WEBVTT 00:00:01.371 --> 00:00:04.768 So we've thought a little bit about the lungs and the tissue, 00:00:04.768 --> 00:00:07.936 and how there is a kind of (...sing?) relationship between the two, 00:00:07.936 --> 00:00:12.726 where they're trying to send little molecules back and forth, 00:00:12.726 --> 00:00:17.106 so long it try to send, of course oxygen, out to the tissues, right. 00:00:17.106 --> 00:00:22.878 And the tissue is trying to figure out a way to efficiently send back carbondioxide. 00:00:22.878 --> 00:00:26.773 So these are the --the kind of core things are going on, between the two. 00:00:26.773 --> 00:00:30.458 And remember in turns of getting oxygen accross, there're two major ways we said. 00:00:30.458 --> 00:00:34.745 The first one, kind of the easy one, is as dissolved oxygen 00:00:34.745 --> 00:00:37.492 --dissolved oxygen in the blood itself. 00:00:37.492 --> 00:00:39.506 But that's not the major way. 00:00:39.506 --> 00:00:43.282 The major way is when oxygen actually binds hemoglobin --in fact, 00:00:43.282 --> 00:00:48.779 we called it HbO2, and the name of that molecule is oxyhemoglobin. 00:00:48.779 --> 00:00:53.867 So this is kind of how the majority of the oxygen is gonna get delivered to the tissues. 00:00:53.867 --> 00:00:58.005 And on the other side, coming back from the tissue to the lungs, 00:00:58.005 --> 00:01:00.113 you've got dissolved carbondioxide, 00:01:00.113 --> 00:01:04.379 little bit of carbondioxide actually literally comes just right in the plasma. 00:01:04.379 --> 00:01:08.233 But that's not the majority of how carbondioxide gets back. 00:01:08.233 --> 00:01:11.415 The more effective ways of getting carbondioxide back, 00:01:11.415 --> 00:01:15.122 remember we have this protonated hemoglobin. 00:01:15.122 --> 00:01:18.652 And actually --remember when I-- when I said there's a protonated hemoglobin, 00:01:18.652 --> 00:01:22.083 there's gotta be some bicarb floating around in the plasma. 00:01:22.083 --> 00:01:24.270 And the reason that that works is because, 00:01:24.270 --> 00:01:27.524 when they get back to the lungs, the proton --the bicarb, 00:01:27.524 --> 00:01:32.086 actually kind of meet up again, and they form CO2 and water, 00:01:32.086 --> 00:01:36.279 and this happens because there's an enzyme called carbonic-anhydrase, 00:01:36.279 --> 00:01:37.809 inside of the red blood cells. 00:01:37.809 --> 00:01:40.879 So this is where the carbondioxide is actually gets back. 00:01:40.879 --> 00:01:44.110 And of course there's the third way, remember there's also some hemoglobin 00:01:44.110 --> 00:01:50.386 that actually binds directly to carbondioxide in the process, 00:01:50.386 --> 00:01:52.583 you know, it forms a little proton as well, 00:01:52.583 --> 00:01:55.947 and that proton can go to this bussiness, right? 00:01:55.947 --> 00:01:58.056 It can bind to a hemoglobin as well. 00:01:58.056 --> 00:02:02.257 So, there's a little interplay there, but the important ones 00:02:02.257 --> 00:02:07.486 I want to really kind of focus in on, are the fact that hemoglobin can bind to oxygen 00:02:07.486 --> 00:02:12.587 and also in this side, that hemoglobin actually can bind to protons. 00:02:12.587 --> 00:02:16.980 Now the fun part about all this is that there's a little competition, right? 00:02:16.980 --> 00:02:19.013 A little game going on here. 00:02:19.013 --> 00:02:23.443 Because you've got --on the one side you've got hemoglobin binding oxigen, 00:02:23.443 --> 00:02:25.817 and let me draw it twice, 00:02:25.817 --> 00:02:29.399 and let's say this topple an interaction with proton, 00:02:29.399 --> 00:02:34.215 well that proton is gonna wanna snatch away the hemoglobin. 00:02:34.215 --> 00:02:36.489 And so there's a little competition for hemoglobin, 00:02:36.489 --> 00:02:39.284 and here the oxygen kind of gets left out in the cold, 00:02:39.284 --> 00:02:42.679 and the carbondioxide does kind of the same thing we said. We-- 00:02:42.679 --> 00:02:48.429 Now we've little hemoglobin bound a carbondioxide and makes a proton in the process, 00:02:48.429 --> 00:02:51.885 but again, that leaves oxygen out in the cold. 00:02:51.885 --> 00:02:54.614 So depending on whether you have a lot of oxygen around, 00:02:54.614 --> 00:02:57.326 if that's the kind of key thing going on, 00:02:57.326 --> 00:03:03.448 or whether you have a lot of these kind of products, the proton or the carbondioxide. 00:03:03.448 --> 00:03:08.194 Depending on which one you have more of, floating around in the --in the tissue, in the cell, 00:03:08.194 --> 00:03:11.185 will determine which way the reaction goes. 00:03:11.185 --> 00:03:14.459 So keeping this concept to mind, then I could actually step back and say, well-- 00:03:14.459 --> 00:03:19.835 you know, I think that oxygen is affected by carbondioxide and proton, 00:03:19.835 --> 00:03:24.733 so I could say, well, these two --carbondioxide and protons, are actually --affecting, 00:03:24.733 --> 00:03:29.150 let's say are affecting, 00:03:29.243 --> 00:03:33.518 the --let's say, the affinity, 00:03:33.579 --> 00:03:41.133 the affinity or the willingness of hemoglobin to bind --of hemoglobin-- four oxygen. 00:03:41.133 --> 00:03:45.780 Right, that's one kind of statement you could make by looking at that kind of competition, 00:03:45.780 --> 00:03:49.280 and (the repressing?) come along in that they say, well, I think 00:03:49.280 --> 00:03:53.182 oxygen actually is affecting, you know, depending on which one 00:03:53.182 --> 00:03:55.857 --which perspective you take, you get the oxygen is affecting, 00:03:55.857 --> 00:04:03.615 maybe the affinity of hemoglobin for the carbondioxide and proton. 00:04:03.754 --> 00:04:08.884 --of hemoglobin for CO2 and protons. 00:04:09.392 --> 00:04:12.281 So you could say it from either perspective, 00:04:12.281 --> 00:04:16.512 if I wanna point out is that actually in a sense both of these are true, 00:04:16.512 --> 00:04:20.628 In a lot of times we think, well, maybe it's just saying the same thing twice. 00:04:20.628 --> 00:04:24.982 But actually, these're two separate facts, and they have two separate names. 00:04:24.982 --> 00:04:28.644 So, the first one, talking about carbondioxide and protons, 00:04:28.644 --> 00:04:32.744 their effect is called the {Bohr Effect}. 00:04:32.744 --> 00:04:35.448 See, you might see that word, or this description, 00:04:35.448 --> 00:04:37.584 This is the Bohr Effect. 00:04:37.584 --> 00:04:40.731 And the other one, kind of looking at from the other perspective, 00:04:40.731 --> 00:04:44.783 looking at from oxygen perspective, this should be the {Haldane Effect}. 00:04:44.783 --> 00:04:47.568 That's just the name of it, Haldane Effect. 00:04:47.568 --> 00:04:50.605 So, what is the Bohr Effect and the Haldane effect, 00:04:50.605 --> 00:04:54.568 other than simply saying that the things compete for hemoglobin? 00:04:54.568 --> 00:04:56.930 Well, let me actually bring up a little bit of the (can?) list, 00:04:56.930 --> 00:04:59.159 and let's see if I can diagram this out. 00:04:59.159 --> 00:05:02.979 because sometimes I think a little diagram would really go along when explaining these things. 00:05:02.979 --> 00:05:05.341 So, let's see if I can do that. 00:05:05.372 --> 00:05:09.853 Let's use a little graph and see if you can illustrate the Bohr Effect on this graph. 00:05:09.853 --> 00:05:14.534 This is the partial pressure of oxygen, how much it dissolved in the plasma. 00:05:14.534 --> 00:05:20.632 And this is oxygen content which is to say how much total oxygen is there in the blood, 00:05:20.632 --> 00:05:26.181 and this of course takes an account mostly the amount of oxygen that's bound to hemoglobin. 00:05:26.181 --> 00:05:29.746 So what if I slowly increase the partial pressure of oxygen, 00:05:29.746 --> 00:05:35.948 see how initially not too much is gonna be binding to the hemoglobin, 00:05:35.948 --> 00:05:40.062 but eventually as a few of the molecules bind, you get cooperativity, 00:05:40.062 --> 00:05:44.846 and so then slowly the slopes start to rise, becomes more steep. 00:05:44.846 --> 00:05:47.541 And this is all because of cooperativity, 00:05:47.541 --> 00:05:50.899 oxygen likes to bind where other oxygen have already bound. 00:05:50.899 --> 00:05:53.711 And then it's gonna kind of level off. 00:05:53.711 --> 00:05:57.322 And the leveling off is because hemoglobin is starting to get saturated. 00:05:57.322 --> 00:05:59.755 So there aren't to many extra spots available, 00:05:59.755 --> 00:06:02.780 so you need a lot --a lot of oxygen dissolved in the plasma, 00:06:02.780 --> 00:06:07.877 to be able to seek out and find those extra remaining spots on hemoglobin. 00:06:07.877 --> 00:06:10.171 So let's say we choose two spots. 00:06:10.171 --> 00:06:14.777 One spot, let's say, is high amount of oxygen dissolved in the blood, 00:06:14.777 --> 00:06:19.000 And this, let's say, is a low amount of oxygen dissolved in the blood. 00:06:19.000 --> 00:06:20.986 I'm just kind of choosing them arbitrarily, and don't-- 00:06:20.986 --> 00:06:22.515 don't worry about the units. 00:06:22.515 --> 00:06:26.020 And if you are to think of where in the body would be high location, 00:06:26.020 --> 00:06:30.121 that could be something like the lungs, where you have a lot of oxygen dissolved in bloods. 00:06:30.121 --> 00:06:36.026 And low would be, let's say, the thigh muscle where there is a lot of CO2, 00:06:36.026 --> 00:06:38.443 but not so much oxygen dissolved in the blood. 00:06:38.443 --> 00:06:41.142 So these could be two parts of our body, and you-- 00:06:41.142 --> 00:06:43.970 you can see that, now if I wanna figure out-- 00:06:43.970 --> 00:06:48.643 looking at this curve, how much oxygen is being delivered to the thigh. 00:06:48.643 --> 00:06:50.948 Then that's actually pretty easy, I could just say, well, 00:06:50.948 --> 00:06:56.544 how much oxygen was there in the lungs --or in the blood vessel leaving the lungs-- 00:06:56.544 --> 00:07:00.316 And there's this much oxygen in the blood vessels leaving the lungs. 00:07:00.316 --> 00:07:05.418 And there's this much oxygen in the blood vessel leaving the thigh. 00:07:05.418 --> 00:07:11.937 So the difference wherever oxygen is between this two points, 00:07:11.937 --> 00:07:14.324 that's the amount of oxygen that I got delivered. 00:07:14.324 --> 00:07:18.047 So if you want to figure out how much oxygen got delivered to any --any tissue, 00:07:18.047 --> 00:07:21.346 you can simply substract these two values. 00:07:21.346 --> 00:07:23.049 So that's the oxygen delivery. 00:07:23.049 --> 00:07:25.793 But looking at this you can see a kind of interesting point, 00:07:25.793 --> 00:07:29.081 which is that if you want it to increase the oxygen delivery, 00:07:29.081 --> 00:07:33.087 let's say you want it, for some reason, to increase it, become more efficient, 00:07:33.087 --> 00:07:37.667 then really the only way to do that is to have the thigh 00:07:37.667 --> 00:07:42.846 kind of become more hypoxic, as he moves to the left on here, 00:07:42.846 --> 00:07:46.786 that's really becoming hypoxic, or having less oxygen. 00:07:46.786 --> 00:07:53.059 So if he becomes more hypoxic, then yes --you'll, you'll have, you know, 00:07:53.059 --> 00:07:56.073 maybe, a lower point here, maybe a point like this, 00:07:56.073 --> 00:07:58.894 and that would mean a larger oxygen delivery. 00:07:58.894 --> 00:08:02.914 But that's not ideal, you know, when your thighs to become hypoxic, 00:08:02.914 --> 00:08:05.391 you know that --that could start aching and hurting. 00:08:05.391 --> 00:08:09.649 so is there an another way to have a large oxygen delivery 00:08:09.649 --> 00:08:14.935 without having any hypoxic tissue, or tissue that has a low amount of oxygen in it? 00:08:14.935 --> 00:08:17.421 And this is where the Bohr Effect comes into play. 00:08:17.421 --> 00:08:24.679 So, remember that Bohr Effect is that CO2 and proton affect the hemoglobin affinity for oxygen. 00:08:24.679 --> 00:08:29.547 So let's think of a situation --I'll do it in green, 00:08:29.547 --> 00:08:32.893 and in this situation we have a lot of carbondioxide and proton, 00:08:32.893 --> 00:08:37.421 the Bohr Effect thought is, that it's kind of a bit harder for oxygen to bind hemoglobin. 00:08:37.421 --> 00:08:39.371 So if I was to sketch another curve, 00:08:39.371 --> 00:08:45.656 initially, it's gonna be even less impressive, with less oxygen bound to hemoglobin. 00:08:45.656 --> 00:08:50.208 And eventually, once the --once the concentration of oxygen rises enough, 00:08:50.208 --> 00:08:54.687 it will start going up up up, and it does bind hemoglobin eventually, 00:08:54.687 --> 00:08:59.111 so it's not like it'll never bind hemoglobin in the presence of carbondioxide and protons, 00:08:59.111 --> 00:09:00.911 but it takes longer. 00:09:00.911 --> 00:09:04.111 and so the entire curve looks shifted over. 00:09:04.111 --> 00:09:08.957 This-- these conditions of kind of high CO2 and high proton, 00:09:08.957 --> 00:09:11.452 that's not really relevant to the lungs. 00:09:11.452 --> 00:09:15.305 The lungs will think you --for us, you know-- "who cares, we don't really have these conditions". 00:09:15.305 --> 00:09:18.725 But for the thigh, it is relevant. 00:09:18.725 --> 00:09:22.282 Because the thigh has a lot of CO2 and the thigh has a lot of proton. 00:09:22.282 --> 00:09:25.812 Again, remember, high protons means low pH. 00:09:25.812 --> 00:09:28.114 So, you can think it either way. 00:09:28.114 --> 00:09:32.845 So in the thigh, you're gonna get, then, a different point. 00:09:32.845 --> 00:09:35.643 Right, it's gonna be on the green curve, not the blue curve. 00:09:35.643 --> 00:09:41.111 So, we can draw it at the same O2 level, actually being down here. 00:09:41.111 --> 00:09:45.113 So what is the O2 content in the blood that's leaving the thigh? 00:09:45.113 --> 00:09:49.321 Well then, to do it properly out, they'll-- you'll be, actually you'll be over here. 00:09:49.321 --> 00:09:55.947 This is the actual amount. And so O2 delivery is actually much more impressive. 00:09:55.947 --> 00:10:00.943 Look at that. So O2 delivery is inceased because of the Bohr Effect. 00:10:00.943 --> 00:10:02.996 And if you want to know exactly how much it increase, 00:10:02.996 --> 00:10:08.132 I could even show you, I could say, well this amount from here down to here, 00:10:08.132 --> 00:10:12.278 literally the vertical distance between the green and the blue lines, 00:10:12.278 --> 00:10:17.612 so this is the extra oxygen delivered because of the Bohr Effect. 00:10:17.612 --> 00:10:21.791 So this is how the Bohr Effect is so important 00:10:21.791 --> 00:10:24.206 and actually helping us deliver oxygen to our tissues. 00:10:24.206 --> 00:10:26.990 So let's do the same thing now, 00:10:26.990 --> 00:10:28.924 but for the Haldane Effect, and to do this, 00:10:28.924 --> 00:10:33.661 we actually have to switch things around, so our units and our axis are gonna be different. 00:10:33.661 --> 00:10:36.655 So we're gonna have the amount of carbondioxide there, 00:10:36.655 --> 00:10:40.016 and here we'll do carbondioxide content in the blood. 00:10:40.016 --> 00:10:43.044 So let's think through this kind of carefully. 00:10:43.044 --> 00:10:48.585 Let's first start out with increasing the amount of carbondioxide slowly but surely, 00:10:48.585 --> 00:10:49.680 and see that the content goes up. 00:10:49.680 --> 00:10:53.379 and here, as you increase the amount of carbondioxide, 00:10:53.379 --> 00:10:56.154 the content just kind of goes up as the straight line. 00:10:56.154 --> 00:10:59.313 And the reason it doesn't take that S-shape that we had with the oxygen, 00:10:59.313 --> 00:11:02.647 is that there is no cooperativity in binding the hemoglobin. 00:11:02.647 --> 00:11:04.543 It just kind of goes up straight. 00:11:04.543 --> 00:11:06.496 So that's easy enough. 00:11:06.496 --> 00:11:09.710 Now let's take two points like we did before. 00:11:09.710 --> 00:11:15.119 Let's take a point --let's say, up here this'll be high amount of CO2 in the blood, 00:11:15.119 --> 00:11:17.040 and this'll be a low amount of CO2 in the blood. 00:11:17.040 --> 00:11:21.800 So you'd have a low amount, let's say right here, in what part of tissue? 00:11:21.800 --> 00:11:24.704 Well, low CO2, that sounds like the lungs, 00:11:24.704 --> 00:11:27.748 there is not too much CO2 there. 00:11:27.748 --> 00:11:34.537 But high CO2 probably is the thighs, 'cause the thigh is like a little CO2 factories, right? 00:11:34.537 --> 00:11:38.867 So the thigh has a high amount, and the lungs have a low amount. 00:11:38.867 --> 00:11:44.046 So, if I wanna look at the amount of CO2 delivered, we do it the same way with -- 00:11:44.046 --> 00:11:50.693 okay, well the thighs had a high amount, this is the amount of CO2 in the blood, remember. 00:11:50.939 --> 00:11:53.700 And this is the amount of CO2 in the blood when it goes to the lungs. 00:11:53.700 --> 00:11:59.579 So, the amount of CO2 that was delivered from the thigh to the lungs, 00:11:59.579 --> 00:12:05.022 is the difference --and so this is how much CO2 delivery were actually getting. 00:12:05.022 --> 00:12:09.345 So just like we had O2 delivery, we have this much CO2 delivery. 00:12:09.345 --> 00:12:14.512 Now, read over the Haldane Effect, and let's see if we can actually sketch out 00:12:14.512 --> 00:12:19.714 another line in the presence of high oxygen, what's gonna happen? 00:12:19.714 --> 00:12:22.380 Well, if there is a lot of oxygen around, 00:12:22.380 --> 00:12:27.858 then it's gonna change the affinity of hemoblobin for carbondioxide and protons. 00:12:27.858 --> 00:12:36.323 So it's gonna low less binding of protons and carbondioxide directly to the hemoglobin. 00:12:36.323 --> 00:12:39.279 And that means that you're gonna have less CO2 content, 00:12:39.279 --> 00:12:43.251 for any given amount of dissolved CO2 in the blood. 00:12:43.251 --> 00:12:49.277 So that line is still a straight line, but it's actually --you notice it's kind of sloped downwards. 00:12:49.277 --> 00:12:52.555 So where is this relevant? 00:12:52.555 --> 00:12:54.110 Where do you have a lot of oxygen? 00:12:54.110 --> 00:12:56.443 Well, it's not really relevant for the thigh, 00:12:56.443 --> 00:12:58.516 because the thighs don't have a lot of oxygen. 00:12:58.516 --> 00:13:01.068 But it is relevant for the lungs. 00:13:01.068 --> 00:13:03.201 It is very relevant there. 00:13:03.201 --> 00:13:06.536 So now you can actually say, "well, let's see what happens" 00:13:06.536 --> 00:13:11.516 Now that you have high O2, how much CO2 delivery are you getting? 00:13:11.516 --> 00:13:14.732 And then-- then you can already kind of see it, it's gonna be more, right? 00:13:14.732 --> 00:13:20.468 because now you got this much, you've got going all the way over here. 00:13:20.468 --> 00:13:23.232 So this is the new amount of CO2 delivery. 00:13:23.232 --> 00:13:27.866 And it's gone up. And in fact, you can even show exactly how much it's gone up by-- 00:13:27.866 --> 00:13:31.335 by simply taking this difference. So, this difference right here, 00:13:31.335 --> 00:13:35.598 between the two, this is the Haldane Effect. 00:13:35.598 --> 00:13:39.859 This is the kind of visual way that you can actually see the Haldane Effect. 00:13:39.859 --> 00:13:45.907 So the Bohr Effect and the Haldane Effect, these are two important strategies our body has, 00:13:45.907 --> 00:13:49.802 for increasing the amount of O2 delivery and CO2 delivery 00:13:49.802 --> 00:13:52.008 going back and forth between the lungs and the tissues. 00:13:52.008 --> 99:59:59.999 ~o0o~