Transcribed by Amy Maya Organ Systems Mechanics of Breathing by Evgeny Pavlov ** I apologize if the grammar seems off, but

t I 1 Intro slide

3.27.2014

The second lecture is mechanics of breathing. First lecture we talked very general terms and now well talk in more details in certain aspects of the respiratory system. It is all pretty straight forward but somewhat more in depth and tricky.

2 Mechanics of gas exchange between lungs and environment Just to remind you, its all about change of the volume of the lungs in a dynamic way so you contract lungs, push air out, and let air in. It is a relationship between the change of volume of the lungs and change of pressure inside lungs, this space here. This is guided by the Ideal Gas Law. The central goal of this lecture is to look at forces that provide change of the lungs. How the lungs are able to change volume and change pressure with breathing, and what forces resist, how it goes smaller and bigger. 3 Objective This is our objective to understand the forces that move lungs and resistances they must overcome. For air to go into the lungs it needs to go into the airways which has resistance so we need to know how this works. To understand this we will talk about muscles of respiration and how it is related to the function of the lungs and then about the elastic properties of the lungs and chest wall. I will introduce the concept of compliance of the lungs, the physical and elastic properties of the whole system. Another point is the surface tension of the alveoli, the small balls inside the lungs and how they are covered in surfactant. I will talk about the composition and role of surfactant and how it is critical for lung function in terms of elasticity. And then we talk about airway conductance and resistance, seeing how air flows through the lungs. Then ill talk about work of breathing so how much energy you need to pump air in and out of the lungs. 4- Ventilatory flow It is all about the pressure difference, we have 2 types of pressure, we have alveolar pressure, which is inside the lungs and we have atmospheric pressure, which is outside. And atmospheric is fixed. Change in alveoli pressure above or below atmospheric defines airflow in and out of the lungs. There are 2 types, there is inspiration when you move air in, expand the lungs caused by contraction of the muscles, this is important because the diaphragm muscle contracts. It is guided by the Phrenic nerve resulting in the expansion of the lungs. Inspiration also helped by external intercostal in the ribcage. You need muscles to contract for lungs to expand. Expiration is passive, it is due to elastic recoil of the lungs so under normal

Transcribed by Amy Maya

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conditions the lungs go back to normal unless there are high ventilation rates where abdominal and internal intercostal muscles kick in to help push air stronger out of the lungs. 5- Respiratory muscles Those are the lungs schematically represented. Two things we have the active process of the diaphragm, which contracts and goes down which increases the volume. This is another view so this would be related to inspiration since expiration is passive unless it uses abdominal muscles to cause diaphragm to go up and strengthen the process of expiration. 6- Mechanics of breathing The muscle here so we have the diaphragm, abdominal muscles and we have intercostal muscles, external and internal in between the ribs. During inspiration we have elevated ribcage and the diaphragm moves down to increase the volume. 7- Lung-structure-histology Now looking at lung structure and histology and what is important is the general organization of the lungs and chest wall how they are all working together. The lung is in the thoracic cavity and you have two walls surround the lungs. Visceral pleura surrounds lungs and parietal pleura surround thoracic cavity. You have a few microns thick space called the interpleural space. It is a sealed tight space and filled with pleural fluid and this is important. You would have lungs surrounded by 2 layers and their elastic properties define the forces and elastic properties of the lungs. 8- Lung-structure-histology So the analogy would be good between two pieces of glass if you have these 2 layers move and slide against each other but are anchored to each other. They do not separate they are tightly sealed. This defines that you have 2 layers of the lungs but as the lungs grow (in volume) they slide against each other. They are very tightly connected in terms of elastic properties and this is important as 2 tissues working together. 9- Model structure of the lungs (Apologies when he was explaining it, he was all over the place but the diagram makes it easier to understand) This is cartooned here, we are not talking about anatomy but more of physics, the forces. This is the model of the lung essential for todays section. We have 2 layers, lung wall and chest wall working together and defined in mechanic properties of the lungs. We have two pressures, the barometric (PB) and alveolar pressure (PA). We have the barometric, which is outside, and alveolar pressure, which is inside. We have transpleural pressure. And the whole difference between 2 pressures is the pressure of the respiratory system (Prs),

Transcribed by Amy Maya

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between alveolar and barometric here. Since there are 2 layers, you have like 2 things going on. So there is one pressure between alveoli and interpleural (Ppl) and this is referred to as pressure of the lungs (PL) and the other is pressure of the chest wall (PW) which is intrapleural and barometric. They work against each other and I will explain how this happens. But the pressure of the lungs is actually related to the volume of the lung. 10-Compliance The first very important parameter, which will be used to describe flexibility and expandability of the lungs, it is called compliance and this is very important. This is defined as a relationship between change of volume of the lungs divided by change in the pressure, how much pressure you need to apply to change to a certain volume. As an introduction it is intuitively clear I would imagine, if you have some ball you would try to inflate going from this to that so you apply more or less pressure. This compliance here is that property of the lungs, to apply and to change, very critical and important. 11- Elastic properties of the lungs This is how it is measured. This is an important slide in understanding the elastic properties of the lungs. So we want to see how lung pressure is related to lung volume. Here you have a very simple experiment with just the lung, no chest wall. So what you have is a lung, which has barometric pressure inside equilibrated with this chamber here. And on the other side we have also barometric pressure to start with and this would be zero because this is pressure on the lungs so essentially the difference between alveolar and intrapleural pressure. But in this model you would have zero because the difference is atmospheric here, atmospheric there. But if you start pumping air out, you create less pressure inside and lungs will expand because they try to equilibrate with the environment. They try to expand so pressure inside will start dropping and the lungs start to get bigger until they stop at a certain volume. So volume of the lungs has relation to pressure. The expandability is relayed to the elastic properties of the lungs so you could have a similar experiment in blowing up a balloon and it expands and it kind of equilibrates at certain levels. So this is a similar experiment except you kind of blow up the balloon by pumping air out. But it kind of defines this curve, which determines the compliance of the lung, the elastic properties of the lung and there are a couple of important things here. It is not linear, so it makes it harder and harder to expand the lung and if you stretch them too much you have resistance in the lung wall as you get bigger and bigger. So you cannot go beyond a certain points in terms of increasing pressure 12- Elastic properties of the lungs What defines the elastic properties of the lungs? There are 3 key things. The first 2 are very simple you have this analogy of rubber, this is how you stretch the lungs. It is like collagen and some fibers, it has some elastic properties so you can stretch it and it recoils back. These are what the walls are built of. But then you have surface

Transcribed by Amy Maya

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tension and this is really not trivial and we will talk about it for the next few slides. This is very important. 13-Compliance-disease But first I want to demonstrate what would happen with emphysema related to compliance. This is loss of alveoli, loss of lung tissue. You have alveoli walls, which are largely destroyed and gigantic change of volume with less surface tension. The volume can increase really high without too much pressure applied which leads to increased compliance so volume changes much easier when you have much less tissue. The opposite is true for fibrosis when you have too much tissue built up on the lung walls so a lot of fibers making it more stuff and decrease in compliance because need to apply much more pressure to expand lungs enough. But here you try to expand and they will not comply so the stiffness goes up. 14-Surface tension This is very important in terms of physics it is easy to understand surface tension. By definition surface tension is the force at the liquid air interface that holds liquid together. The pressure caused by surface tension is directly proportional to the tension itself and inversely proportional to the radius of the sphere 15-Law of LaPlace describes surface tension forces Here are the alveoli and the Law of LaPlace so you would have surface tension like here so you would have air and then you have interface and there is some leakage covering the membrane and then you have all this blood covering the tissue. The surface area of the alveoli is covered by leakage creating surface tension. So you have air inside the lungs and the air holds them open and surface tension tries to make them collapse. LaPlace Law says its inversely proportional to the radius of the spheres. The alveoli are slightly different in size, one bigger one smaller. The bigger alveoli have smaller surface tension pressure. What happens since air is the same everywhere but the surface tension pressure is different, what happens is this smaller ball will collapse because the pressure is higher and it will collapse. This does not happen in healthy lungs because of surfactant but sometimes in pathology it does happen like in newborn babies who dont have this feature. It used to be a clinical problem before it was figured out. This is not hypothetical, but it occurs in real life. 16-Surfactant It is not happening because of surfactant. The surface of alveoli is covered by surfactant, which reduces surface tension on alveoli. It is synthesized by alveolar type 2 cells and primarily by phospholipids, more specifically DPPC, you dont need to know its exact chemical composition. It also contains some collagen like glycoproteins. Surfactant also helps to dynamically change surface tension and this experiment here illustrates this point (next slide).

Transcribed by Amy Maya

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17- Surface tension measurements Here is what is so unique about surfactant. In this experiment you would have some metal like platinum strip dipped into liquid that you want to measure surface tension. Due to surface tension if you try to pull it out it tries holding back in the liquid. With the force you use to try to pull it out, it will give you the amount of surface tension. You measure it for different surface areas so you have this barrier, which changes the surface area for the experimental conditions so at like 100 you have this big box, and you move the barrier and make it smaller and measure the surface tension. If you use just water and move the barrier nothing change, the surface tension stays the same. If you use detergent on the surface, the surface tension becomes less but it still has the same surface tension regardless of how big the area is. (This next sentence is horrible but I listened to it several times and this is literally what he said) But if you use surfactant, the surfactant surface tension it like really changes dramatically with the area which is used and in terms of biochemistry (we will not talk specifics in biochemistry processes) you would have all these lipids lining out the surface and they get more or less squished and this dynamically changes the surface tension in such a way that increases as you increase the area of the film and it drops if you reduce the area of the film. 18-Effect of Surfactant of lung compliance This defines the elastic properties (compliance) of the actual lungs comparing to lungs without surfactant (saline). You could see how dramatically different the properties would be of the lungs, it would dramatically changes compliance and this is important in the role of surfactant. 19-Law of LaPlace in the context of alveoli structure What is more important is that it changes the surface tension dynamically. This is critical for the alveoli of different sizes. As you have seen, the bigger the area, the stronger the surface tension. Overall it results in the balanced pressure between these two and that is why alveoli dont really collapse in healthy individuals. In premature newborn babies, this is an illustration of the importance of surfactant. Surfactant gets produced at the later stages of development so in premature newborn they will not have surfactant so alveoli are open for breathing but they do not have surfactant so the alveoli have a problem of collapsing. For newborn babies problem they dont have much surfactant so they can be administered artificial surfactant to overcome this.

Transcribed by Amy Maya 20-Distribution of ventilation

3.27.2014

This is the intrapleural pressure curve and compliance of the lungs, the relationship between intrapleural pressure and the distribution of ventilation. You can see in upright standing lungs, due to the gravity it will be different levels so it will be minus 10 on top and slightly lower on the bottom. So what you can see here it the alveoli located at different areas of the lungs are located at different areas of the curve and if you apply the same amount of pressure the volume change will be much higher in the bottom of the lung compared to the top. This is a key mechanism that shows the original difference in the lung ventilation.

21- What determines lung volume? But what about the total lung volume? We have the first surface which is the surface surrounding the lungs, the lung wall. But the actual wall of the lungs is a combination of elastic and tension properties of the chest wall which essentially attach to the lungs and this can be described by the relaxation pressure volume curve. (Below is the paragraph I typed up from attending the other lecture, the one that wasnt recorded, and it explains it a little better... slightly.) (This is I just mentioned we have all this elastic properties of the lungs but it is actually the combination of 2. So the lung volume is determined by elastic properties of lungs AND the chest wall so if you recall there are 2 parts to the equation. Inside are the lungs and outside is the chest wall, together combined and described as relaxation pressure volume curve) 22-Relaxation pressure-volume curve (He says here a lot as he points to the screen We have 2 components here, one is the lungs, the other is the wall. RS stands for respiratory system, this L stands for lung, W is for the chest wall. These 2 types of pressures work together and the muscles need to overcome to expand the lungs. TLC is total lung capacity, FRC is functional residual capacity and RV is residual volume. This is maximally contracted, most expanded here and here is the normal so this represents 3 volumes. So in terms of them working together, if you want to expand lung as much as possible you need to overcome these two resistances so the chest wall and lung both need to press the lungs back to normal conditions so this is the sum of these 2, that is what you need to overcome, that is the force you would need to expand lungs maximally. And this would be your normal resting breathing so you have 2 forces coming together so pretty much they balance each other, the wall and the lungs, and this is the place where it is easiest for muscles to manipulate. So here you try to maximally expire air and here the opposite force tries. What happens here is the lungs are not relevant anymore because they cannot go below

Transcribed by Amy Maya

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certain size so they cannot push it out but the chest wall tries to expand so its like opposite directions and muscles need to overcome this expanding pressure which happens in forced expiration. The overall conclusion for this curve is defined by the pressure volume curve for the lungs themselves and for the chest wall. 23- Lower airways So now we are going to the second part. The first part was all static properties of the lungs, we didnt talk about airflow, we talked about pressure you need to apply so it was all static. So this is about the flow of the air and what laws define this so lets looks at lower airways, which are highly branched. So we have a conducting system, which is essentially many tubes from trachea, branched to bronchi to alveoli, we have this airway structure to primary bronchi then smaller bronchi. There are 23 divisions going down to alveoli and conduction system is up to roughly 11th division so there is no air exchange happening until the exchange system, which is bronchioles and alveoli with thinner walls allowing exchange. So the individual diameter of each branch you get smaller and smaller, but the total cross sectional area gets much larger with every division. 24-Cellular structure of airways For our purposes we dont need to know much about the anatomy but to know the difference between conduction system and exchange system so we have conduction system which is covered with cilia cells covered with mucous so it doesn't exchange the gas but the property of this is to transfer air from the outside of alveoli and back. This is essentially what air needs to overcome.

25-Dynamic mechanics of the lungs The dynamic mechanics of the lungs is essentially defined by the resistance and you will need to know this equation. The resistance is linked to the difference in the pressure between pressure is on the alveoli on the outside and the rate of the airflow. You have two pressures on the different sides and the flow rate is defined by resistance of the tubes themselves, of the airway system. Here I will give an example of the distribution of this resistance so this will be airway regeneration so the number of divisions so it will be like 10 corresponds to this level, 5 is this one here. This is not linear and this illustrates how resistance drops with the branched number and this drop is due to the fact that although tubes become smaller, the number of tubes becomes bigger so cross sectional area gets big and it is easier for air to flow closer to alveoli. 26-Airway resistance of the lungs There are 2 types of flow of the air in the lungs from the outside into alveoli. Laminar which is smooth parallel flow of the air, and turbulent which is very

Transcribed by Amy Maya

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irregular flow. In the airway the flow is a combination of two. Sometimes laminar and sometimes turbulent. 27-Airway resistance of the lungs Dont worry about these equations for laminar and turbulent flow because it is kind of extra but just be aware that they are proportional to the rate of the air flow and one is linear and one is squared. In the lower airways flow it mostly laminar and in upper airways it is mostly turbulent, and in between it is mixed. You can kind of ignore this slide it is not very important. 28-Airway resistance of the lungs What is much more important is the relationship between airway resistance and the cross sectional area of the airway system which is very important in disease. You need to know relationship between resistance and the size of the tube. Dont worry about the rest of this equation, (just know it is proportional). Resistance is proportional to the power of 4 of the radius of the tube and this is true for the airway system as well so it drops dramatically with the radius increase and it increases dramatically with the radius decrease. I make a big deal of this because this is key for asthma, which is dangerous. Even if the airway diameter changes twice, the resistance can change 16 times. So please remember this power of 4. 29-Airway resistance of the lungs Now it is easier to understand why resistance dropped dramatically if you look at each step, not as a whole. Because this R gets smaller and smaller but here we are talking about the sum of all cross sections and they become bigger and bigger and you get this drop to almost zero resistance as you increase the number of divisions. 30-Key dynamic lung parameters during normal breathing Now we will just summarize the dynamic properties of the lungs during breathing, inspiration and expiration. This brings together the dynamics and static properties of the lungs. Lets look at inspiration vs. expiration. First is volume change which increase during inspiration and this is directly related to the flow rate. If you take first derivative of that is flow rate, which is very simple. We have volume change, and as much as we change that translates to the flow rate. This is also true for other pressures, so if you change volume, you change alveoli pressure. I guess ill just describe it here so what you need to overcome by applying intrapleural pressure. If this is all you needed you would have just this dashed line a very linear relationship. So you change the volume and thats it. In addition you also need to overcome the resistance of the airway system, need to overcome this extra pressure to overcome the resistance so air can flow in and create this phenomenon. In the ideal case, if there was no resistance you would need to change intrapleural pressure just to expand the lungs and this is the dashed line. So youll be just applying enough pressure just to expand the lung to a certain volume so you're just working against this elastic property of the lung. This is the dashed line. But in a real situation you

Transcribed by Amy Maya

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need to expand the lungs, so this is the change of the pressure while also overcoming resistance, you need to have some extra push to have this meaningful change in the pressure. The size of this shaded area would describe how much extra pressure you need to apply to overcome the resistance of the airway tubes to get air into the lungs. 31- Flow volume curve This is the flow volume curve and it is not that complicated so one important concept is based on the expiratory flow in the lungs is effort independent. You have the capacity of the lungs and this here is the vital capacity. You have maximal expiration and maximal inspiration all the way around, so this is the smallest, this is the biggest. In the middle is the tidal volume so if nothing serious is happening you have this flow rate for inspiration and expiration, a kind of nice small circle. But what happens here, the person who was studied inhaled and exhaled with different intensity, you could do deep slow breath or fast maximal effort breath and this is half effort. Inspiration is intuitively clear so the more effort you make the more intense the curve is. So the same change of volume but much faster flow for inspiration. For expiration it is really different, what happens is the flow in the lungs becomes effort independent so no matter how hard you try to expire, the rate will be the same. Whether its half, or normal or maximal effort, it is all the same flow rate.

32- Dynamic compression of the airways This is explained by a very important concept, the dynamic compression of the airways. You would have different values like before inspiration you would have all zero here, you would have some intrapleural pressure, and you kind of balance pressure of the capillaries. Then during inspiration you create some more negative pressure so the lung expands and air flows. Then during forced expiration, you would try to apply a lot of pressure on alveoli and try to squeeze them and if you press them really hard, create really hard pressure inside alveoli, and it ends up with big pressure buildup inside and zero outside which is barometric. But there is some gradient of pressure between really high 38 and zero outside, and, at some point, so yes it is a gradient, so there is a drop of pressure but in terms of intrapleural pressure it is all the same like not only in alveoli but in the airway system so if the pressure drop becomes big enough you have compression of the airways so they will be squished by high difference in pressure because it dropped in the airway but it is still high in the pleural pressure. The end result is it gets squished and the more pressure you try to apply, the more you try to push air out, the more it will squish so overall it results in effort independent process due to this contraction so the more you try, the more they compress and it will be essentially effort independent. The more force applied, the sooner they will collapse.

Transcribed by Amy Maya 33-Work of breathing

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I want to talk about this concept of work of breathing both in normal lungs and in lungs with increased airways resistance. What you can see is the work of breathing is the pressure multiplied by volume change. If you have ideal conditions (NOT normal lungs) with no resistance you go from A to C. Inspiration will produce some work so it will go A B C to breathe in. You then have recoil and it will go C B A (expiration) so combined there will be no work applied. But since you do have resistance you would inspire air, and the work would go to expand the lungs against the elastic properties, plus it will need work to overcome resistance of the airways. When exhaling, some work is needed to overcoming the airway resistance so overall this A E C F will be the normal breathing. In asthma, you would have increased airway resistance and you have to work against a much harder resistance. It is much harder to go through the cycle A E C D F and back to A. It is even hard to expire the air so it is so important to keep airways clear. 34-Summary So to summarize key points: Inspiration is an active process and expiration is passive recoil due to elastic properties of the lungs. The diaphragm is the main muscle of respiration involved in active process of inspiration. Compliance is the key component in elasticity of the lung. Surfactant is necessary to prevent alveoli collapse between different sizes by evening out the pressure between them, by reducing surface tension. Airflow is a mixture of laminar and turbulent flow, which is different in different areas of the lungs. Airway resistance drops significantly in the respiratory zone so when you approach areas with much larger cross sectional area. Expiratory flow is effort independent, which is explained by the phenomenon of dynamic compression. And work of breathing dramatically increases with the increase in airway resistance. This is the first two lectures and tomorrow we will have the other 2 about ventilation and profusion relationships and then neural control of breathing. That is it for the day, yea, thanks. (Awkward clapping)