1 00:00:01,371 --> 00:00:04,768 So we've thought a little bit about the lungs and the tissue, 2 00:00:04,768 --> 00:00:07,936 and how there is a kind of (...sing?) relationship between the two, 3 00:00:07,936 --> 00:00:12,726 where they're trying to send little molecules back and forth, 4 00:00:12,726 --> 00:00:17,106 so long it try to send, of course oxygen, out to the tissues, right. 5 00:00:17,106 --> 00:00:22,878 And the tissue is trying to figure out a way to efficiently send back carbondioxide. 6 00:00:22,878 --> 00:00:26,773 So these are the --the kind of core things are going on, between the two. 7 00:00:26,773 --> 00:00:30,458 And remember in turns of getting oxygen accross, there're two major ways we said. 8 00:00:30,458 --> 00:00:34,745 The first one, kind of the easy one, is as dissolved oxygen 9 00:00:34,745 --> 00:00:37,492 --dissolved oxygen in the blood itself. 10 00:00:37,492 --> 00:00:39,506 But that's not the major way. 11 00:00:39,506 --> 00:00:43,282 The major way is when oxygen actually binds hemoglobin --in fact, 12 00:00:43,282 --> 00:00:48,779 we called it HbO2, and the name of that molecule is oxyhemoglobin. 13 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. 14 00:00:53,867 --> 00:00:58,005 And on the other side, coming back from the tissue to the lungs, 15 00:00:58,005 --> 00:01:00,113 you've got dissolved carbondioxide, 16 00:01:00,113 --> 00:01:04,379 little bit of carbondioxide actually literally comes just right in the plasma. 17 00:01:04,379 --> 00:01:08,233 But that's not the majority of how carbondioxide gets back. 18 00:01:08,233 --> 00:01:11,415 The more effective ways of getting carbondioxide back, 19 00:01:11,415 --> 00:01:15,122 remember we have this protonated hemoglobin. 20 00:01:15,122 --> 00:01:18,652 And actually --remember when I-- when I said there's a protonated hemoglobin, 21 00:01:18,652 --> 00:01:22,083 there's gotta be some bicarb floating around in the plasma. 22 00:01:22,083 --> 00:01:24,270 And the reason that that works is because, 23 00:01:24,270 --> 00:01:27,524 when they get back to the lungs, the proton --the bicarb, 24 00:01:27,524 --> 00:01:32,086 actually kind of meet up again, and they form CO2 and water, 25 00:01:32,086 --> 00:01:36,279 and this happens because there's an enzyme called carbonic-anhydrase, 26 00:01:36,279 --> 00:01:37,809 inside of the red blood cells. 27 00:01:37,809 --> 00:01:40,879 So this is where the carbondioxide is actually gets back. 28 00:01:40,879 --> 00:01:44,110 And of course there's the third way, remember there's also some hemoglobin 29 00:01:44,110 --> 00:01:50,386 that actually binds directly to carbondioxide in the process, 30 00:01:50,386 --> 00:01:52,583 you know, it forms a little proton as well, 31 00:01:52,583 --> 00:01:55,947 and that proton can go to this bussiness, right? 32 00:01:55,947 --> 00:01:58,056 It can bind to a hemoglobin as well. 33 00:01:58,056 --> 00:02:02,257 So, there's a little interplay there, but the important ones 34 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 35 00:02:07,486 --> 00:02:12,587 and also in this side, that hemoglobin actually can bind to protons. 36 00:02:12,587 --> 00:02:16,980 Now the fun part about all this is that there's a little competition, right? 37 00:02:16,980 --> 00:02:19,013 A little game going on here. 38 00:02:19,013 --> 00:02:23,443 Because you've got --on the one side you've got hemoglobin binding oxigen, 39 00:02:23,443 --> 00:02:25,817 and let me draw it twice, 40 00:02:25,817 --> 00:02:29,399 and let's say this topple an interaction with proton, 41 00:02:29,399 --> 00:02:34,215 well that proton is gonna wanna snatch away the hemoglobin. 42 00:02:34,215 --> 00:02:36,489 And so there's a little competition for hemoglobin, 43 00:02:36,489 --> 00:02:39,284 and here the oxygen kind of gets left out in the cold, 44 00:02:39,284 --> 00:02:42,679 and the carbondioxide does kind of the same thing we said. We-- 45 00:02:42,679 --> 00:02:48,429 Now we've little hemoglobin bound a carbondioxide and makes a proton in the process, 46 00:02:48,429 --> 00:02:51,885 but again, that leaves oxygen out in the cold. 47 00:02:51,885 --> 00:02:54,614 So depending on whether you have a lot of oxygen around, 48 00:02:54,614 --> 00:02:57,326 if that's the kind of key thing going on, 49 00:02:57,326 --> 00:03:03,448 or whether you have a lot of these kind of products, the proton or the carbondioxide. 50 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, 51 00:03:08,194 --> 00:03:11,185 will determine which way the reaction goes. 52 00:03:11,185 --> 00:03:14,459 So keeping this concept to mind, then I could actually step back and say, well-- 53 00:03:14,459 --> 00:03:19,835 you know, I think that oxygen is affected by carbondioxide and proton, 54 00:03:19,835 --> 00:03:24,733 so I could say, well, these two --carbondioxide and protons, are actually --affecting, 55 00:03:24,733 --> 00:03:29,150 let's say are affecting, 56 00:03:29,243 --> 00:03:33,518 the --let's say, the affinity, 57 00:03:33,579 --> 00:03:41,133 the affinity or the willingness of hemoglobin to bind --of hemoglobin-- four oxygen. 58 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, 59 00:03:45,780 --> 00:03:49,280 and (the repressing?) come along in that they say, well, I think 60 00:03:49,280 --> 00:03:53,182 oxygen actually is affecting, you know, depending on which one 61 00:03:53,182 --> 00:03:55,857 --which perspective you take, you get the oxygen is affecting, 62 00:03:55,857 --> 00:04:03,615 maybe the affinity of hemoglobin for the carbondioxide and proton. 63 00:04:03,754 --> 00:04:08,884 --of hemoglobin for CO2 and protons. 64 00:04:09,392 --> 00:04:12,281 So you could say it from either perspective, 65 00:04:12,281 --> 00:04:16,512 if I wanna point out is that actually in a sense both of these are true, 66 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. 67 00:04:20,628 --> 00:04:24,982 But actually, these're two separate facts, and they have two separate names. 68 00:04:24,982 --> 00:04:28,644 So, the first one, talking about carbondioxide and protons, 69 00:04:28,644 --> 00:04:32,744 their effect is called the {Bohr Effect}. 70 00:04:32,744 --> 00:04:35,448 See, you might see that word, or this description, 71 00:04:35,448 --> 00:04:37,584 This is the Bohr Effect. 72 00:04:37,584 --> 00:04:40,731 And the other one, kind of looking at from the other perspective, 73 00:04:40,731 --> 00:04:44,783 looking at from oxygen perspective, this should be the {Haldane Effect}. 74 00:04:44,783 --> 00:04:47,568 That's just the name of it, Haldane Effect. 75 00:04:47,568 --> 00:04:50,605 So, what is the Bohr Effect and the Haldane effect, 76 00:04:50,605 --> 00:04:54,568 other than simply saying that the things compete for hemoglobin? 77 00:04:54,568 --> 00:04:56,930 Well, let me actually bring up a little bit of the (can?) list, 78 00:04:56,930 --> 00:04:59,159 and let's see if I can diagram this out. 79 00:04:59,159 --> 00:05:02,979 because sometimes I think a little diagram would really go along when explaining these things. 80 00:05:02,979 --> 00:05:05,341 So, let's see if I can do that. 81 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. 82 00:05:09,853 --> 00:05:14,534 This is the partial pressure of oxygen, how much it dissolved in the plasma. 83 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, 84 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. 85 00:05:26,181 --> 00:05:29,746 So what if I slowly increase the partial pressure of oxygen, 86 00:05:29,746 --> 00:05:35,948 see how initially not too much is gonna be binding to the hemoglobin, 87 00:05:35,948 --> 00:05:40,062 but eventually as a few of the molecules bind, you get cooperativity, 88 00:05:40,062 --> 00:05:44,846 and so then slowly the slopes start to rise, becomes more steep. 89 00:05:44,846 --> 00:05:47,541 And this is all because of cooperativity, 90 00:05:47,541 --> 00:05:50,899 oxygen likes to bind where other oxygen have already bound. 91 00:05:50,899 --> 00:05:53,711 And then it's gonna kind of level off. 92 00:05:53,711 --> 00:05:57,322 And the leveling off is because hemoglobin is starting to get saturated. 93 00:05:57,322 --> 00:05:59,755 So there aren't to many extra spots available, 94 00:05:59,755 --> 00:06:02,780 so you need a lot --a lot of oxygen dissolved in the plasma, 95 00:06:02,780 --> 00:06:07,877 to be able to seek out and find those extra remaining spots on hemoglobin. 96 00:06:07,877 --> 00:06:10,171 So let's say we choose two spots. 97 00:06:10,171 --> 00:06:14,777 One spot, let's say, is high amount of oxygen dissolved in the blood, 98 00:06:14,777 --> 00:06:19,000 And this, let's say, is a low amount of oxygen dissolved in the blood. 99 00:06:19,000 --> 00:06:20,986 I'm just kind of choosing them arbitrarily, and don't-- 100 00:06:20,986 --> 00:06:22,515 don't worry about the units. 101 00:06:22,515 --> 00:06:26,020 And if you are to think of where in the body would be high location, 102 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. 103 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, 104 00:06:36,026 --> 00:06:38,443 but not so much oxygen dissolved in the blood. 105 00:06:38,443 --> 00:06:41,142 So these could be two parts of our body, and you-- 106 00:06:41,142 --> 00:06:43,970 you can see that, now if I wanna figure out-- 107 00:06:43,970 --> 00:06:48,643 looking at this curve, how much oxygen is being delivered to the thigh. 108 00:06:48,643 --> 00:06:50,948 Then that's actually pretty easy, I could just say, well, 109 00:06:50,948 --> 00:06:56,544 how much oxygen was there in the lungs --or in the blood vessel leaving the lungs-- 110 00:06:56,544 --> 00:07:00,316 And there's this much oxygen in the blood vessels leaving the lungs. 111 00:07:00,316 --> 00:07:05,418 And there's this much oxygen in the blood vessel leaving the thigh. 112 00:07:05,418 --> 00:07:11,937 So the difference wherever oxygen is between this two points, 113 00:07:11,937 --> 00:07:14,324 that's the amount of oxygen that I got delivered. 114 00:07:14,324 --> 00:07:18,047 So if you want to figure out how much oxygen got delivered to any --any tissue, 115 00:07:18,047 --> 00:07:21,346 you can simply substract these two values. 116 00:07:21,346 --> 00:07:23,049 So that's the oxygen delivery. 117 00:07:23,049 --> 00:07:25,793 But looking at this you can see a kind of interesting point, 118 00:07:25,793 --> 00:07:29,081 which is that if you want it to increase the oxygen delivery, 119 00:07:29,081 --> 00:07:33,087 let's say you want it, for some reason, to increase it, become more efficient, 120 00:07:33,087 --> 00:07:37,667 then really the only way to do that is to have the thigh 121 00:07:37,667 --> 00:07:42,846 kind of become more hypoxic, as he moves to the left on here, 122 00:07:42,846 --> 00:07:46,786 that's really becoming hypoxic, or having less oxygen. 123 00:07:46,786 --> 00:07:53,059 So if he becomes more hypoxic, then yes --you'll, you'll have, you know, 124 00:07:53,059 --> 00:07:56,073 maybe, a lower point here, maybe a point like this, 125 00:07:56,073 --> 00:07:58,894 and that would mean a larger oxygen delivery. 126 00:07:58,894 --> 00:08:02,914 But that's not ideal, you know, when your thighs to become hypoxic, 127 00:08:02,914 --> 00:08:05,391 you know that --that could start aching and hurting. 128 00:08:05,391 --> 00:08:09,649 so is there an another way to have a large oxygen delivery 129 00:08:09,649 --> 00:08:14,935 without having any hypoxic tissue, or tissue that has a low amount of oxygen in it? 130 00:08:14,935 --> 00:08:17,421 And this is where the Bohr Effect comes into play. 131 00:08:17,421 --> 00:08:24,679 So, remember that Bohr Effect is that CO2 and proton affect the hemoglobin affinity for oxygen. 132 00:08:24,679 --> 00:08:29,547 So let's think of a situation --I'll do it in green, 133 00:08:29,547 --> 00:08:32,893 and in this situation we have a lot of carbondioxide and proton, 134 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. 135 00:08:37,421 --> 00:08:39,371 So if I was to sketch another curve, 136 00:08:39,371 --> 00:08:45,656 initially, it's gonna be even less impressive, with less oxygen bound to hemoglobin. 137 00:08:45,656 --> 00:08:50,208 And eventually, once the --once the concentration of oxygen rises enough, 138 00:08:50,208 --> 00:08:54,687 it will start going up up up, and it does bind hemoglobin eventually, 139 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, 140 00:08:59,111 --> 00:09:00,911 but it takes longer. 141 00:09:00,911 --> 00:09:04,111 and so the entire curve looks shifted over. 142 00:09:04,111 --> 00:09:08,957 This-- these conditions of kind of high CO2 and high proton, 143 00:09:08,957 --> 00:09:11,452 that's not really relevant to the lungs. 144 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". 145 00:09:15,305 --> 00:09:18,725 But for the thigh, it is relevant. 146 00:09:18,725 --> 00:09:22,282 Because the thigh has a lot of CO2 and the thigh has a lot of proton. 147 00:09:22,282 --> 00:09:25,812 Again, remember, high protons means low pH. 148 00:09:25,812 --> 00:09:28,114 So, you can think it either way. 149 00:09:28,114 --> 00:09:32,845 So in the thigh, you're gonna get, then, a different point. 150 00:09:32,845 --> 00:09:35,643 Right, it's gonna be on the green curve, not the blue curve. 151 00:09:35,643 --> 00:09:41,111 So, we can draw it at the same O2 level, actually being down here. 152 00:09:41,111 --> 00:09:45,113 So what is the O2 content in the blood that's leaving the thigh? 153 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. 154 00:09:49,321 --> 00:09:55,947 This is the actual amount. And so O2 delivery is actually much more impressive. 155 00:09:55,947 --> 00:10:00,943 Look at that. So O2 delivery is inceased because of the Bohr Effect. 156 00:10:00,943 --> 00:10:02,996 And if you want to know exactly how much it increase, 157 00:10:02,996 --> 00:10:08,132 I could even show you, I could say, well this amount from here down to here, 158 00:10:08,132 --> 00:10:12,278 literally the vertical distance between the green and the blue lines, 159 00:10:12,278 --> 00:10:17,612 so this is the extra oxygen delivered because of the Bohr Effect. 160 00:10:17,612 --> 00:10:21,791 So this is how the Bohr Effect is so important 161 00:10:21,791 --> 00:10:24,206 and actually helping us deliver oxygen to our tissues. 162 00:10:24,206 --> 00:10:26,990 So let's do the same thing now, 163 00:10:26,990 --> 00:10:28,924 but for the Haldane Effect, and to do this, 164 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. 165 00:10:33,661 --> 00:10:36,655 So we're gonna have the amount of carbondioxide there, 166 00:10:36,655 --> 00:10:40,016 and here we'll do carbondioxide content in the blood. 167 00:10:40,016 --> 00:10:43,044 So let's think through this kind of carefully. 168 00:10:43,044 --> 00:10:48,585 Let's first start out with increasing the amount of carbondioxide slowly but surely, 169 00:10:48,585 --> 00:10:49,680 and see that the content goes up. 170 00:10:49,680 --> 00:10:53,379 and here, as you increase the amount of carbondioxide, 171 00:10:53,379 --> 00:10:56,154 the content just kind of goes up as the straight line. 172 00:10:56,154 --> 00:10:59,313 And the reason it doesn't take that S-shape that we had with the oxygen, 173 00:10:59,313 --> 00:11:02,647 is that there is no cooperativity in binding the hemoglobin. 174 00:11:02,647 --> 00:11:04,543 It just kind of goes up straight. 175 00:11:04,543 --> 00:11:06,496 So that's easy enough. 176 00:11:06,496 --> 00:11:09,710 Now let's take two points like we did before. 177 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, 178 00:11:15,119 --> 00:11:17,040 and this'll be a low amount of CO2 in the blood. 179 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? 180 00:11:21,800 --> 00:11:24,704 Well, low CO2, that sounds like the lungs, 181 00:11:24,704 --> 00:11:27,748 there is not too much CO2 there. 182 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? 183 00:11:34,537 --> 00:11:38,867 So the thigh has a high amount, and the lungs have a low amount. 184 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 -- 185 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. 186 00:11:50,939 --> 00:11:53,700 And this is the amount of CO2 in the blood when it goes to the lungs. 187 00:11:53,700 --> 00:11:59,579 So, the amount of CO2 that was delivered from the thigh to the lungs, 188 00:11:59,579 --> 00:12:05,022 is the difference --and so this is how much CO2 delivery were actually getting. 189 00:12:05,022 --> 00:12:09,345 So just like we had O2 delivery, we have this much CO2 delivery. 190 00:12:09,345 --> 00:12:14,512 Now, read over the Haldane Effect, and let's see if we can actually sketch out 191 00:12:14,512 --> 00:12:19,714 another line in the presence of high oxygen, what's gonna happen? 192 00:12:19,714 --> 00:12:22,380 Well, if there is a lot of oxygen around, 193 00:12:22,380 --> 00:12:27,858 then it's gonna change the affinity of hemoblobin for carbondioxide and protons. 194 00:12:27,858 --> 00:12:36,323 So it's gonna low less binding of protons and carbondioxide directly to the hemoglobin. 195 00:12:36,323 --> 00:12:39,279 And that means that you're gonna have less CO2 content, 196 00:12:39,279 --> 00:12:43,251 for any given amount of dissolved CO2 in the blood. 197 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. 198 00:12:49,277 --> 00:12:52,555 So where is this relevant? 199 00:12:52,555 --> 00:12:54,110 Where do you have a lot of oxygen? 200 00:12:54,110 --> 00:12:56,443 Well, it's not really relevant for the thigh, 201 00:12:56,443 --> 00:12:58,516 because the thighs don't have a lot of oxygen. 202 00:12:58,516 --> 00:13:01,068 But it is relevant for the lungs. 203 00:13:01,068 --> 00:13:03,201 It is very relevant there. 204 00:13:03,201 --> 00:13:06,536 So now you can actually say, "well, let's see what happens" 205 00:13:06,536 --> 00:13:11,516 Now that you have high O2, how much CO2 delivery are you getting? 206 00:13:11,516 --> 00:13:14,732 And then-- then you can already kind of see it, it's gonna be more, right? 207 00:13:14,732 --> 00:13:20,468 because now you got this much, you've got going all the way over here. 208 00:13:20,468 --> 00:13:23,232 So this is the new amount of CO2 delivery. 209 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-- 210 00:13:27,866 --> 00:13:31,335 by simply taking this difference. So, this difference right here, 211 00:13:31,335 --> 00:13:35,598 between the two, this is the Haldane Effect. 212 00:13:35,598 --> 00:13:39,859 This is the kind of visual way that you can actually see the Haldane Effect. 213 00:13:39,859 --> 00:13:45,907 So the Bohr Effect and the Haldane Effect, these are two important strategies our body has, 214 00:13:45,907 --> 00:13:49,802 for increasing the amount of O2 delivery and CO2 delivery 215 00:13:49,802 --> 00:13:52,008 going back and forth between the lungs and the tissues. 216 00:13:52,008 --> 99:59:59,999 ~o0o~