1 00:00:01,913 --> 00:00:08,080 Let's talk about exactly how oxygen and carbon dioxide come into and out of the lung. 2 00:00:08,080 --> 00:00:18,663 So you know this is our alveolus in the lungs. This is the last little chamber of air where the lungs are going to interface with blood vessels. 3 00:00:18,663 --> 00:00:26,332 So this is our blood vessel down here. Oxygen is going to make its way from this alveolus into the blood vessel. 4 00:00:26,332 --> 00:00:32,684 It's going to from from the blood vessel into a little red blood cell. This is my red blood cell here. 5 00:00:32,684 --> 00:00:43,219 He is headed out for the first delivery of oxygen that day, and he is going to pick up some oxygen, and it's going to get inside the red blood cell through diffusion. 6 00:00:43,219 --> 00:00:44,681 That's how it gets inside. 7 00:00:44,681 --> 00:00:47,932 So the oxygen has made its way into the red blood cell, and where do you think it goes first? 8 00:00:47,932 --> 00:00:53,377 Well, this red blood cell, sometimes we think of it as a bag of hemoglobin. 9 00:00:53,377 --> 00:00:58,013 Its got millions and millions of hemoglobin proteins. 10 00:00:58,013 --> 00:01:04,030 So this is our hemoglobin protein. It's got four parts to it. Each part can bind an oxygen. 11 00:01:04,030 --> 00:01:14,819 So hemoglobin I can shorten to Hb. Now oxygen is going to bump into, quite literally bump into one of these hemoglobins, and it is going to bind right here. 12 00:01:14,819 --> 00:01:21,928 Initially it is kind of tricky because oxygen doesn't feel very comfortable sitting on the hemoglobin or binding to the hemoglobin. 13 00:01:21,928 --> 00:01:26,927 But once a single oxygen is bound, a second one will come and bind as well. 14 00:01:26,927 --> 00:01:36,334 And then a third will find it much easier, because what is happening is as each oxygen binds it actually changes the conformation or shape of hemoglobin. 15 00:01:36,334 --> 00:01:42,187 So each subsequent oxygen has an easier time binding. We call that cooperativity. 16 00:01:42,187 --> 00:01:45,444 It has the word almost like cooperation in it. 17 00:01:45,444 --> 00:01:53,936 An easy way to think of cooperativity, or the way I think of it, is that if you are at a dinner party you are much more likely to sit where two or three of your friends are already sitting. 18 00:01:53,936 --> 00:02:00,351 If you think of this as a table with four chairs. Rather than sitting at a table by yourself, being the first one to sit there. 19 00:02:00,351 --> 00:02:10,345 So we like sitting with our friends, and oxygen is kind of a friendly molecule, so it also likes to sit where or bind where other oxygens have already bound. 20 00:02:10,345 --> 00:02:18,233 What are the two major ways, based on this diagram how I have drawn it, what are the two major ways that oxygen is going to be transported in the blood. 21 00:02:18,233 --> 00:02:26,245 One is hemoglobin binding oxygen. We call that HbO2. Hb for hemoglobin. O2 for oxygen. 22 00:02:26,245 --> 00:02:33,281 And this molecule, or this enzyme, then is not really called hemoglobin any more. Technically it's called oxyhemoglobin. 23 00:02:33,281 --> 00:02:35,261 That's the name for it. 24 00:02:35,261 --> 00:02:47,216 And another way that you can actually transport oxygen around is that some of this oxygen, I actually underlined it there, is dissolved O2 in plasma. 25 00:02:47,216 --> 00:02:52,934 So some of the oxygen actually just gets dissolved right into the plasma, and that is how it gets moved around. 26 00:02:52,934 --> 00:02:59,511 Now the majority, the vast majority, is actually going to be moved through binding to hemoglobin. 27 00:02:59,511 --> 00:03:03,164 So just a little bit is dissolved in plasma. The majority is bound to hemoglobin. 28 00:03:03,164 --> 00:03:08,349 So this red blood cell goes off to do its delivery. Let's say it's delivering some oxygen out here. 29 00:03:08,349 --> 00:03:13,344 And there is a tissue cell. Now of course there is no way to know where it is going to go that day. 30 00:03:13,344 --> 00:03:25,371 But it's going to go wherever its blood flow takes it. So let's say it takes it up a path over to this thigh cell over in let's say your upper thigh. 31 00:03:25,371 --> 00:03:34,724 So this thigh cell has been making CO2. Remember sometimes we think of CO2 as being made only when the muscle has been working. 32 00:03:34,724 --> 00:03:42,755 But you could be napping, you could be doing whatever, and this CO2 is still being made because cellular respiration is always happening. 33 00:03:42,755 --> 00:03:49,703 So this red blood cell has moved into the capillary right by this thigh cell. 34 00:03:49,703 --> 00:03:58,068 So you've got a situation like this where some of the CO2 is going to diffuse into the red blood cell like that. 35 00:03:58,068 --> 00:04:08,368 What happens once it gets done there? Let me now draw a large version of the red blood cell so you get a closer view of what's going on. 36 00:04:08,368 --> 00:04:14,220 We are in the thigh. The two big conditions in the thigh we have to keep in mind. 37 00:04:14,220 --> 00:04:21,875 One is that you have a high amount of CO2, or a high partial pressure of CO2. This is dissolved in the blood. 38 00:04:21,875 --> 00:04:27,270 The other is that you have a low amount of oxygen. Not too much oxygen in those tissues. 39 00:04:27,270 --> 00:04:29,220 So let's focus on that second point. 40 00:04:29,220 --> 00:04:43,258 If there's not too much oxygen in the tissues, and we know that the hemoglobin is constantly bumping into oxygen molecules and binding them, and they fall off and new ones bind, so it's a dynamic process, 41 00:04:43,258 --> 00:04:52,586 now when there's not too much oxygen around these oxygen molecules are going to fall off as they always do in a dynamic situation. 42 00:04:52,586 --> 00:05:03,639 Except new ones are not going to bind because there is so little oxygen around in the area that less and less oxygen is free and available to bump into hemoglobin and bind to it. 43 00:05:03,639 --> 00:05:10,938 So you are literally going to start getting some oxygen that falls off the hemoglobin simply because the partial pressure of oxygen is low. 44 00:05:10,938 --> 00:05:17,740 So one reason for oxygen to come into the cells is going to be a low PO2. That is one reason. 45 00:05:17,740 --> 00:05:26,417 So these are reasons, and I'm going to give you another one that is why I'm writing reasons, for O2 delivery. 46 00:05:26,417 --> 00:05:31,008 So one of them is going to be simply not having too much oxygen in that area. 47 00:05:31,008 --> 00:05:34,335 A second reason has to do with CO2 itself. 48 00:05:34,335 --> 00:05:39,375 So let's actually follow what happens once CO2 starts getting into the red blood cell. 49 00:05:39,375 --> 00:05:49,025 Now this first CO2 molecule, it's going to meet up with water. Remember there is a lot of water in the red blood cell, and in fact there is water all over the blood. 50 00:05:49,025 --> 00:05:51,359 In fact it is made of mostly water. 51 00:05:51,359 --> 00:05:55,789 So it's not too hard to imagine that a water molecule might bump into this CO2. 52 00:05:55,789 --> 00:06:06,787 Their is an enzyme called carbonic anhydrase. What it does is combines the water and CO2 into what we call H2CO3, or carbonic acid. 53 00:06:06,787 --> 00:06:10,940 Now if it's an acid, try to keep in mind what acids do. 54 00:06:10,940 --> 00:06:14,933 Acids are going to kick off a proton. 55 00:06:14,933 --> 00:06:20,237 So this becomes HC03- and it kicks off a proton. 56 00:06:20,237 --> 00:06:27,977 Notice that now you've got bicarb and a proton on this side, and this bicarb is going to make it's way outside. 57 00:06:27,977 --> 00:06:37,909 So the bicarb goes outside the cell. And the proton, what it does, is it meets up with one of these oxyhemoglobins. 58 00:06:37,909 --> 00:06:48,318 It finds an oxyhemoglobin, remember there are millions of the around, and it literally binds to hemoglobin and it boots off the oxygen 59 00:06:48,318 --> 00:06:52,039 So it binds to hemoglobin, and oxygen falls away. 60 00:06:52,039 --> 00:06:59,256 So this is interesting because this is a second reason for why oxygen gets delivered to the tissues. 61 00:06:59,256 --> 00:07:15,193 And that is that protons compete with oxygen for binding with hemoglobin. So they are competing for hemoglobin. 62 00:07:15,193 --> 00:07:18,909 Now I said there is another thing that happens to carbon dioxide. So what is the other thing. 63 00:07:18,909 --> 00:07:26,089 It turns out that carbon dioxide actually sometimes independently seeks out oxyhemoglobin. Remember there are millions of them. 64 00:07:26,089 --> 00:07:29,371 So it will find one, and it will do the same thing. 65 00:07:29,371 --> 00:07:36,672 It will say, "well, hey hemoglobin, why don't you just come bind with me and get rid of that oxygen." 66 00:07:36,672 --> 00:07:39,435 So it also competes with oxygen. 67 00:07:39,435 --> 00:07:50,440 So you've got some competition with protons, some competition with carbon dioxide, and when carbon dioxide actually binds, an interesting thing is that it makes a proton. 68 00:07:50,440 --> 00:07:55,222 So guess what happens. That proton can go and compete again by itself. 69 00:07:55,222 --> 00:08:00,020 It can compete with oxyhemoglobin and try to kick off another oxygen. 70 00:08:00,020 --> 00:08:07,087 So this system is really interesting because now you've got a few reasons why you have oxygen delivery. 71 00:08:07,087 --> 00:08:18,156 You've got protons competing, you've got CO2 competing with oxygen, so you've got a couple of sources of competition. 72 00:08:18,156 --> 00:08:22,810 And you've got of course simply the fact that there is just not too much oxygen around. 73 00:08:22,810 --> 00:08:25,511 So these are reasons for oxygen delivery. 74 00:08:25,511 --> 00:08:35,770 So at this point you've got oxygen that is delivered to the cells. And these hemoglobin molecules are still in our cell of course, inside of our red blood cell. 75 00:08:35,770 --> 00:08:40,556 And these hemoglobin molecules have now been bound by different things. 76 00:08:40,556 --> 00:08:44,325 So they are no longer bound by oxygen, so you can't really call them oxyhemoglobin anymore. 77 00:08:44,325 --> 00:08:57,893 Instead they have protons on them like this, and they might have some COO- on them. Actually let me do that in the original orange color. 78 00:08:57,893 --> 00:09:01,903 So they basically have different things binding to them. 79 00:09:01,903 --> 00:09:07,708 And as a result the oxygen is now gone and our system so far looks good. 80 00:09:07,708 --> 00:09:17,075 But, let me now turn it around, and let's ask the question, "How do we carry carbon dioxide from the thigh back to the lung?" 81 00:09:17,075 --> 00:09:23,641 Let me start out by replacing the word thigh with lung. So now are blood has traveled back to the lung. 82 00:09:23,641 --> 00:09:30,392 The question is how much carbon dioxide did it bring with it? And in what different forms did that carbon dioxide come. 83 00:09:30,392 --> 00:09:38,474 So we've got a couple of situations. We've got a high amount of oxygen here and we've got a low amount of CO2. 84 00:09:38,474 --> 00:09:41,990 So it is really quite different from what was happening in the thigh. 85 00:09:41,990 --> 00:09:46,869 So when the blood is leaving the thigh headed back to the lung, what does it have with it? 86 00:09:46,869 --> 00:09:59,593 Well its got a few things. One is that it has got hemoglobin that is bound to carbon dioxide, and this is called carbaminohemoglobin. 87 00:09:59,593 --> 00:10:07,991 And then it has also got some protons that are bound to hemoglobin. So the protons themselves are attached to hemoglobin. 88 00:10:07,991 --> 00:10:18,910 And just keep in mind that for every proton that is attached to hemoglobin you have also got a bicarb dissolved in the plasma. Because it is a one to one ratio of these things. 89 00:10:18,910 --> 00:10:24,188 You've got a bunch of bicarb in the plasma as well. I'm writing in parentheses just so we don't forget that point. 90 00:10:24,188 --> 00:10:26,328 And finally what else is in the blood. 91 00:10:26,328 --> 00:10:30,971 We've got some CO2 that just gets dissolved right into the plasma. 92 00:10:30,971 --> 00:10:36,807 So this is sounding a little bit like what happened in the oxygen situation where you had some CO2 in the plasma itself. 93 00:10:36,807 --> 00:10:41,254 And this is what is headed back from the thigh to the lung. 94 00:10:41,254 --> 00:10:45,010 So now in the lung what happens. You've got all this stuff with you. 95 00:10:45,010 --> 00:10:54,689 The first thing that happens is that you've got a lot of oxygen in the area. A lot of oxygen in the tissue of the lung. 96 00:10:54,689 --> 00:10:58,810 It diffuses into the cell. Goes into the cell. 97 00:10:58,810 --> 00:11:06,041 The oxygen, because there is so much of it, is going to go try to sit in these hemoglobins. 98 00:11:06,041 --> 00:11:08,195 It is going to try and find its spot. 99 00:11:08,195 --> 00:11:12,894 And if it does, what it does in terms of the equations is the reverse of what happened before. 100 00:11:12,894 --> 00:11:23,045 Now you've got a lot of oxygen here, you've got a lot of oxygen here, and because these are reversible reactions, you basically push this entire reaction to the left. 101 00:11:23,045 --> 00:11:29,625 So now you've got a lot of oxygen, and it basically competes for that hemoglobin again. 102 00:11:29,625 --> 00:11:33,792 So remember before the protons actually ended up snatching hemoglobin away from oxygen. 103 00:11:33,792 --> 00:11:39,690 And now oxygen returns the favor. It says, "Well I'm going to snatch that hemoglobin right back." 104 00:11:39,690 --> 00:11:47,240 You've got this proton that is left out by itself, and on this side you've got this CO2 that is left out by itself. 105 00:11:47,240 --> 00:11:53,108 So a couple of interesting things are happening. Let me make sure I keep track of them up here. 106 00:11:53,108 --> 00:12:04,339 So what are some reasons now for CO2 delivery. How is it getting delivered back to the lungs? 107 00:12:04,339 --> 00:12:10,889 The first one, the most obvious one, is that we said the lungs have low CO2 content. 108 00:12:10,889 --> 00:12:18,307 Simply having very low CO2 around means that whatever is there is going to diffuse into the alveolus. 109 00:12:18,307 --> 00:12:24,541 Whatever is in that red blood cell is going to diffuse in here simply because there is not a lot of CO2 around. 110 00:12:24,541 --> 00:12:28,711 So instead of diffusing into the red blood cell, now it is going to want to diffuse out. 111 00:12:28,711 --> 00:12:42,526 A second reason, though this is the more interesting reason, is that you actually have oxygen competing, oxygen competes with, protons and CO2. 112 00:12:42,526 --> 00:12:46,003 So it's competing with protons and CO2 for hemoglobin. 113 00:12:46,003 --> 00:12:48,841 And that is what we drew in our equation down there. 114 00:12:48,841 --> 00:12:53,421 So what it does is basically get you back to the oxyhemoglobin. 115 00:12:53,421 --> 00:12:58,106 That is the first thing, and that is what we have already drawn there. We've draw oxygen bound to hemoglobin. 116 00:12:58,106 --> 00:13:11,376 It means that these little CO2's fall off, these little protons fall off, and they are back in the inside of the cell. 117 00:13:11,376 --> 00:13:15,854 So if you are CO2 you can again just diffuse into the alveolus. 118 00:13:15,854 --> 00:13:22,521 But if you are a proton, let's say you are a proton and you just fell off of the hemoglobin because it got snatched away by oxygen. 119 00:13:22,521 --> 00:13:35,765 Well then this little bicarb is going to come back inside and it combines with the proton, and these two form, you guessed it, H2CO3. 120 00:13:35,765 --> 00:13:40,173 So remember this is reversible as well. So they go back and form H2CO3. 121 00:13:40,173 --> 00:13:47,425 And it turns out that you can go from H2CO3 over here also using carbonic anydrase. 122 00:13:47,425 --> 00:13:54,489 So you basically just do this whole reaction backwards, and now you can see that you have got more CO2 formed. 123 00:13:54,489 --> 00:14:01,963 So by having bicarb dissolved in the plasma, it is just staying there and waiting it out. 124 00:14:01,963 --> 00:14:09,028 And as soon as those protons are bumped off of the hemoglobin, they go and combine with them and form the CO2. 125 00:14:09,028 --> 00:14:22,079 So you've got CO2 coming from the bicarb, CO2 coming from the carbamino hemoglobin, and you've also got the CO2 that had dissolved in the plasma. 126 00:14:22,079 --> 00:14:25,462 So three different ways that CO2 is actually coming back. 127 00:14:25,462 --> 00:14:37,048 Once all that CO2 is in the lungs, it is going to diffuse right into the alveolus because the amount of CO2 is so darn low that the diffusion gradient gets it going toward the alveolus. 128 00:14:37,048 --> 00:14:45,491 And of these different strategies, the most important one that gets us most of our carbon dioxide transportation, is this one, this middle one, 129 00:14:45,491 --> 00:14:50,441 where the protons are actually binding hemoglobin and all that bicarbonate is dissolved in plasma. 130 00:14:50,441 --> 00:14:54,441 So of the three different ways that carbon dioxide comes back, that is the one you should pay most particular attention to.