now we're going to turn our attention to the respiratory system and in particular we're going to begin with what occurs within the lungs the gas exchange between the air that you inspire and the blood that flows through the lungs now the respiratory system [Music] does exist so that we can bring oxygen into the blood and offload co2 there's also the ability to control ph we'll get into that in a little bit why do we need to do this well because all of the cells of the body require oxygen to undergo aerobic metabolism which provides a very high yield of atp in the cells for each molecule of glucose or fatty acid that makes it inside the cell and a byproduct is co2 okay so we have the lungs and all the vascularization within the lungs because of that because the cells need oxygen so the first question that we're going to address is how can gas exchange be maximized so we're going to consider the physical principles of exchange we're going to consider the role that blood chemistry plays in this and in particular the solubility of oxygen in the blood and then finally the transport of carbon dioxide so on each of these subjects we're going to pose the question how do we get the most how do we get the best exchange and you can think of this in the context of activity or even intense exercise that the respiratory system and the circulatory system in its delivery of oxygen provide limiting factors to activity um if you have insufficient ventilation in the lungs or insufficient circulation then you will feel fatigued and you cannot meet the aerobic demands of cells especially exercising cells the skeletal muscles all right so let's start with the physical principles and we're going to consider the physics of gases first and what we've got here is a beaker and this is going to provide us with a simplified greatly simplified model for what occurs within the lungs so you breathe in that ventilates very small containers called alveoli we'll talk about those later that hold the air in close proximity to capillaries that carry the blood through the lungs so in this model the the gas mixture above this interface which is just a volume of water um serves as a model for the air inside of the inside of the lungs compared to a liquid which is our model initially for the blood that flows through the capillaries so the air pressure itself even even at elevation air pressure which is generated by the collisions of gas molecules against surfaces after all these gas molecules have mass and they move around with random thermal motion but that motion sometimes causes them to collide with surfaces like the wall of this beaker or the surface of the water and they'll either bounce off say a solid surface and impart some momentum to that surface that's what generates pressure or sometimes they'll actually penetrate a liquid surface so you could say that air pressure is driving in this case oxygen so we've labeled the molecules here that correspond to oxygen the most popular gas in the atmosphere is nitrogen so you can imagine most of these gray dots or nitrogen molecules so we have some oxygen penetrating the surface and diffusing into solution now here's where the ideal gas law comes into play the ideal gas law is a model of the relationship between pressure and other aspects of a gas that's in a container so we have the volume of the gas within the container you have the number of molecules in terms of moles of that gas that's within the container then there's a couple of constants so you have the gas constant and then temperature which can change but in the body it stays pretty consistent so what the ideal gas law lets us do is consider what factors influence the pressure since we've established on the left that pressure is driving the oxygen into solution if we can change the pressure of the gas mixture above the interface then we should be able to manipulate how much oxygen we drive into solution so if we take the ideal gas law and rearrange its terms we can see that we can come up with an equation for pressure and we can see that if we want to maximize the pressure again how to get the most exchange then we can elevate that pressure of the gas by in one sense reducing the volume of the gas mixture above the interface so we do this virtually here by adding a plunger to our system and just imagine comparing the beaker on the left which is open to one where we have a closed volume and we're going to make that volume smaller so that's going to serve to elevate the pressure which is going to drive more oxygen into solution and give us a higher concentration of oxygen molecules now we can go back to the initial form of the ideal gas law to see that the product of pressure times volume is equal to all the other stuff in the equation so what is that well it's the number of gas molecules some gas constant something that's not going to change and the temperature which for our current purposes doesn't change either so in other words the product of pressure and volume is fixed provided all the other stuff stays the same and that relationship is important when we think about what occurs within the lungs and it was initially formulated by boil and so we have this left hand side of the ideal gas law pv included in what's called boyle's law so boyle's law says that basically pv is going to stay the same so if we look at the pv on the left we could just imagine there's a sort of virtual ceiling to this volume because that's where the plunger began before it moved downwards so that volume times the pressure is going to be equal to the same product on the right hand side and since we have reduced the volume that means we've increased the pressure okay so this is formalizing something i think makes intuitive sense which is we've got a fixed number of gas molecules each gas molecule contributes to pressure and when you reduce the amount of space that those little masses have to bounce around then you're going to increase the frequency that they encounter those surfaces and that's going to impart more momentum which is going to be reflected in the pressure okay so we're making basically a tighter space for these little bouncing uh balls of these little gas molecules and if you reduce the amount of space that they have to move around you're going to elevate the pressure okay another um trick for enhancing exchange would be to manipulate something else in the equation and in particular if we change the number of gas molecules so the moles of gas and rather than changing the total number which would affect things but um quite often you know the atmospheric pressure is beyond our physiological control it's just dependent on our current elevation so we're um if you're at sea level then that's one atmosphere of pressure that you can't really do much about but just imagine that instead of changing the total number what if you were to swap out some of those nitrogen molecules for oxygen molecules again not really physiologically possible but we're just playing a thought experiment here and um and so we do that on the right hand side so even though the total pressure would be the same in both of these beakers because we've swapped out or we've enhanced the proportion of those gas molecules that are oxygen then you would expect a higher concentration on the right beaker than on the left beaker because of that swapping of the molecules and this illustrates something known as a partial pressure which is formalized by dalton's law so dalton's law is it's pretty simple so it's basically that the idea is that the total pressure air pressure this is is generated by all of the gas molecules bumping into things and so the proportion that is due to any particular kind of gas like oxygen is just quite simply the proportion in numbers of the gas mixture that is composed of that type of gas so the partial pressure is essentially the proportion of pressure so that's either pascals or millimeters of mercury that is generated by one type of gas so here we have the partial pressure for o2 that's oxygen is the product of the total pressure so that would be like one atmosphere at sea level times the percent of oxygen that's in the air so on earth that's 21 percent now you can calculate a partial pressure for any gas it could be nitrogen it could be carbon dioxide um and we can apply dalton's law just take the total pressure multiply it by the proportion uh of the total of the gas mixture that is composed of that particular type of gas so we can do that calculation so in the air we have for oxygen they're 21 carbon dioxide is tiny okay we have .033 percent of the air that we breathe is composed of carbon dioxide now if we multiply those proportions into the atmospheric pressure at sea level then we can find the partial pressures of the two and so because of that really high percentage and we're multiplying those percentages by the same number then not surprisingly you get a really big number for oxygen you would say that the partial pressure for oxygen shown in red favors diffusion into the blood because you can think of the partial pressure as being a driving force okay what we saw in the in the last example of the beakers was that in those two cases the total pressure was the same but because on the beaker on the right we had a higher proportion of o2 that meant that the beaker on the right had a higher partial pressure than the one on the left so it's really partial pressure that matters as a driving force for diffusing a particular gas into solution so the partial pressure for o2 is much much higher than co2 and it's really the partial pressure difference between what's in the air and what's in solution so given that carbon dioxide is a very small offers a very small partial pressure that's going to favor the diffusion of co2 leaving the blood in the lungs whereas that very high partial pressure for o2 provides a driving force for diffusion into the blood so we can say that the gas composition of air favors the exchange that we want we want as much oxygen into the blood as possible and as much co2 to leave now that brings us to the other side of this equation okay so air favors what we want that is this exchange of o2 and co2 but on the receiving end we've got a problem and that brings us to blood chemistry so let's consider an example so this is unrealistic as i just laid out in that the partial pressures for o2 and co2 are equivalent and we're doing this unrealistic scenario in order to illustrate what happens on the receiving end that is the solubility of these two gases so we're offering the same driving force to provide a controlled virtual experiment so if we have both 100 millimeters of mercury for co2 and o2 and we measure the concentration of these gases in solution then what we find is that the concentration for o2 is something on the order of 0.15 millimolar per liter okay that number by itself doesn't really mean very much but if we compare it to co2 we can see that many more co2 molecules dissolve into solution in fact that difference is 20 fold carbon dioxide's 20 times more soluble in water than oxygen is okay that's a problem if the goal is to bring oxygen into the system into the liquid and we want to get rid of co2 we can see that water provides a challenge because water is really greedy it wants to hold on to co2 and and it doesn't really take on much carbon dioxide now we might ask the question is water a reasonable model for blood blood's got proteins you've got red blood cells all kinds of stuff is is water a reasonable approximation and one thing we can do and physiologists love to do this is to provide a sort of back of the envelope calculation just to see whether or not we're in the right ballpark like is this a reasonable model or not or are we missing something in our model for blood here well if we convert this uh concentration of oxygen until in into milliliters of o2 which is another convention in physiology we've got millimeters of we've got 0.8 milliliters of o2 in um in solution this is for water at atmospheric pressure 21 um or actually i should say sorry um so so this does correspond to atmospheric pressure um not necessarily the pressures that are shown up above so this is the concentration that we get because what we want to consider is whether or not at sea level uh water would be sufficient to transport oxygen okay so um let's actually replace water with plasma so plasma doesn't include red blood cells it's just all the proteins and the other chemistry that's in the blood and we're doing this to see if plasma provides a sort of enhancement in the solubility of oxygen in the blood and by the way this should be milliliters of o2 per liter of water so that slash should have an l to the right of it in plasma we find that actually yeah the solubility is um it's quite a bit better it's not as good as what we see for carbon dioxide but it's more than three times um better than water okay so there's something about those proteins and the other stuff that's mixed in the plasma it really helps all right so now we can pose the question is this enough is is the solubility of plasma enough to meet the metabolic demands of the body all right so here's where we get to our back of the envelope calculation we know from respirometry measurements that a body at rest needs 250 milliliters of o2 per minute okay so that makes sense because it's a quantity of oxygen per unit time it's not per liter because it's for the total body there's no particular volume that we're concerned with we just want to know what's the total amount of oxygen that we need per unit time so we've got a quantity here which is a concentration so how much oxygen per liter and we want to get something that's oxygen per unit time so we want to multiply this by something what makes sense let's see so units-wise it should be liters per minute so what's liters per minute oh okay i know the flow rate that is how much the blood how much blood is circulating through the circulatory system okay so we take our concentration of oxygen per liter provided this is what's provided by the plasma we multiply by the flow rate we can look that up so that's our liters per minute the product is 15 milliliters of o2 per minute in other words six percent of the metabolic demand all right so plasma does not provide sufficient oxygen delivery to the aerobic cells of the body all right so the big missing ingredient here are the red blood cells let's consider the chemistry of that so we're going to add to the plasma those red blood cells which are known as erythrocytes so we zoom in here this is what erythrocytes look like they don't have a nucleus and they are just packed with a really important molecule for this transport problem and that's known as hemoglobin hemoglobin includes iron in each of what are called heme groups the heme groups are really good at binding to oxygen so you can think of the red blood cells in this context as packages of hemoglobin each of which have four binding sites for four oxygen molecules and it's just packed with thousands upon thousands and the circulatory system is packed with the red blood cells so this is really the difference okay this is the difference between the sort of poultry performance of oxygen transport provided by the plasma and what the blood is actually capable of and the dynamics of hemoglobin turned out to be really important and also flexible they change under different physiological conditions through blood chemistry so let's consider that and we're going to do that by just considering blood in a dish so here we have a petri dish and we're going to fill it with blood and we're going to monitor how much oxygen is in solution and we're going to place our petri dish in a chamber that allows us to manipulate either the gas mixture or the total pressure that of of the the gas that comes in contact with the surface of the blood now this is important bear in mind the origin of the measurements that i'm about to present because we're going to make inferences about what happens in the lungs and what happens at the cells the exchange of gases at the cells all of this is inferred from a relatively simple experiment okay so just bear that in mind the nature of sort of the source of the measurements compared to what we're inferring it'll become a little bit clearer in a moment so here we have our measurements the x-axis is what we're controlling okay the partial pressure for o2 now we now know from dalton's law there's two ways you could do that you could vary the total pressure and keep the proportion of oxygen at 21 percent or you could keep total pressure the same but you could infuse a higher concentration of oxygen to boost its partial pressure you get the same result either way and then we're going to use our oxygen electrode to get the total saturation so if the oxygen electrode measures in terms of milliliters of o2 per liter of blood or maybe moles of o2 per unit volume something like that then that gets normalized by the maximum you know the the highest concentration of oxygen that we can get in the blood and the way that this curve looks and it's largely driven by hemoglobin if you remove hemoglobin from the blood and you just do this experimental plasma you don't get anywhere close to the same levels of saturation so really hemoglobin is where it's at that is the molecule that matters for oxygen transport so we go from a partial pressure of 40 millimeters of mercury to 100 millimeters of mercury 100 millimeters of mercury it turns out is the partial pressure encountered in the lungs that is the gas mixture in the lungs achieves something close to 100 millimeters of mercury so in this experiment that's what we're manipulating it's the gas above this interface with the blood and that's simulating at 100 millimeters of mercury what the blood is exposed to in the capillaries in the lungs given the air that's inspired in the lungs the blood then gets transported through the body it eventually finds its way into capillaries that provide vascularization for the cells that need it cells of the body commonly have a partial pressure of 40 millimeters of mercury so blood is going to be moving up and down this curve okay so initially when it becomes oxygenated it reaches equilibrium with the air in the lungs so it'll be at this level and then the blood eventually finds its way to the cells and it will move down this curve as diffusion drives oxygen from the blood to the cells that need it now the shape of this curve matters to that transport the shape in this part of the curve has a very slight slope and we'll see that compared to the other part of the curve in a moment but what a slight slope or a low slope on this curve means is that you need a really large increase in the partial pressure for o2 to go from this point on the curve that is 75 percent of saturated all the way up to a hundred percent saturated you have to traverse from 40 to 100 millimeters of mercury in order to get that last 25 percent of saturation now even though um i just told you that the cells commonly have partial pressure of 40 millimeters of mercury it is possible when you're really active for the cells to achieve a much lower partial pressure much less than 40 millimeters marker this would especially be common under intense exercise and we see that below 40 millimeters of mercury a very different slope here the slope is quite high and what that means is that a small decrease in partial pressure causes a really precipitous drop in saturation so we're going from 40 millimeters of mercury i don't know what that is like 10 millimeters of mercury so that 30 millimeters of mercury difference is much less than the 60 millimeters of mercury that we see between 40 and 100 uh it's half and despite that being a pretty small difference in partial pressure we get this huge drop in the oxygen saturation so on that part of the curve just a really small decrease in partial pressure effectively releases a lot of oxygen because the y-axis tells us how much oxygen is in the blood if it's not in the blood then it's released by the blood or in the air in the case of what's going on in the lungs so when the blood goes from 40 millimeters of mercury down to this level it's giving up that oxygen and making it available to the cells that need it so when the blood encounters an environment that is a very low partial pressure something like 10 millimeters of mercury then it's going to liberate oxygen and make it available to the cells now this relationship is known as the oxygen dissociation curve the partial pressure for o2 increases in the plasma and that causes hemoglobin to bind o2 all right that's that's just a statement about the nature of the measurement that we're making here that we're increasing the partial pressure in the plasma because we're exposing that plasma to an increase in partial pressure of the the gas that's above it now um let's get back to the shape of the curve affecting this exchange so just consider the exchange that occurs at the level of the cells it's not hard to envision what happens in the lungs right we just basically if we if the blood when it returns the lungs is a very low partial pressure then the capillaries in the lungs and their interface with the dissolved gas allows it to re-saturate back to 100 millimeters of mercury and then as it goes back to the exercising cells then the blood moves back down this curve okay so that brings us to what's happening on the left now initially the cells encountered by this parcel of blood are at 40 millimeters of mercury all right so that's right here where we said the cells are at that level all right so that's going to cause the um the blood to drop to a saturation of 75 so going from 100 in the in the lungs then it's dropping to 75 percent that means it's making oxygen available to the cell so when we look on the left that's what we see oxygen is liberated if it's not being held on to by the blood that means it's being made available to the cells and so as the red blood cells move through then it's oxygen for everybody all right now um our red blood cell and all the hemoglobin inside of it all the bound oxygen encounters some cells that are at a lower partial pressure all right 20 millimeters of mercury now because we're on the part of the curve with the steep slope that means there's a larger drop in saturation that means that more oxygen is made available to those cells that are exercising most intensely so this is why the shape of the curve matters if this were a linear relationship then any given drop in partial pressure would have the same amount of oxygen released by the blood instead this nonlinear relationship means that you get more oxygen liberated for a given drop in partial pressure here we see a drop between 40 and 20 all right so these 20 would be like right in here and we see a big drop you know something below 50 percent from 75 whereas a 20 millimeter of mercury drop on this part of the curve would just cause a change from like 100 to 90 something percent now another key point for the oxygen dissociation curve is that the shape of that curve also depends on other factors that change under healthy physiological conditions for example ph all right the ph drops when you exercise intensely we'll get to why that is the case in a moment but what we see here is that we have a drop in ph that means the green curve is a blood that is more acidic than the red curve let's just consider what happens at 40 millimeters of mercury so we have this is sort of typical for resting cells we're at a lower saturation level on the green curve than on the red curve so what that means is that the blood at a ph of 7.2 is going to be less saturated at 40 millimeters of mercury than the blood at 7.4 if it is less saturated that means that more oxygen has been released by the blood thereby making more oxygen available to the cells and that's what occurs when you're very active your blood ph will drop that will make the oxygen more readily available to those exercising skeletal muscle cells and this is true at all partial pressures you can see that the values of the green curve is less than the values of the red curve at every partial pressure so we can say the blood is less saturated at lower ph you get the same effect if there's an elevation in the partial pressure for carbon dioxide so you get that same kind of effect if the partial pressure for co2 is greater in the blood then the blood will be less saturated for o2 this matters at the level of the cells it also you also get the same kind of effect if the blood is at higher temperature again something that occurs in parts of the body that are exercising at high intensity all of these are driven by an elevation in activity and all result in the blood being less saturated with oxygen okay so this all matters to the exchange that occurs at the level of the cells not so much for the exchange that occurs in the lungs okay the partial pressure of co2 in the lungs is set by its exposure to the to the air that's inside of the lungs that also causes the ph to not be acidic and the temperature of the lungs should not be elevated uh even though it might be sort of warmed up a little bit by the blood but there is no elevated metabolism in the lungs like you see in the exercising skeletal muscle so all of these effects really matter for the exchange that occurs at the cells another point here is that uh you see a very large separation between these curves at a partial pressure that you would expect for the cells whereas um at the lungs that are at a 100 millimeters of mercury there's really very little difference between those two curves okay so this point about the effects of ph co2 and temperature really apply to the exchange that occurs that occurs in the cells and what it favors is the release of more oxygen when you are more active okay so everything i've described so far applies to the transport of oxygen to the cells but of course exercising cells and even resting cells that are using aerobic metabolism produce co2 so how is co2 transported we see that hemoglobin is really really important for o2 and it really dominates o2 transport what about co2 well let's consider the exchange of the cells on the left and the exchange the lungs on the right just to consider what happens to co2 that's in the blood now co2 has some like oxygen low level capacity to just diffuse into plasma and be transported in the plasma itself that only accounts to seven percent of the transport now when um when red blood cells encounter cells that need oxygen and it releases oxygen then hemoglobin itself can bind co2 and that accounts for almost a quarter of co2 transport is binding to the hemoglobin in the red blood cells so we think of red blood cells as being oxygen transporters they also it turns out transport a fair amount of co2 now another thing that occurs in the red blood cells is the conversion of co2 into bicarbonate and this is the most popular means of transporting carbon dioxide what does that conversion look like well now i've mentioned ph a couple of times this is the reason why blood ph changes and it also provides the means for the lungs to influence blood ph now excuse me carbon dioxide and water in solution produces carbonic acid so if you have a higher and higher concentration of co2 then you you just produce more and more carbonic acid that in turn is converted into bicarbonate and a proton and it's that proton proton that lowers blood ph so effectively in the exercising cells when there is an elevation in carbon dioxide that results in more carbon dioxide in solution we go through this reaction that produces a high concentration of protons and also bicarbonate and that serves to lower the blood ph the blood ph is lower in exercising cells than what you see in the exchange that occurs in the lungs because in the lungs you essentially have a reversal the bicarbonate that is transporting co2 is converted back to carbon dioxide and water and this just occurs naturally as there's a reduction in the partial pressure for co2 as it is exposed to the air in the lungs then there's a reversal of this reaction and so blood ph will rise at lungs because we're taking those protons and in combination with bicarbonate we produce water and co2 the co2 then diffuses into the lungs so in summary we have this question of how can gas exchange be maximized and we saw a variety of physical principles there's the ideal gas law which indicates that if you reduce the volume for a fixed number of gas molecules or you change the number of gas molecules then you can elevate exchange that's then basically boyle's law is the product of the pressure and the volume maintaining remaining the same as you change the volume it's essentially an application of the ideal gas law and dalton's law articulates the partial pressure so if the partial pressure is greater then you have more of a driving force of a gas like oxygen into solution now on the receiving end blood chemistry really matters because it affects the solubility of o2 in solution so you get the driving force provided by partial pressure but then the amount that moves into solution depends on the solubility so hemoglobin's really dominant for o2 and that's reflected by the oxygen dissociation curves which also vary with blood chemistry ph temperature and partial pressure for co2 and then finally we have carbon dioxide transport through multiple amines 70 of which comes from bicarbonate now the big picture here is that this exchange works really well and i should say the lungs work really well uh if you look at the partial pressures in solution now partial pressures as i've mentioned the the the quantity has to do with it with what occurs in gases but it's a convention in physiology to talk about the concentrations of the gases in solution in terms of partial pressure so in the blood you can have a partial pressure this is not actually a pressure that's generated in the blood all right that has more to do with all of what we said about partial pressure systolic diastolic all the stuff for the left ventricle the elasticity of the major arteries all that kind of stuff is the actual measured pressure but when blood is exposed to gas a gas of 100 millimeters of mercury then it will adopt a certain number of moles in solution a certain concentration okay so this is somewhat uh non-intuitive because we're using the term pressure here for what occurs in a liquid but it's not actually mechanical pressure it's just the concentration that corresponds to what you generate from this partial pressure anyway it's a long-winded answer to say that the partial pressure in the blood it reflects a concentration of a dissolved gas so the blood that leaves the lungs that's through the pulmonary vein has a partial pressure for oxygen of 100 millimeters of mercury co2 40 millimeters of mercury and that's exactly what gets transported to the cells the fact that it moves to the left heart doesn't matter the cells have about 40 millimeters of mercury for o2 a higher value of 46 millimeters for mercury of co2 then the cells reach equilibrium with the blood so that the blood leaving the cells has the same partial pressures that is in the systemic veins the blood then moves through the right heart onto the pulmonary artery artery you see exactly the same levels there okay then what the lungs do is essentially go from 40 millimeters of mercury for o2 to 100 and then we see an offloading of co2 so that it goes from 46 to 40. and what i want to emphasize here is the nature of the exchange okay these are the values of partial pressures for the air that's inspired into the lungs or i should say the gas mixture by the time it makes it into the lungs has a hundred millimeters of mercury for o2 and 40 millimeters of mercury for co2 so what the lungs do is essentially just get the blood in close proximity to the gas mixture so that the partial pressure in the blood matches that gas mixture it matches what's in the air same thing for the cells we see that the partial pressure for blood in the veins ends up equaling exactly what's in the cells the capillaries just get the blood really close to the cells and they reach equilibrium okay so our transport of dissolved gases is not done in a way where we can boost our partial pressure for o2 in solution any higher than what the um the air provides and in the cells we also cannot have any kind of a mismatch all right so the kind of exchange that's provided for dissolved gases like in the lungs and the cells is what we'll see later is very different for what you have for the digestive system where you end up taking up more nutrients in the blood than what we end up pooping out of our bodies and in the kidneys where we can provide a different solute concentration in the urine from what's in the blood so those are very different exchange organs than what we see for the respiratory system more on that later