WEBVTT 00:00:02.071 --> 00:00:04.679 Voiceover: So the two categories that we assign to emphysema, 00:00:04.679 --> 00:00:07.398 the centriacinar and the panacinar, 00:00:07.398 --> 00:00:09.299 they're basically referring to geography. 00:00:09.510 --> 00:00:11.590 It's like saying, my city's flooded, 00:00:11.590 --> 00:00:14.534 and is it contained to the central streets, the main street, 00:00:14.534 --> 00:00:15.762 or is it everywhere? 00:00:16.198 --> 00:00:18.674 So basically, it's asking, "Where is the emphysema?" 00:00:19.062 --> 00:00:20.967 So a little Latin review, we have "pan," 00:00:20.967 --> 00:00:22.310 which means everywhere, 00:00:22.310 --> 00:00:23.906 and "centri," so "center." 00:00:24.598 --> 00:00:26.802 Now, what on earth is an "acinar?" 00:00:26.950 --> 00:00:29.158 And basically, that's a geographical term too, 00:00:29.158 --> 00:00:31.026 and this is an "acinus." 00:00:32.071 --> 00:00:34.194 To orient ourselves, let's draw the lungs. 00:00:34.310 --> 00:00:37.638 We have the trachea here, and the two big bronchi, 00:00:37.638 --> 00:00:40.737 so you have your lobe of lung here, and lobe of lung here. 00:00:40.837 --> 00:00:43.637 The bronchi are kind of like your tree trunks, 00:00:43.637 --> 00:00:45.973 and as they start to branch off like this, 00:00:45.973 --> 00:00:48.998 the smaller airways here are called "bronchioles," 00:00:48.998 --> 00:00:51.382 and that's basically the level we're at right here. 00:00:51.382 --> 00:00:54.757 Here is our bronchiole, and the rest of this branch 00:00:54.757 --> 00:00:57.361 that I've drawn, is just the rest of the airway. 00:00:57.493 --> 00:01:00.305 So here, we have our alveoli cluster. 00:01:02.182 --> 00:01:04.549 So there are many many countless branches 00:01:04.549 --> 00:01:08.428 of acini in the lungs, but this is what one would look like. 00:01:08.428 --> 00:01:12.085 So that tells us centriacinar versus panacinar, 00:01:12.085 --> 00:01:14.910 we're talking about where, in this, are we? 00:01:15.246 --> 00:01:17.213 So in this normal acinus that I've drawn, 00:01:17.213 --> 00:01:19.597 you can see the tightly, little coiled structures here 00:01:19.597 --> 00:01:22.377 in the alveoli, and along the airways too. 00:01:23.150 --> 00:01:25.293 This elastic, coiled shape is possible 00:01:25.293 --> 00:01:27.593 because of our protein, elastin. 00:01:27.885 --> 00:01:31.085 Elastin is cleaved by elastase, 00:01:31.085 --> 00:01:34.413 which is this protein inhibitor, which is good usually, 00:01:34.413 --> 00:01:36.205 because we want the tissue to turn over, 00:01:36.205 --> 00:01:37.577 old ones to be eaten up. 00:01:37.773 --> 00:01:41.821 And this whole system is controlled by Alpha 1-antitrypsin, 00:01:41.821 --> 00:01:44.333 which is a compound made in the liver, and it's job 00:01:44.333 --> 00:01:46.633 is to regulate the amount of elastase. 00:01:47.341 --> 00:01:51.293 So, by inhibiting the elastase, it inhibits the elastin, 00:01:51.293 --> 00:01:54.654 the antitrypsin lets there be more elastin. 00:01:55.837 --> 00:01:58.717 So whether we're going to have centriacinar here, 00:01:58.717 --> 00:02:01.692 or panacinar destruction of elastin, 00:02:01.692 --> 00:02:03.356 fully depends on the pathophysiology 00:02:03.356 --> 00:02:05.933 of why is there so much elastase? 00:02:05.933 --> 00:02:07.560 Why is elastin getting destroyed? 00:02:08.781 --> 00:02:10.953 So first, let's take a look at centriacinar. 00:02:11.340 --> 00:02:14.636 And this is what it looks like, so I've draw the same acinus 00:02:14.636 --> 00:02:15.852 that we have up there, 00:02:15.852 --> 00:02:17.679 but because of the lack of elastin in it, 00:02:17.679 --> 00:02:19.912 there're fewer of the walls to begin with. 00:02:20.028 --> 00:02:22.732 And, whatever walls there are left, it's because 00:02:22.732 --> 00:02:24.765 it's so floppy, that's why it looks bigger like that, 00:02:24.765 --> 00:02:27.064 it just doesn't hold that nice shape. 00:02:27.500 --> 00:02:30.364 So this is what we call "centriacinar distribution," 00:02:30.364 --> 00:02:32.251 as you can see, geographically, 00:02:32.251 --> 00:02:34.090 it's earlier, it's not everywhere. 00:02:34.476 --> 00:02:36.780 Centriacinar is really related to inflammation, 00:02:36.780 --> 00:02:40.119 which is the first pathophysiology of emphysema. 00:02:40.527 --> 00:02:42.651 Now inflammation recruits neutrophils, 00:02:42.651 --> 00:02:44.843 these white blood cells that flight inflammation 00:02:44.843 --> 00:02:46.103 everywhere in the body. 00:02:46.203 --> 00:02:47.819 But when they get to the lungs, the neutrophils 00:02:47.819 --> 00:02:51.480 make elastase, that's the whole culprit here. 00:02:51.883 --> 00:02:54.664 So it's too much elastase, from too much inflammation. 00:02:54.683 --> 00:02:58.215 And the way we'd get that, most commonly, is from smoking. 00:02:59.003 --> 00:03:01.035 So even though, when you see somebody smoking, 00:03:01.035 --> 00:03:03.259 and the smoke rising out of there 00:03:03.259 --> 00:03:05.435 looks like just some sort of gas, 00:03:05.435 --> 00:03:07.803 it's actually made of millions of tiny little particles, 00:03:07.803 --> 00:03:09.211 that enter the lungs. 00:03:09.211 --> 00:03:11.287 They're all foreign, they're all irritating, 00:03:12.028 --> 00:03:14.779 and the lung acts like a filter, these smoke particles 00:03:14.779 --> 00:03:17.686 are big enough to get trapped pretty early on. 00:03:18.154 --> 00:03:20.523 They're not small enough to get through the filter, 00:03:20.523 --> 00:03:22.330 all the way to the end of the acinus, 00:03:22.330 --> 00:03:25.818 so they kind of stay in this central acinar distribution, 00:03:25.818 --> 00:03:27.467 which then makes sense, that central acinar 00:03:27.467 --> 00:03:29.002 is related to smoking, 00:03:29.002 --> 00:03:30.379 and the inflammation you get from that. 00:03:30.379 --> 00:03:32.330 So if you look at the lungs as a whole, 00:03:32.330 --> 00:03:34.394 centriacinar is early on, 00:03:34.394 --> 00:03:37.446 and near the larger-caliber airways, like the bronchioles. 00:03:41.070 --> 00:03:43.172 Now the next one, panacinar. 00:03:43.882 --> 00:03:47.163 So panacinar is usually not induced by some sort 00:03:47.163 --> 00:03:49.276 of external factor; 00:03:49.754 --> 00:03:52.069 this problem arises out of the body itself. 00:03:52.729 --> 00:03:56.597 Here we have Alpha 1-antitrypsin deficiency. 00:03:57.050 --> 00:04:00.105 Remember, we said up there, this regulates the amount 00:04:00.105 --> 00:04:03.141 of elastase, namely to tone it down a little bit. 00:04:03.673 --> 00:04:06.393 So without it, the elastase is really unchecked; 00:04:06.393 --> 00:04:09.248 it just goes nuts, and eats up all the elastin 00:04:09.248 --> 00:04:10.868 in the tissues, everywhere. 00:04:11.576 --> 00:04:13.505 See this problem [unintelligible] earlier or later 00:04:13.505 --> 00:04:14.140 in the lungs, 00:04:14.140 --> 00:04:17.365 because it's inherent in all the tissues of the lungs. 00:04:17.769 --> 00:04:20.185 So everywhere the elastin's getting chewed up, 00:04:20.185 --> 00:04:21.861 everywhere there's elastic tissue. 00:04:22.313 --> 00:04:24.873 Just as a side note, Alpha 1-antitrypsin 00:04:24.873 --> 00:04:26.378 is made in the liver, 00:04:26.378 --> 00:04:28.425 and in this disease, when there's deficiency, 00:04:28.425 --> 00:04:30.024 that means something in the DNA, 00:04:30.024 --> 00:04:31.656 and the gene encoding for it, 00:04:31.656 --> 00:04:32.788 there's a mistake. 00:04:32.792 --> 00:04:35.978 So, all the misfolded protein can't leave the liver, 00:04:35.978 --> 00:04:37.243 leading to liver disease. 00:04:37.496 --> 00:04:39.224 But when we come to the lungs, 00:04:39.224 --> 00:04:41.880 we see panacinar emphysema.