceptors. So that's why those two here, central here and peripheral chemoreceptors, are very important because the central chemoreceptors are responsible for hydrogen ions and carbon dioxide and the peripheral chemoreceptors are responsible for oxygen.
You see other receptors. So here I would say number three might be the receptors that we have at the muscle level, at the skeletal muscle level. So when you exercise, let's say you bike, you run, the legs muscles are going also to be able to send feedbacks to the respiratory centers to control the ventilation. Those receptors are mostly mechanoreceptors. So you have them here, the mechanoreceptors.
So these are receptors that are sensitive to change in tension and stretching. So when you mechanically move these receptors, they will send a feedback to the respiratory centers, and they will increase or decrease the ventilation. They can actually do both, but most of the time they actually have...
are more of a defense mechanism that allow for a decrease of the respiratory symptoms when you stimulate the mechanoreceptors too much. It's a defense mechanism that reduces the ventilation basically. Number four is certainly between the hypothalamus and the lungs.
So I put them together, the hypothalamus and especially with the temperature receptors that can increase or decrease the ventilation. So for example, when it's cold, you increase the ventilation to increase the mechanical term regulation or vice versa. When it's hot, you have also an effect on the ventilation.
In your lungs here, you have a different type of receptors, stretch receptors for example. Some of them are actually pretty important. like the stretch receptors that are responsible for the earring-brewer reflex, which is a defense reflex on the lungs actually. When you over-inflate the lungs, then they can reduce the size or they reduce the volume of the aspiration. So those receptors can also send signals to the respiratory centers.
We'll talk about those receptors a little bit, but not that much. focused mostly on the central and the peripheral chemo centers. Okay, so you get the idea.
You have a main command, main direction here from the respiratory centers to the respiratory muscle. And then all around it, coming from all over the place in your body, you have different sensors that will send feedback to those respiratory centers and modulate, modify your ventilation. This next graph is actually the same thing I just showed you before, except that it's a little bit more illustrated with drawings. So here, if you look at this whole thing here, it's the medulla and the pons. So it's not really separated on this graph, but this would be the medulla, this would be the pons on top.
And both of those represent together. the respiratory centers. So these respiratory centers you see here, you say it's misleading, when you look at the graph here it's actually at the base here of the brain because if you look at the bottom of the medulla here it's actually your spinal cord here so it's really at the base of your brain. The respiratory centers will receive All of the feedbacks that I mentioned before, the central chemoreceptors, the peripheral chemoreceptors, sensitive to oxygen, the central chemoreceptors sensitive to carbon dioxide and hydrogen ions, other receptors like the stretch receptors in your lungs or the muscle receptors that I mentioned before.
Some of the information you have here on top of the other graph you had before is actually the the direction of those feedbacks a little bit. So you see here, irritant receptors, stretch receptors are negative feedbacks, so they can stop the ventilation. Others are more positive feedbacks here.
But this is not as straightforward as that. You'll see when we look at studies and articles and science behind this, those receptors can actually be positive and negatives. Most of the case, most of the time. Maybe not do stretch receptors, but most of the other ones can be.
So let's see, we're going to start with just a very brief presentation, anatomical presentation of the respiratory centers. Just to show you what it is, I will not ask you to memorize anything about the anatomy really of the pons and the medulla, but it will help you to understand what I'm talking about after. So and to really see how amazing actually the system is when you think about it. and how the system and how your physiology is organized. So here, maybe on this graph on top, you can better see, you have a better idea of where the pons and the medulla are.
And again, if you understand the anatomy because of the physiology, if you understand the anatomy because of the function, then you can understand that the pons and the medulla are at the base of the brain because they receive information from the higher brain center. So this part here of the brain, the cortex, and all of this can send information to it, descending information, and the hypothalamus, like I mentioned before. They can also receive information from any other part of the body, so they are in contact with the spinal cord. And the role of those two parts, the pons and the medulla, the respiratory centers, is actually to send feedbacks to the rest of the body. to the muscle, the diaphragm, the abs and so on.
So they are right there at the spinal cord to send action potential and to send information. You can see here on this graph that this is not only the respiratory system. So the medulla and the pons are going to be a very important part for many other things, for the cardiovascular system, for your liver, for your eyes, for a lot of different things. But will focus obviously for the purpose of this class to only the respiratory system. So let's talk about the medulla.
The medulla is the inferior, the bottom part of the respiratory centers, which actually become the spinal cord. So it's actually on top of the spinal cord and allows for the communication between the brain and the spinal cord. The role of the medulla And that's really what I would like you to remember.
Okay, this is really the techo method and the important part on the medulla. Is to evaluate and prioritize neural signals. So let me give you an example for you to maybe better understand what I mean by evaluate and prioritize neural signals.
It's actually a pretty complex mechanism. So if in the example I can give you is if you ask somebody to hold their breath. So they hold their breath and then obviously after a minute, after two minutes or whatever time it would take for this particular individual to have the need to start to breathe again. So at one point you need to stop holding your breath and you need to breathe again. when you want to ask if you ask somebody to hold their breath it's the hypothalamus and the higher centers of the brain that are going to send a signal to the respiratory center and send a signal actually to the medulla and give the order from the hypothalamus to stop breathing and to hold your breath okay so you're going to do it you're going to stop and up you're going to stop breathing but obviously when you do that after a couple of seconds and you're going to start to accumulate carbon dioxide, you're going to start to decrease your oxygenation.
So there are physiological mechanisms that are going to start to change. Your partial pressure of gas are going to start to change, for example the oxygen might start to drop a little bit, your carbon dioxide might start to increase and then your pH is going to start to also change a little bit. So that's the idea of evaluation. The medulla It's going to evaluate the signal. In that case, it's going to evaluate the signal coming from the hypothalamus that is telling me that I need to hold my breath.
It's also going to evaluate the signals coming from the carbon dioxide, coming from actually the peripheral chemoreceptors or the central chemoreceptors, coming from other receptors in our body. The goal of the medulla is then to prioritize the signal. Now that I know what the signals are, I know that the signal for the hypothalamus and the signal for other receptors in my body is telling me that there is something going on. I need to prioritize which one is the most important and which one do I need to obey actually for my respiration.
And after a minute or two, obviously the most important signal is actually coming from the pH and the carbon dioxide. At that point, I need to breathe because I need to maintain my pH. I need to maintain the carbon dioxide pressure. I cannot have a decrease of pH. For example, this is one of the priorities of any type of physiological mechanism is to maintain the pH. So the medulla received the information and then at one point it's going to be clever enough.
If you want to understand that, okay, the hypothalamus is important because it's my brain. And again, I'm receiving order from the hypothalamus and I usually answer those orders. But at one point, at a certain threshold of change for my pH or my carbon dioxide, I need to prioritize that and I need to stop answering, I need to stop answering the hypothalamus and I need to start answering the pH and I stop holding my breath and I start to breathe.
And then you feel the contraction of the diaphragm, you feel the spasms of the diaphragm and so on because it's the order from the medulla that says, okay, now you need to breathe and you have this change of pH. So really, you need to keep in mind that the medulla is actually doing the job. The medulla is really the center compared to the pons that we'll see just after. The medulla is the one that has the capacity to start to breathe or to stop to breathe.
Really to have this big, if you want, impact on the respiratory system. The voluntary, the involuntary pattern is going to be organized by the medulla. So you see here. On the medulla, you have the respiratory centers that are actually one cluster of cells, one nucleus of cells that are in this particular location.
And there are others, obviously, as you can see here, that are also part of the medulla. But for now, we don't need to talk about any of those, the cardiovascular or any other ones. Okay, so depending on the metabolic needs and also the voluntary. needs, it will send all signals to the respiratory muscles.
So, we've seen the medulla briefly, let's see also the pons briefly. The pons, so p-o-n-s, the pons in Latin means bridge. If you speak a Latin language, like French or Spanish, then you know that in Spanish it's puente. In French, it's pont, also P-O-N-T, so it means bridge.
And that's exactly what it is. The pont is the bridge between the higher centers of the brain and the medulla. That's why it's on top of the medulla. And you also know that anatomically, when things are on top of each other, it means that usually the one that is on top is responsible for the control of what's at the bottom.
So, well... we'll see right after but the role of the pons is actually to control the medulla so we'll we'll see that right after there are two most important centers in the pons there are actually also two important centers for the medulla that i forgot to mention before but i will do that after there are two most important centers for the pons one is called the pneumotaxic center and the other one is called the apneustic center. You have them two, the two here and they are represented here. They are called bilateral centers on your pons. Those two will be very important and we're going to see with the graph just after what's the role of those two centers, the pneumotaxic center and the apneustic center.
For the nerves and the sensory motor, that's okay, you don't need to read the numbers. Okay, what's the role of the pons? We've seen the role of the medulla right before, and I said it's to evaluate and prioritize the signal.
Now, for the pons, we usually say it's to modify and fine-tune the signal or fine-tune the breathing pattern. So what does it mean to modify and fine-tune? It's actually not the pons itself that will be able to start to increase the ventilation.
If you... if you start to run, so you go from a quiet breathing to a really intense breathing, so you start to run and you need to increase the ventilation a lot. It's actually the medulla is going to send a signal to say, okay, now start to increase the ventilation.
But what is going to be able to match this ventilation with the metabolic demands and really to fine tune this ventilation is actually the pulse. So it's not going to be able to completely increase or decrease the ventilation, but it's basically going to fine-tune this ventilation. If you remember here, if I'm drawing here on the graph, remember the slides, of the different phase of the ventilation, 1, 2 and 3. Then the metadata could be responsible for what you see here, which is the ventilation and the, depending on the...
the time or depending on the intensity of the exercise. But the PONS is actually going to fine-tune this ventilation each time there is a change of the metabolic demand going to up and down to really fine-tune the ventilation. So it's going to modify and fine-tune the breathing pattern by playing on volume and frequency.
Okay, sounds good. Pneumatic center. dorsal and ventral. So that's the two I forgot to mention before. For the medulla, you see on this side on the right, on the graph, the ventral respiratory group and the dorsal respiratory groups are those two centers important in the medulla that will be able to control the ventilation.
Okay, so here's a graph that I want to spend a little bit of time on it because it's important and I really need you to understand this graph and the big principle of this graph. So let's start. You see here the pons and the medulla. So it's basically the respiratory centers.
So it's a semantic representation of the relationship between the pons and the medulla in also... the context of the control of breathing, especially during exercise. So we're going to start from the top, we're going to start from the pons, and then we're going to go down and talk about the medulla. So I told you before, for the pons, there are two centers, the pneumotaxic centers, the pneumotaxic center here, and the apneastic center here.
The role, we're going to start actually, I want to start with the apneastic center. The role of the apneistic center, like the name, apnea is an aspiration without an expiration. An apnea is you inspire and then you stop expiring and you cannot expire.
That's an apnea when you say you're going to do an apnea. So the role of the apneistic center is here, as you can see, plus, meaning that the plus is going to stimulate the aspiratory centers and at the medulla level. So it's going to activate, it's going to send signal to the aspiratory centers and in return this aspiratory center here is going to activate your inspiratory muscle, the diaphragm being the most important.
Constant, so here I'm talking about the constant aspect is that whatever is happening There is always a stimulation coming from the apneastic center to the inspiratory centers. That's why, for example, you can breathe and you can inspire when you sleep. You don't need to think about the inspiration and you're going to constantly have a signal coming from the apneastic center to stimulate the inspiratory centers and to inspire. So that's one of the most important commands actually of the controller ventilation.
It's coming from the apneistic center to control the inspiratory center and to start an active contraction of the muscle to induce the inspiratory process. Then whatever is going to happen around this axis, of apneistic and inspiratory centers is actually going to control this inspiration. And the first thing that controls this inspiration is the pneumotaxic center. The pneumotaxic center will actually send an inhibitory signal. You see the minus here.
You see an inhibitory signal with the minus that stop, it means that it stops the inspiratory centers. It sends signals to stop the inspiratory centers. And this is a constant signal.
So constantly, the pneumothoracic center will stop the inspiratory center. So when you put that together, between the apneustic center and the pneumothoracic center, you have a constant activation coming from the apneustic center and a constant inhibition coming from the pneumothoracic center. And that gives you actually what's happening during quiet breathing.
Because during quiet breathing, Remember what I said on the first slide, is you need an active inspiration, which is the case. You have a plus, you have a constant stimulation coming from the apneotic center. And then you have a passive expiration, you don't need energy.
It's because you have this inhibition coming from the pneumothoraxic center. And that gives you a cycle of inspiration, expiration, inspiration, expiration. And when...
Okay, so that's how those centers are able to communicate to each other and control the restoration. One thing that I want to really develop also again here is that, that's a little bit more of a difficult understanding, is that to be able to expire, you actually need to stop inspiring. You need to stop the inspiration.
And that's what's happening here in green with this link between the two. So indirectly, when on top here, the pneumotaxic center stops the inspiratory center, there is what we call a tonic activity of the expiratory center. So what's a tonic activity? Is that when you... when you send an inhibitory signal, you actually activate this and you are going to help the respiratory muscles.
There's always a link with the respiratory muscles. So there's this indirect role of the pneumotaxic center that inhibits constantly the respiratory center. And by inhibiting the respiratory centers, they are able to actually activate the expiratory centers. and release, if you want, this tonic activity that is always happening and then allows for the expiratory muscle and especially the elastic recall of the lungs to happen at rest.
So now this is what's happening at rest. What's happening during the exercise? Actually, what's happening during the exercise is a control of this by here you see on top the situational inhibition of the pneumothaxic center to the apneustic center.
And that's it. It's actually a very clever system in that sense, is that to be able to increase the ventilation coming from a resting to an exercise, what do you need to do is actually to stop more often the inspiration. If you stop the inspiration earlier than during the quiet breathing, you actually start an expiration earlier, and what you do is you start to increase the frequency.
So you stop the inspiration earlier, you start the expiration earlier, and then you start to increase the frequency. So it's a little bit not really intuitive to understand that this way, but to increase the ventilation, you actually need to stop. That's why there is a negative aspect here, a negative signal coming from the pneumotaxic center. You need to stop the aspiration.
And then stopping the aspiration here will activate even more because I told you before that the expiratory center is associated with This tonic activity of the expiratory center is going to activate this expiratory center even more and activate the expiratory muscle this time and all of the other muscles, the accessory muscles, the abs, the intercostal muscles and so on. So I wanted to really introduce you to this graph. It's a little confusing now. To introduce to this graph talking about inspiratory center and expiratory centers. But it is actually here you see the definition.
The inspiratory center is actually the dorsal respiratory group of the medulla. And the expiratory center is actually the ventral respiratory group. So you know dorsal means the back, so the posterior respiratory group.
And the ventral means the belly, it means the front of the medulla. So in that sense, it's also pretty well organized anatomically, because the back will be responsible for the aspiration, and the front will be responsible for the expirations. And that makes sense also with the spinal cord.
This graph here is a little bit crowded, but it's actually the same thing as I said before. You can recognize here the pons and the medulla, and the relationship between the two. You don't see here the relationship, but I explained that before. Just what you see here is the feedbacks that are going to be able to control all of that. So this graph that I showed you before is actually the main respiratory centers without the feedbacks, without understanding what's going on in the rest of the body.
The change of pH, the change of partial pressure of gas, the change of temperature and all of this. This is just the main respiratory centers that control the respiration. Now, when you put all of this together, you can understand how difficult and how complex the system is. The chemoreceptors here being the most important. So we said the central chemoreceptors and the peripheral chemoreceptors will act and will send signals directly to the respiratory centers in the medulla.
For example, if you follow the... arrow here. The mechanoreceptors that are responsible for proprioception and the one that you can find in your muscle can do both inspiratory and expiratory muscle and expiratory centers. And so I'm not going to ask you to memorize those links between the different feedbacks and the centers, but it's just for you to have a big picture, right? If you keep this particular graph in mind and especially if you're able to explain this graph to others so you will be all set to really understand the the big picture of the control motivation and then we'll describe some some of those receptors but you'll be uh you'll be good um on that part so i would like really for you to uh to understand that okay Okay, so I'm going to stop that here because it's a good introduction, I think, from this first part of the controller ventilation and controller breathing.
I'll do another lecture later on to just talk about the central chemoceptors, the ones that are sensitive to pH and carbon dioxide. And we'll do another lecture on the peripheral chemoceptors, and I'll give you some examples, especially during exercise after that. So...
Stay tuned for the next lecture.