So we've thought a little bit about the lungs and the tissue, and how there is a kind of (...sing?) relationship between the two, where they're trying to send little molecules back and forth, so long it try to send, of course oxygen, out to the tissues, right. And the tissue is trying to figure out a way to efficiently send back carbondioxide. So these are the --the kind of core things are going on, between the two. And remember in turns of getting oxygen accross, there're two major ways we said. The first one, kind of the easy one, is as dissolved oxygen --dissolved oxygen in the blood itself. But that's not the major way. The major way is when oxygen actually binds hemoglobin --in fact, we called it HbO2, and the name of that molecule is oxyhemoglobin. So this is kind of how the majority of the oxygen is gonna get delivered to the tissues. And on the other side, coming back from the tissue to the lungs, you've got dissolved carbondioxide, little bit of carbondioxide actually literally comes just right in the plasma. But that's not the majority of how carbondioxide gets back. The more effective ways of getting carbondioxide back, remember we have this protonated hemoglobin. And actually --remember when I-- when I said there's a protonated hemoglobin, there's gotta be some bicarb floating around in the plasma. And the reason that that works is because, when they get back to the lungs, the proton --the bicarb, actually kind of meet up again, and they form CO2 and water, and this happens because there's an enzyme called carbonic-anhydrase, inside of the red blood cells. So this is where the carbondioxide is actually gets back. And of course there's the third way, remember there's also some hemoglobin that actually binds directly to carbondioxide in the process, you know, it forms a little proton as well, and that proton can go to this bussiness, right? It can bind to a hemoglobin as well. So, there's a little interplay there, but the important ones I want to really kind of focus in on, are the fact that hemoglobin can bind to oxygen and also in this side, that hemoglobin actually can bind to protons. Now the fun part about all this is that there's a little competition, right? A little game going on here. Because you've got --on the one side you've got hemoglobin binding oxigen, and let me draw it twice, and let's say this topple an interaction with proton, well that proton is gonna wanna snatch away the hemoglobin. And so there's a little competition for hemoglobin, and here the oxygen kind of gets left out in the cold, and the carbondioxide does kind of the same thing we said. We-- Now we've little hemoglobin bound a carbondioxide and makes a proton in the process, but again, that leaves oxygen out in the cold. So depending on whether you have a lot of oxygen around, if that's the kind of key thing going on, or whether you have a lot of these kind of products, the proton or the carbondioxide. Depending on which one you have more of, floating around in the --in the tissue, in the cell, will determine which way the reaction goes. So keeping this concept to mind, then I could actually step back and say, well-- you know, I think that oxygen is affected by carbondioxide and proton, so I could say, well, these two --carbondioxide and protons, are actually --affecting, let's say are affecting, the --let's say, the affinity, the affinity or the willingness of hemoglobin to bind --of hemoglobin-- four oxygen. Right, that's one kind of statement you could make by looking at that kind of competition, and (the repressing?) come along in that they say, well, I think oxygen actually is affecting, you know, depending on which one --which perspective you take, you get the oxygen is affecting, maybe the affinity of hemoglobin for the carbondioxide and proton. --of hemoglobin for CO2 and protons. So you could say it from either perspective, if I wanna point out is that actually in a sense both of these are true, In a lot of times we think, well, maybe it's just saying the same thing twice. But actually, these're two separate facts, and they have two separate names. So, the first one, talking about carbondioxide and protons, their effect is called the {Bohr Effect}. See, you might see that word, or this description, This is the Bohr Effect. And the other one, kind of looking at from the other perspective, looking at from oxygen perspective, this should be the {Haldane Effect}. That's just the name of it, Haldane Effect. So, what is the Bohr Effect and the Haldane effect, other than simply saying that the things compete for hemoglobin? Well, let me actually bring up a little bit of the (can?) list, and let's see if I can diagram this out. because sometimes I think a little diagram would really go along when explaining these things. So, let's see if I can do that. Let's use a little graph and see if you can illustrate the Bohr Effect on this graph. This is the partial pressure of oxygen, how much it dissolved in the plasma. And this is oxygen content which is to say how much total oxygen is there in the blood, and this of course takes an account mostly the amount of oxygen that's bound to hemoglobin. So what if I slowly increase the partial pressure of oxygen, see how initially not too much is gonna be binding to the hemoglobin, but eventually as a few of the molecules bind, you get cooperativity, and so then slowly the slopes start to rise, becomes more steep. And this is all because of cooperativity, oxygen likes to bind where other oxygen have already bound. And then it's gonna kind of level off. And the leveling off is because hemoglobin is starting to get saturated. So there aren't to many extra spots available, so you need a lot --a lot of oxygen dissolved in the plasma, to be able to seek out and find those extra remaining spots on hemoglobin. So let's say we choose two spots. One spot, let's say, is high amount of oxygen dissolved in the blood, And this, let's say, is a low amount of oxygen dissolved in the blood. I'm just kind of choosing them arbitrarily, and don't-- don't worry about the units. And if you are to think of where in the body would be high location, that could be something like the lungs, where you have a lot of oxygen dissolved in bloods. And low would be, let's say, the thigh muscle where there is a lot of CO2, but not so much oxygen dissolved in the blood. So these could be two parts of our body, and you-- you can see that, now if I wanna figure out-- looking at this curve, how much oxygen is being delivered to the thigh. Then that's actually pretty easy, I could just say, well, how much oxygen was there in the lungs --or in the blood vessel leaving the lungs-- And there's this much oxygen in the blood vessels leaving the lungs. And there's this much oxygen in the blood vessel leaving the thigh. So the difference wherever oxygen is between this two points, that's the amount of oxygen that I got delivered. So if you want to figure out how much oxygen got delivered to any --any tissue, you can simply substract these two values. So that's the oxygen delivery. But looking at this you can see a kind of interesting point, which is that if you want it to increase the oxygen delivery, let's say you want it, for some reason, to increase it, become more efficient, then really the only way to do that is to have the thigh kind of become more hypoxic, as he moves to the left on here, that's really becoming hypoxic, or having less oxygen. So if he becomes more hypoxic, then yes --you'll, you'll have, you know, maybe, a lower point here, maybe a point like this, and that would mean a larger oxygen delivery. But that's not ideal, you know, when your thighs to become hypoxic, you know that --that could start aching and hurting. so is there an another way to have a large oxygen delivery without having any hypoxic tissue, or tissue that has a low amount of oxygen in it? And this is where the Bohr Effect comes into play. So, remember that Bohr Effect is that CO2 and proton affect the hemoglobin affinity for oxygen. So let's think of a situation --I'll do it in green, and in this situation we have a lot of carbondioxide and proton, the Bohr Effect thought is, that it's kind of a bit harder for oxygen to bind hemoglobin. So if I was to sketch another curve, initially, it's gonna be even less impressive, with less oxygen bound to hemoglobin. And eventually, once the --once the concentration of oxygen rises enough, it will start going up up up, and it does bind hemoglobin eventually, so it's not like it'll never bind hemoglobin in the presence of carbondioxide and protons, but it takes longer. and so the entire curve looks shifted over. This-- these conditions of kind of high CO2 and high proton, that's not really relevant to the lungs. The lungs will think you --for us, you know-- "who cares, we don't really have these conditions". But for the thigh, it is relevant. Because the thigh has a lot of CO2 and the thigh has a lot of proton. Again, remember, high protons means low pH. So, you can think it either way. So in the thigh, you're gonna get, then, a different point. Right, it's gonna be on the green curve, not the blue curve. So, we can draw it at the same O2 level, actually being down here. So what is the O2 content in the blood that's leaving the thigh? Well then, to do it properly out, they'll-- you'll be, actually you'll be over here. This is the actual amount. And so O2 delivery is actually much more impressive. Look at that. So O2 delivery is inceased because of the Bohr Effect. And if you want to know exactly how much it increase, I could even show you, I could say, well this amount from here down to here, literally the vertical distance between the green and the blue lines, so this is the extra oxygen delivered because of the Bohr Effect. So this is how the Bohr Effect is so important and actually helping us deliver oxygen to our tissues. So let's do the same thing now, but for the Haldane Effect, and to do this, we actually have to switch things around, so our units and our axis are gonna be different. So we're gonna have the amount of carbondioxide there, and here we'll do carbondioxide content in the blood. So let's think through this kind of carefully. Let's first start out with increasing the amount of carbondioxide slowly but surely, and see that the content goes up. and here, as you increase the amount of carbondioxide, the content just kind of goes up as the straight line. And the reason it doesn't take that S-shape that we had with the oxygen, is that there is no cooperativity in binding the hemoglobin. It just kind of goes up straight. So that's easy enough. Now let's take two points like we did before. Let's take a point --let's say, up here this'll be high amount of CO2 in the blood, and this'll be a low amount of CO2 in the blood. So you'd have a low amount, let's say right here, in what part of tissue? Well, low CO2, that sounds like the lungs, there is not too much CO2 there. But high CO2 probably is the thighs, 'cause the thigh is like a little CO2 factories, right? So the thigh has a high amount, and the lungs have a low amount. So, if I wanna look at the amount of CO2 delivered, we do it the same way with -- okay, well the thighs had a high amount, this is the amount of CO2 in the blood, remember. And this is the amount of CO2 in the blood when it goes to the lungs. So, the amount of CO2 that was delivered from the thigh to the lungs, is the difference --and so this is how much CO2 delivery were actually getting. So just like we had O2 delivery, we have this much CO2 delivery. Now, read over the Haldane Effect, and let's see if we can actually sketch out another line in the presence of high oxygen, what's gonna happen? Well, if there is a lot of oxygen around, then it's gonna change the affinity of hemoblobin for carbondioxide and protons. So it's gonna low less binding of protons and carbondioxide directly to the hemoglobin. And that means that you're gonna have less CO2 content, for any given amount of dissolved CO2 in the blood. So that line is still a straight line, but it's actually --you notice it's kind of sloped downwards. So where is this relevant? Where do you have a lot of oxygen? Well, it's not really relevant for the thigh, because the thighs don't have a lot of oxygen. But it is relevant for the lungs. It is very relevant there. So now you can actually say, "well, let's see what happens" Now that you have high O2, how much CO2 delivery are you getting? And then-- then you can already kind of see it, it's gonna be more, right? because now you got this much, you've got going all the way over here. So this is the new amount of CO2 delivery. And it's gone up. And in fact, you can even show exactly how much it's gone up by-- by simply taking this difference. So, this difference right here, between the two, this is the Haldane Effect. This is the kind of visual way that you can actually see the Haldane Effect. So the Bohr Effect and the Haldane Effect, these are two important strategies our body has, for increasing the amount of O2 delivery and CO2 delivery going back and forth between the lungs and the tissues. ~o0o~