Welcome back. We are starting our fifth video about the respiratory system where we're going to now move to talking about what's going to happen more specifically with the gases in the alveloi and then once they get into the blood. So we're slowly moving through the process of exchange between the alveoli and the capillaries. We will be talking about oxygen transport mostly today. First, we're going to consider how we can calculate what the pressure of oxygen is in the alveoli. This we know is important because, as we've already said, the oxygen pressure in the alveoli is basically the same as the oxygen pressure in the blood, unless there is a some sort of disease process, which will talk about later. So, it's very important to determine what the alveolar pressure of oxygen is because that should be what the pressure of O2 in the arteries. However, we can't measure it directly. That's the other issue. Because of these reasons, we use the alveolar gas equation. The idea is that we can measure in arterial blood the pressure of oxygen and the pressure of CO2. Then we can use those pressures to help us calculate the pressure of oxygen in the alveoli. The alveolar gas equation basically takes into account three things. One is this first term. It is the pressure in the air that we're breathing. We've already talked about this, where we're going to consider what's the fraction of the inspired air that is oxygen. Then we also have to take into account the fact that we are adding water vapor as that air comes in. So, we have to consider the pressure of the atmosphere where we are, the percent that oxygen is in that atmosphere, and then subtract out the added water vapor. We know already that that's going to be 150 mL of mercury when we're at sea level. Then, just like we had to say that the pressure of oxygen is going to decrease when we add water vapor, similarly when we're in the alveoli, lots of CO2 is being added, particularly in comparison to how much CO2 is in the atmosphere. And so, we have to subtract the pressure of CO2, which will reduce the pressure of oxygen in the alveoli. That is going to be what happens in the second term of our equation where we're going to subtract out, instead of the alveolar CO2, which, again, we can't measure, but it's going to be very similar to the arterial CO2. So, we will instead substitute the alveolar pressure of CO2 with the arterial pressure of CO2. That will let us know the alveolar ventilation rate, how much we're breathing, which we'll talk about in a minute as well. So, the second term in our equation, instead of being alveolar CO2 is going to be arterial CO2, but that should be a good estimate. And then, there's another issue which we haven't talked much about and we're not going to talk about too much, is the fact that, based on our diet, that's going to affect how much CO2 we're producing versus how much oxygen we're consuming. That is called the respiratory quotient. The amount of CO2 that we produce versus the amount of O2 that we consume. In someone who has a mix diet, then mixed means carbohydrates, proteins, and fats, that's going to be 0.8. If you are on an exclusively carbohydrate diet, that ratio would be 1. But in a mixed diet that's going to be 0.8. That's going to factor in to how much oxygen is present as well when you are considering CO2. How much CO2 is being produced versus oxygen being consumed. As we've said, this alveolar gas equation's important because we can't measure the oxygen in the alveoli, and we know that the arterial should match up to the alveolar oxygen pressure in normal circumstances. Let's also consider how ventilation is going to change the pressure of oxygen versus CO2 as well. We know that under normal breathing conditions, that the pressure of oxygen in the alveoli should be 100, and the pressure of CO2 should be 40 millimeters of mercury. If we deviate from that for some reason, then those pressures of both oxygen and CO2 are going to change. If we hyperventilate, say that you're having some sort of panic attack, and so you end up breathing more than you really need to, then what you're doing is hyperventilating. The definition of that is that, then, the CO2 will be decreased in the blood because now you're breathing more than you really need to, which means that you're removing more CO2 from the blood. Similarly, the oxygen will be changed, but instead it will increase because now you're bringing in more fresh air that has more oxygen. You're replacing more of the air in the lung with fresh air that has a lot of oxygen. So, really, the definition of hyperventilation is that you have a decreased pressure of CO2 in the blood, but then as a result often the oxygen is also going to increase in the blood. Then we can also have hypoventilation. It might be because you took a certain drug. Too much of a certain drug that caused you to stop breathing as much as you should. So, the definition of hypoventilation is that now you're going to have increased PCO2 in the arterial blood because you're not removing the CO2 as much as you normally do, which means it's going to start accumulating. Which is what's happening here. Then, for the oxygen, that's going to decrease as you're not bringing in as much fresh air, but you're still consuming just as much oxygen as you were before. And so, the pressure of oxygen in the blood will decrease. We'll talk more about these changes in the pressures of oxygen and CO2. Another thing to consider is what happens at the alveoli? We have a single alveolus here. And we will have a capillary that runs along its length. We know that the blood, before it reaches the respiratory portion of the lung, before it reaches this alveolus, that the oxygen pressure is going to be about 40 millimeters of mercury. The question is where along the length of this capillary is the blood going to have equilibrated with the oxygen in the alveolus which we know is roughly a 100 millimeters in mercury? That's what this graph is showing, we're starting at 40 and what point along the capillary are we reaching 100? You can see that is about a third of the way along the length of the capillary, is the point where we've already reached 100 millimeters of mercury of oxygen. That we've already had complete equilibration. This really points out the large what we call safety factor in the system, where even if we exercise very strenuously, we're still going to be able to completely equilibrate the blood oxygen with the alveolar oxygen. So if we exercise really vigorously and we have greater blood flow to the lung, we're still going to be able to equilibrate the oxygen which is of course going to be extremely important. So this is not going to be an issue with exercise. It's not going to be a problem of the respiratory system, when we exercise. However there can be states when if particularly, if diffusion is limited for some reasons. So, say that you have a pulmonary edema. This means you have fluid in your lungs, which we'll talk about in later sessions. That fluid will greatly increase the distance that oxygen is going to have to travel to get from the alveolus through that liquid and then into the capillary. And so in states like that we can have disease states that do limit diffusion. If that occurs then that's going to limit the pressure of oxygen that can be attained into the blood. That's going to be a very serious issue when that occurs. We're going to switch gears a little bit now and now start talking more about the blood side. So far, we've been talking about the pressure of oxygen in the blood. If we say that we have two chambers with oxygen in them with a membrane separating them as we do here on the left, then oxygen moves easily across membranes thankfully. And so the pressure of oxygen in both chambers will equilibrate very rapidly. So that the pressure of oxygen in both chambers is equal. Now if we add hemoglobin which is going to be a protein that is highly abundant in red blood cells that that can bind O2 to each hemoglobin subunit. Hemoglobin binds four oxygens. It is a protein that binds oxygen. If we added it to one of the chambers, then it will bind oxygen in that chamber. And then when we talk about the pressure of O2, we're talking about either the pressure of O2 in the air, in the alveolus, or we're talking about the pressure of oxygen that is dissolved in the blood. That's what we've been talking all along about, is the amount of oxygen and its pressure that's just dissolved in the blood. That's the only thing that PO2 means. As we add the hemoglobin and it binds oxygen, that oxygen is not longer simply dissolved in the fluid. It is no longer a part of the pressure of oxygen in that chamber. So even though we still have the same number of oxygens, we still have six oxygens in the left chamber and six in the right, the pressure of oxygen in this left chamber has now decreased. It's only three oxygens versus six over here. Then what will happen as a result is that oxygen is going to now diffuse into this left chamber. Because diffusion is going to be based on the pressure of oxygen not the content of oxygen. And so what that means is then we will finally reach equilibrium where we have equal pressure of oxygen in each chamber. They both have two molecules. However the content of oxygen is much greater in the chamber that contains hemoglobin. And so, you can see that clearly because now hemoglobin is fully bound with its four oxygens. We have a much greater oxygen content in the chamber on the left. That means that when we taken to account, the concentration of oxygen in the blood, we have to take into account, the pressure of oxygen which is the dissolved oxygen, but also the amount of hemoglobin, and how saturated the hemoglobin is with oxygen. Those three characteristics of blood are extremely important. The other thing to keep in mind is that 98% to 99% of oxygen in blood is going to be bound to hemoglobin. So that when referring to the pressure of oxygen in blood, we're only referring to 1% to 2% of the oxygen in blood. Because the oxygen is not so soluble in blood. But luckily, we have hemoglobin, which is high in abundance in red blood cells and binds strongly to oxygen to greatly increase the content of blood. So keep in mind that when we're talking about the pressure of oxygen, we're only talking about 1% to 2% of the oxygen in the blood. But as we'll see in the next figure if we know the pressure of oxygen, we also know what the saturation of hemoglobin is going to be with oxygen which tells us a lot as well. Also keep in mind that as we talk further about how the body is going to monitor oxygen in order to control ventilation. It's also monitoring the pressure of oxygen. Not how much oxygen is present on hemoglobin, at least in terms of controlling breathing. So someone who's anemic, who has fewer red blood cells and may have a dramatically reduced oxygen content of their blood. Actually their body has, doesn't detect that to modify breathing because the body is monitoring the pressure of oxygen in the blood. We'll talk more about that in future sessions. So that means that, What's going to happen when the blood gets to the lung, so we know the pressure of oxygen in the lung is going to be 100 millimeters of mercury. And in the venous blood coming into the lung, it's going to be 40 millimeters of mercury, the pressure of oxygen. So, oxygen is going to have a huge gradient to defuse into the blood, and then in the red blood cell, it's going to be 40 millimeters of mercury. So, it's going to be a huge gradient for oxygen to defuse into the red blood cell, and then, it's going to get bound by hemoglobin. Which remember removes it from being part of the pressure of oxygen. Removes it from kind of the gradient so that we're going to have a large gradient for oxygen to enter the red blood cells because it keeps getting bound by hemoglobin. Until finally the hemoglobin gets saturated and then the red blood cell will equilibrate and become 100 millimetres of mercury as will the arterial blood. When we get to the tissues, we're going to have the opposite case so let's just say this blood just came from the lung. It's still got 100 millimeters of mercury, of oxygen as does the red blood cell. The tissues, let's say it's about 40, so we've got a huge gradient from, for oxygen to leave the blood and go to the tissues. That's going to lower it's gradient, lower it's pressure of oxygen, let's say to 90 which is then going to give a gradient for oxygen to leave the red blood cell and then that will cause oxygen to come off of hemoglobin. And so that will continue as this blood continues to flow through capillaries until everything comes back to 40 in the red blood cell and in the blood in terms of the pressure of oxygen. However, we'll see that does not mean that all the oxygen is off of hemoglobin. There's still be plenty of oxygen on hemoglobin because even at the pressure of 40 millimeters of mercury, hemoglobin still contains a fair number of oxygens, that's what this curve is showing. So this is showing at different pressures of oxygen that are dissolved in the blood, what does that mean for how saturated hemoglobin is? So we have some pressures that we're used to talking about. We know that arterial blood is going to have a pressure of oxygen of 100 millimeters of mercury. So not surprisingly at that pressure hemoglobin is going to be basically fully saturated. It's going to be basically all of its sites are going to be bound by oxygen. As we move to a pressure of oxygen of 40 millimeter of mercury that's when the hemoglobin will be about 75% saturated. So under normal conditions when you're just at rest, by the time your hemoglobin gets back to the lungs it will have dropped off 25% of its oxygen. But it still has the majority of its oxygen. This gets into again this idea of a safety factor, were that means that if you do start to exercise, which means that especially in the muscle that the pressure of oxygen is going to go even lower than 40. Then we will lose even more of our oxygen so that we can get down to 25% only 25% of the oxygen is left on hemoglobin. You can see in this part where we're just at rest with a venous pressure of 40 millimeters of mercury to when we're at exercise, this is a very steep part of the curve. Where just a small drop in the pressure of oxygen, means a lot of oxygen gets released from hemoglobin. And so this is a part where small changes in pressure are going to lead to big changes in delivery of oxygen. The other place where we have a safety factor is up here where the hemoglobin remains basically fully saturated, well below the pressure that we normally are living at, at least a lot of us. When we're at sea level and we have then a pressure of oxygen of about 100 millimeters in our arterial blood. If we go to higher altitude so say that now we're, the pressure of oxygen is 60 millimeters we still have hemoglobin that is highly saturated with oxygen. So, this again is another safety factor where we can go to environments that have less oxygen and still have a hemoglobin that's very close to being saturated. Since hemoglobin is a protein, then its environment can slightly change its confirmation that then affects its affinity for oxygen. And so this is going to be used by the body to either help load the hemoglobin to help load the hemoglobin or help release and dump oxygen from the hemoglobin. And so when this happens, then the curve shifts, the hemoglobin oxygen dissociation curve shifts. And as it shifts to the left, then as you can see at a certain pressure, now hemoglobin is more saturated. Which then means that the left shift of the hemoglobin curve is favoring loading of the hemoglobin. This occurs when a baby is a fetus in it's mother and it is expressing a different hemoglobin called fetal hemoglobin which has a higher affinity for oxygen, has basically a left shift of the curve. This is important because the mother is sending its blood to the baby and the baby must draw the oxygen out of the mother's blood with its fetal hemoglobin. And so, the fetal hemoglobin has a higher affinity for oxygen then it will be able to take that oxygen off of the maternal hemoglobin. So that's one example of a left shift of the hemoglobin curve. Mostly we're going to be talking about right shifts of the curve which are then going to favor loading, I'm sorry unloading, where here we can see if we right shifted the curve, that then the hemoglobin will have dumped more of its oxygen. So there are several conditions that are going to cause a right shift at the curve, and a lot of these make sense. So, in terms of when you're exercising and your muscles, they're often going to have increased CO2, pressure of CO2. And they're going to have increase temperature and they're going to be producing acid and so they're also going to have a low pH. All of those things are going to cause a right shift so that when hemoglobin travels through those tissues and has its conformation adjusted by these increase CO2 temperature and low pH. Then it will dump more of its oxygen, becuase it will be right shifted. Another factor in causing a right shift is 2,3-diphosphoglycerate, which is a metabolite that is found in red blood cells, particularly when people are at higher elevation. Or when they're doing an aerobic exercise, then levels of 2,3DPG increase which again causes a right shift so there can be more dumping of oxygen from hemoglobin. So we've now talked about how we can determine what the pressure of oxygen will be in the alveoli. And we've seen the diffusion rate as the blood is whizzing by the alveoli is very rapid, so that's not a limiting factor in terms of exercise. And that even though we talk about the pressure of oxygen in blood, that's a very, very small, only 1 to 2%, of oxygen in blood is dissolved. The vast majority of O2 is going to be bound to hemoglobin and that's very important because it increases the concentration of oxygen in blood dramatically since O2 not so soluble in blood.