Hello, we're going to move to talking more about C02 and how it is carried in the blood. Then towards the middle, we will switch to talking about ventilation- perfusion mismatch and what that means for a normal lung. So, we've talked about how oxygen is mostly bound to hemoglobin, 98 to 99% of it and only a very small, 1 to 2% is dissolved in blood. A similar scenario is true for CO2, where as it dissolves as a gas in plasma, that only accounts for 10% of CO2 in blood. CO2 can bind to hemoglobin, in particularly deoxyhemoglobin. It has a higher affinity, and so that will also account for a significant portion of CO2 in blood will be that it's bound to hemoglobin. But most of CO2 in blood, 60%, will be as bicarbonate ion. This set of chemical reactions right here, is important for you to commit to memory because we're going to be talking about it for the rest of our time studying the respiratory system. Then we will come back to it, when we talk about the kidneys and their regulation of acid-base balance. The reason why CO2 gets converted to bicarbonate is because of these reactions. Water and CO2 can combine through the action of carbonic anhydrase, an enzyme that helps convert water and CO2 to carbonic acid. Carbonic acid will then disassociate into bicarbonate and a proton. So that means that, and we will see this in a figure in a moment, when the blood comes to the tissues, and CO2 enters the blood that is going to force these reactions to the right. Because we're increasing the amount of CO2, which means that we produce more bicarbonate and more protons. So you can keep that in mind, that whatever happens to CO2 is going to cause an increase in bicarbonate, and increase in protons. Similarly if we have an increase in protons then we're going to move the reactions this way. We're going to have increased CO2. We're going to talk about this more and more, but keep that in mind that that's these reactions are going to be present and will affect the amount of CO2 versus the amount of acid and therefore the pH throughout the rest of our discussion. Again this is a view of what's going to happen. In the tissues we will have a pressure of CO2, let's say of about 46 but in the blood, only a pressure of 40. So we have a gradient for CO2 to diffuse into the blood. Some of it will just stay dissolved in the blood. We will also have a gradient for CO2 to enter the red blood cell. Again, some of it will be able to be dissolved in the red blood cell, some of it will bind to CO2, I'm sorry, to hemoglobin, and then a large portion, about 60% of it, will be converted to bicarbonate. When we get to the lung, we will have a gradient where CO2 is higher in the blood than it is in the lung. So, CO2 will diffuse into the lung. That's going to cause CO2 to diffuse out of the red blood cell, and cause it to also be removed from hemoglobin. This also causes bicarbonate and protons to combine to form H2O and CO2. The CO2 will diffuse into the alveolus. We're going to now switch gears a little bit and talk about what's called V/Q mismatch, ventilation and perfusion. So the V is for ventilation and the Q is for perfusion. The idea is that even though we've been talking about the lung as if it is the same in all regions, that actually it is not. This is due mostly to just gravity. Let's consider this. Where we're looking at depends on where we are in the lung. If we are in the bottom of the lung or the top of the lung, both ventilation and blood flow, or Q in the perfusion, changes. What that means, in terms of unless they are perfectly matched, then we're not going to have perfect exchange. Let's consider ventilation first. We know that our lung is really kind of hanging in the chest wall. What that means is that the top of the lung is stretched more than the bottom of the lung because its got the rest of the lung hanging from it. That affects is the compliance. Where you can see with this slinky, the top is already stretched, so it's lost some of its compliance, whereas the bottom of the lung, since it just hangs there, has increased compliance. It's much more distensible. Because of that, that means that the ventilation is decreased at the top of the lung, and increased at the bottom of the lung. So at the bottom of the lung where there’s increased compliance, then we have increased ventilation. That’s what we see on this graph. Ventilation is greatest at the bottom of the lung. It’s not a huge effect with ventilation, but it is an effect. With blood flow, we see a larger effect. The slope of the line is much more steep. But it is still in the same direction, where at the bottom of the lung we have greatest blood flow. There is a couple reasons for that. One, is again due to gravity, and the fact that the bottom of the lung is below the heart. So blood is going to tend to, not necessarily pool, but be present in larger flow amounts at the bottom of the lung. The other issue is that we've already looked at how the lung tissue itself will change from the bottom to the top. How that these, since they're more stretched, at the top of the lung, the alveoli are more stretched. This is why their compliance is less. That also means that the capillaries between the alveoli, are more compressed. So that's another effect of really gravity on the lung. It compresses the vasculature in the top of the lung which again is what makes such a dramatic difference in the blood flow at the bottom of the lung versus the top of the lung. So both ventilation and perfusion are increased at the bottom of the lung. But you see, because the slope of the ventilation is not very steep, and the slope of the blood flow is steeper, that the lines cross. Which means that the V/Q ratio is greater than one at the top of the lung because ventilation is greater than profusion. But the V/Q ratio is less than 1 at the base because of the fact that now blood flow is increased over ventilation. So the V/Q ratio swaps from being less than one to more than one, when you go from the top to the bottom. But in both cases, blood flow and ventilation are greater at the bottom of the lung. We are talking about a normal lung. So in all of us, with a normal lung the V/Q ratio of is in general 0.8. It's not a perfect machine in terms of V/Q mismatch. Now there are also many disease processes that can effect V/Q mismatch even more dramatically. That's what this diagram refers to. For instance, we could have decreased blood flow. It could be because we have a blood clot or an air bubble in a blood vessel that's leading to a portion of the lung. When that happens, then the pressure of carbon dioxide in the alveolus is going to decrease because remember if blood can't flow to that portion of the lung, then CO2 is not going to be delivered, and there's really low CO2 in the atmosphere. So without that CO2 coming from the blood, the pressure of CO2 will be low. So the blood, the body senses this, and says okay for some reason I'm not receiving blood flow, what I'm going to do is cause bronchoconstriction, which doesn't make so much sense unless you think about the fact that then that allows the air that was going to that part of the lung to go to a different part of the lung where it can actually be used. There's no point in wasting that air that's coming in to that part of the lung if it's not getting exposed to blood. Instead it gets diverted to another part of the lung that is healthy. A similar thing happens if we have decreased air flow. Let's say you inhale something that blocks one of your bronchioles so that a small portion of the lung can not get any fresh air. That will result in the pressure of oxygen in the capillaries that feed that part of the lung to decrease. Again, the body says, for some reason we're not getting ventilation to this part of the lung. That's just a waste, so let's now have vasoconstriction. Which will allow the blood to be diverted to a different part of the lung where there is proper ventilation. This is very interesting because you've already heard about in the cardiovascular system from Dr. Jakoi, how if the pressure of oxygen goes down, then you're going to get dilation of the vessels to try to increase blood flow. Here in the lung, because it's function is different, we're get the opposite effect. Low oxygen actually causes vasoconstriction. This system can pose a problem for people when we have situations like really high altitude. Now we've got basically the very similar case of decreased airflow, because the pressure of oxygen in the atmosphere is much lower. The lung senses this because of a reduced pressure of oxygen, in the capillaries. The problem is that it is true for the whole lung. Because the O2 is decreased in the the air that's being breathed. That can cause a kind of universal vasoconstriction in the lung. This will cause the pressure to increase so much that the capillaries start leaking and then cause massive pulmonary edema which then is going to make the problem even worse in terms of trying to breathe because now we've increased the diffusion barrier. So not only is the oxygen low in the atmosphere, what little is there is going to have much more difficult time diffusing into the blood. This is what's called, what happens in high altitude pulmonary edema. When this V/Q mismatch compensation goes wrong. There are some people that are more susceptible to high altitude pulmonary edema, but the response is based on this response, the V/Q mismatch. The problem comes when the whole lung responds to that, responds in that way, and then if you have leaky capillaries. So we've talked about how we have carbon dioxide, it's soluble in blood, so it's not going to need a carrier like oxygen needs hemoglobin, but, and it also means that carbon dioxide is going to be very proportional to minute ventilation, whereas oxygen is going to be less proportional, because you've got the effect of how much oxygen is on hemoglobin. Which does not change linearly with the change in pressure of oxygen in the blood. The arterial blood gases are going to give a monitor for the adequacy of perfusion. Even in a normal lung function, we're going to have to worry about trying to match ventilation and perfusion. It's not going to be perfect. And we can, we have compensatory systems built in to try to keep ventilation and perfusion as close as possible.