1 00:00:02,071 --> 00:00:04,679 Voiceover: So the two categories that we assign to emphysema, 2 00:00:04,679 --> 00:00:07,398 the centriacinar and the panacinar, 3 00:00:07,398 --> 00:00:09,299 they're basically referring to geography. 4 00:00:09,510 --> 00:00:11,590 It's like saying, my city's flooded, 5 00:00:11,590 --> 00:00:14,534 and is it contained to the central streets, the main street, 6 00:00:14,534 --> 00:00:15,762 or is it everywhere? 7 00:00:16,198 --> 00:00:18,674 So basically, it's asking, "Where is the emphysema?" 8 00:00:19,062 --> 00:00:20,967 So a little Latin review, we have "pan," 9 00:00:20,967 --> 00:00:22,310 which means everywhere, 10 00:00:22,310 --> 00:00:23,906 and "centri," so "center." 11 00:00:24,598 --> 00:00:26,802 Now, what on earth is an "acinar?" 12 00:00:26,950 --> 00:00:29,158 And basically, that's a geographical term too, 13 00:00:29,158 --> 00:00:31,026 and this is an "acinus." 14 00:00:32,071 --> 00:00:34,194 To orient ourselves, let's draw the lungs. 15 00:00:34,310 --> 00:00:37,638 We have the trachea here, and the two big bronchi, 16 00:00:37,638 --> 00:00:40,737 so you have your lobe of lung here, and lobe of lung here. 17 00:00:40,837 --> 00:00:43,637 The bronchi are kind of like your tree trunks, 18 00:00:43,637 --> 00:00:45,973 and as they start to branch off like this, 19 00:00:45,973 --> 00:00:48,998 the smaller airways here are called "bronchioles," 20 00:00:48,998 --> 00:00:51,382 and that's basically the level we're at right here. 21 00:00:51,382 --> 00:00:54,757 Here is our bronchiole, and the rest of this branch 22 00:00:54,757 --> 00:00:57,361 that I've drawn, is just the rest of the airway. 23 00:00:57,493 --> 00:01:00,305 So here, we have our alveoli cluster. 24 00:01:02,182 --> 00:01:04,549 So there are many many countless branches 25 00:01:04,549 --> 00:01:08,428 of acini in the lungs, but this is what one would look like. 26 00:01:08,428 --> 00:01:12,085 So that tells us centriacinar versus panacinar, 27 00:01:12,085 --> 00:01:14,910 we're talking about where, in this, are we? 28 00:01:15,246 --> 00:01:17,213 So in this normal acinus that I've drawn, 29 00:01:17,213 --> 00:01:19,597 you can see the tightly, little coiled structures here 30 00:01:19,597 --> 00:01:22,377 in the alveoli, and along the airways too. 31 00:01:23,150 --> 00:01:25,293 This elastic, coiled shape is possible 32 00:01:25,293 --> 00:01:27,593 because of our protein, elastin. 33 00:01:27,885 --> 00:01:31,085 Elastin is cleaved by elastase, 34 00:01:31,085 --> 00:01:34,413 which is this protein inhibitor, which is good usually, 35 00:01:34,413 --> 00:01:36,205 because we want the tissue to turn over, 36 00:01:36,205 --> 00:01:37,577 old ones to be eaten up. 37 00:01:37,773 --> 00:01:41,821 And this whole system is controlled by Alpha 1-antitrypsin, 38 00:01:41,821 --> 00:01:44,333 which is a compound made in the liver, and it's job 39 00:01:44,333 --> 00:01:46,633 is to regulate the amount of elastase. 40 00:01:47,341 --> 00:01:51,293 So, by inhibiting the elastase, it inhibits the elastin, 41 00:01:51,293 --> 00:01:54,654 the antitrypsin lets there be more elastin. 42 00:01:55,837 --> 00:01:58,717 So whether we're going to have centriacinar here, 43 00:01:58,717 --> 00:02:01,692 or panacinar destruction of elastin, 44 00:02:01,692 --> 00:02:03,356 fully depends on the pathophysiology 45 00:02:03,356 --> 00:02:05,933 of why is there so much elastase? 46 00:02:05,933 --> 00:02:07,560 Why is elastin getting destroyed? 47 00:02:08,781 --> 00:02:10,953 So first, let's take a look at centriacinar. 48 00:02:11,340 --> 00:02:14,636 And this is what it looks like, so I've draw the same acinus 49 00:02:14,636 --> 00:02:15,852 that we have up there, 50 00:02:15,852 --> 00:02:17,679 but because of the lack of elastin in it, 51 00:02:17,679 --> 00:02:19,912 there're fewer of the walls to begin with. 52 00:02:20,028 --> 00:02:22,732 And, whatever walls there are left, it's because 53 00:02:22,732 --> 00:02:24,765 it's so floppy, that's why it looks bigger like that, 54 00:02:24,765 --> 00:02:27,064 it just doesn't hold that nice shape. 55 00:02:27,500 --> 00:02:30,364 So this is what we call "centriacinar distribution," 56 00:02:30,364 --> 00:02:32,251 as you can see, geographically, 57 00:02:32,251 --> 00:02:34,090 it's earlier, it's not everywhere. 58 00:02:34,476 --> 00:02:36,780 Centriacinar is really related to inflammation, 59 00:02:36,780 --> 00:02:40,119 which is the first pathophysiology of emphysema. 60 00:02:40,527 --> 00:02:42,651 Now inflammation recruits neutrophils, 61 00:02:42,651 --> 00:02:44,843 these white blood cells that flight inflammation 62 00:02:44,843 --> 00:02:46,103 everywhere in the body. 63 00:02:46,203 --> 00:02:47,819 But when they get to the lungs, the neutrophils 64 00:02:47,819 --> 00:02:51,480 make elastase, that's the whole culprit here. 65 00:02:51,883 --> 00:02:54,664 So it's too much elastase, from too much inflammation. 66 00:02:54,683 --> 00:02:58,215 And the way we'd get that, most commonly, is from smoking. 67 00:02:59,003 --> 00:03:01,035 So even though, when you see somebody smoking, 68 00:03:01,035 --> 00:03:03,259 and the smoke rising out of there 69 00:03:03,259 --> 00:03:05,435 looks like just some sort of gas, 70 00:03:05,435 --> 00:03:07,803 it's actually made of millions of tiny little particles, 71 00:03:07,803 --> 00:03:09,211 that enter the lungs. 72 00:03:09,211 --> 00:03:11,287 They're all foreign, they're all irritating, 73 00:03:12,028 --> 00:03:14,779 and the lung acts like a filter, these smoke particles 74 00:03:14,779 --> 00:03:17,686 are big enough to get trapped pretty early on. 75 00:03:18,154 --> 00:03:20,523 They're not small enough to get through the filter, 76 00:03:20,523 --> 00:03:22,330 all the way to the end of the acinus, 77 00:03:22,330 --> 00:03:25,818 so they kind of stay in this central acinar distribution, 78 00:03:25,818 --> 00:03:27,467 which then makes sense, that central acinar 79 00:03:27,467 --> 00:03:29,002 is related to smoking, 80 00:03:29,002 --> 00:03:30,379 and the inflammation you get from that. 81 00:03:30,379 --> 00:03:32,330 So if you look at the lungs as a whole, 82 00:03:32,330 --> 00:03:34,394 centriacinar is early on, 83 00:03:34,394 --> 00:03:37,446 and near the larger-caliber airways, like the bronchioles. 84 00:03:41,070 --> 00:03:43,172 Now the next one, panacinar. 85 00:03:43,882 --> 00:03:47,163 So panacinar is usually not induced by some sort 86 00:03:47,163 --> 00:03:49,276 of external factor; 87 00:03:49,754 --> 00:03:52,069 this problem arises out of the body itself. 88 00:03:52,729 --> 00:03:56,597 Here we have Alpha 1-antitrypsin deficiency. 89 00:03:57,050 --> 00:04:00,105 Remember, we said up there, this regulates the amount 90 00:04:00,105 --> 00:04:03,141 of elastase, namely to tone it down a little bit. 91 00:04:03,673 --> 00:04:06,393 So without it, the elastase is really unchecked; 92 00:04:06,393 --> 00:04:09,248 it just goes nuts, and eats up all the elastin 93 00:04:09,248 --> 00:04:10,868 in the tissues, everywhere. 94 00:04:11,576 --> 00:04:13,505 See this problem [unintelligible] earlier or later 95 00:04:13,505 --> 00:04:14,140 in the lungs, 96 00:04:14,140 --> 00:04:17,365 because it's inherent in all the tissues of the lungs. 97 00:04:17,769 --> 00:04:20,185 So everywhere the elastin's getting chewed up, 98 00:04:20,185 --> 00:04:21,861 everywhere there's elastic tissue. 99 00:04:22,313 --> 00:04:24,873 Just as a side note, Alpha 1-antitrypsin 100 00:04:24,873 --> 00:04:26,378 is made in the liver, 101 00:04:26,378 --> 00:04:28,425 and in this disease, when there's deficiency, 102 00:04:28,425 --> 00:04:30,024 that means something in the DNA, 103 00:04:30,024 --> 00:04:31,656 and the gene encoding for it, 104 00:04:31,656 --> 00:04:32,788 there's a mistake. 105 00:04:32,792 --> 00:04:35,978 So, all the misfolded protein can't leave the liver, 106 00:04:35,978 --> 00:04:37,243 leading to liver disease. 107 00:04:37,496 --> 00:04:39,224 But when we come to the lungs, 108 00:04:39,224 --> 00:04:41,880 we see panacinar emphysema.