[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:02.07,0:00:04.68,Default,,0000,0000,0000,,Voiceover: So the two categories\Nthat we assign to emphysema,
Dialogue: 0,0:00:04.68,0:00:07.40,Default,,0000,0000,0000,,the centriacinar and the panacinar,
Dialogue: 0,0:00:07.40,0:00:09.30,Default,,0000,0000,0000,,they're basically referring to geography.
Dialogue: 0,0:00:09.51,0:00:11.59,Default,,0000,0000,0000,,It's like saying, my city's flooded,
Dialogue: 0,0:00:11.59,0:00:14.53,Default,,0000,0000,0000,,and is it contained to the\Ncentral streets, the main street,
Dialogue: 0,0:00:14.53,0:00:15.76,Default,,0000,0000,0000,,or is it everywhere?
Dialogue: 0,0:00:16.20,0:00:18.67,Default,,0000,0000,0000,,So basically, it's asking,\N"Where is the emphysema?"
Dialogue: 0,0:00:19.06,0:00:20.97,Default,,0000,0000,0000,,So a little Latin review, we have "pan,"
Dialogue: 0,0:00:20.97,0:00:22.31,Default,,0000,0000,0000,,which means everywhere,
Dialogue: 0,0:00:22.31,0:00:23.91,Default,,0000,0000,0000,,and "centri," so "center."
Dialogue: 0,0:00:24.60,0:00:26.80,Default,,0000,0000,0000,,Now, what on earth is an "acinar?"
Dialogue: 0,0:00:26.95,0:00:29.16,Default,,0000,0000,0000,,And basically, that's a\Ngeographical term too,
Dialogue: 0,0:00:29.16,0:00:31.03,Default,,0000,0000,0000,,and this is an "acinus."
Dialogue: 0,0:00:32.07,0:00:34.19,Default,,0000,0000,0000,,To orient ourselves, let's draw the lungs.
Dialogue: 0,0:00:34.31,0:00:37.64,Default,,0000,0000,0000,,We have the trachea here,\Nand the two big bronchi,
Dialogue: 0,0:00:37.64,0:00:40.74,Default,,0000,0000,0000,,so you have your lobe of lung\Nhere, and lobe of lung here.
Dialogue: 0,0:00:40.84,0:00:43.64,Default,,0000,0000,0000,,The bronchi are kind of\Nlike your tree trunks,
Dialogue: 0,0:00:43.64,0:00:45.97,Default,,0000,0000,0000,,and as they start to branch off like this,
Dialogue: 0,0:00:45.97,0:00:48.100,Default,,0000,0000,0000,,the smaller airways here\Nare called "bronchioles,"
Dialogue: 0,0:00:48.100,0:00:51.38,Default,,0000,0000,0000,,and that's basically the\Nlevel we're at right here.
Dialogue: 0,0:00:51.38,0:00:54.76,Default,,0000,0000,0000,,Here is our bronchiole,\Nand the rest of this branch
Dialogue: 0,0:00:54.76,0:00:57.36,Default,,0000,0000,0000,,that I've drawn, is just\Nthe rest of the airway.
Dialogue: 0,0:00:57.49,0:01:00.30,Default,,0000,0000,0000,,So here, we have our alveoli cluster.
Dialogue: 0,0:01:02.18,0:01:04.55,Default,,0000,0000,0000,,So there are many many countless branches
Dialogue: 0,0:01:04.55,0:01:08.43,Default,,0000,0000,0000,,of acini in the lungs, but this\Nis what one would look like.
Dialogue: 0,0:01:08.43,0:01:12.08,Default,,0000,0000,0000,,So that tells us centriacinar\Nversus panacinar,
Dialogue: 0,0:01:12.08,0:01:14.91,Default,,0000,0000,0000,,we're talking about\Nwhere, in this, are we?
Dialogue: 0,0:01:15.25,0:01:17.21,Default,,0000,0000,0000,,So in this normal acinus that I've drawn,
Dialogue: 0,0:01:17.21,0:01:19.60,Default,,0000,0000,0000,,you can see the tightly,\Nlittle coiled structures here
Dialogue: 0,0:01:19.60,0:01:22.38,Default,,0000,0000,0000,,in the alveoli, and along the airways too.
Dialogue: 0,0:01:23.15,0:01:25.29,Default,,0000,0000,0000,,This elastic, coiled shape is possible
Dialogue: 0,0:01:25.29,0:01:27.59,Default,,0000,0000,0000,,because of our protein, elastin.
Dialogue: 0,0:01:27.88,0:01:31.08,Default,,0000,0000,0000,,Elastin is cleaved by elastase,
Dialogue: 0,0:01:31.08,0:01:34.41,Default,,0000,0000,0000,,which is this protein inhibitor,\Nwhich is good usually,
Dialogue: 0,0:01:34.41,0:01:36.20,Default,,0000,0000,0000,,because we want the tissue to turn over,
Dialogue: 0,0:01:36.20,0:01:37.58,Default,,0000,0000,0000,,old ones to be eaten up.
Dialogue: 0,0:01:37.77,0:01:41.82,Default,,0000,0000,0000,,And this whole system is\Ncontrolled by Alpha 1-antitrypsin,
Dialogue: 0,0:01:41.82,0:01:44.33,Default,,0000,0000,0000,,which is a compound made\Nin the liver, and it's job
Dialogue: 0,0:01:44.33,0:01:46.63,Default,,0000,0000,0000,,is to regulate the amount of elastase.
Dialogue: 0,0:01:47.34,0:01:51.29,Default,,0000,0000,0000,,So, by inhibiting the elastase,\Nit inhibits the elastin,
Dialogue: 0,0:01:51.29,0:01:54.65,Default,,0000,0000,0000,,the antitrypsin lets\Nthere be more elastin.
Dialogue: 0,0:01:55.84,0:01:58.72,Default,,0000,0000,0000,,So whether we're going to\Nhave centriacinar here,
Dialogue: 0,0:01:58.72,0:02:01.69,Default,,0000,0000,0000,,or panacinar destruction of elastin,
Dialogue: 0,0:02:01.69,0:02:03.36,Default,,0000,0000,0000,,fully depends on the pathophysiology
Dialogue: 0,0:02:03.36,0:02:05.93,Default,,0000,0000,0000,,of why is there so much elastase?
Dialogue: 0,0:02:05.93,0:02:07.56,Default,,0000,0000,0000,,Why is elastin getting destroyed?
Dialogue: 0,0:02:08.78,0:02:10.95,Default,,0000,0000,0000,,So first, let's take a\Nlook at centriacinar.
Dialogue: 0,0:02:11.34,0:02:14.64,Default,,0000,0000,0000,,And this is what it looks like,\Nso I've draw the same acinus
Dialogue: 0,0:02:14.64,0:02:15.85,Default,,0000,0000,0000,,that we have up there,
Dialogue: 0,0:02:15.85,0:02:17.68,Default,,0000,0000,0000,,but because of the lack of elastin in it,
Dialogue: 0,0:02:17.68,0:02:19.91,Default,,0000,0000,0000,,there're fewer of the walls to begin with.
Dialogue: 0,0:02:20.03,0:02:22.73,Default,,0000,0000,0000,,And, whatever walls there\Nare left, it's because
Dialogue: 0,0:02:22.73,0:02:24.76,Default,,0000,0000,0000,,it's so floppy, that's why\Nit looks bigger like that,
Dialogue: 0,0:02:24.76,0:02:27.06,Default,,0000,0000,0000,,it just doesn't hold that nice shape.
Dialogue: 0,0:02:27.50,0:02:30.36,Default,,0000,0000,0000,,So this is what we call\N"centriacinar distribution,"
Dialogue: 0,0:02:30.36,0:02:32.25,Default,,0000,0000,0000,,as you can see, geographically,
Dialogue: 0,0:02:32.25,0:02:34.09,Default,,0000,0000,0000,,it's earlier, it's not everywhere.
Dialogue: 0,0:02:34.48,0:02:36.78,Default,,0000,0000,0000,,Centriacinar is really\Nrelated to inflammation,
Dialogue: 0,0:02:36.78,0:02:40.12,Default,,0000,0000,0000,,which is the first\Npathophysiology of emphysema.
Dialogue: 0,0:02:40.53,0:02:42.65,Default,,0000,0000,0000,,Now inflammation recruits neutrophils,
Dialogue: 0,0:02:42.65,0:02:44.84,Default,,0000,0000,0000,,these white blood cells\Nthat flight inflammation
Dialogue: 0,0:02:44.84,0:02:46.10,Default,,0000,0000,0000,,everywhere in the body.
Dialogue: 0,0:02:46.20,0:02:47.82,Default,,0000,0000,0000,,But when they get to the\Nlungs, the neutrophils
Dialogue: 0,0:02:47.82,0:02:51.48,Default,,0000,0000,0000,,make elastase, that's\Nthe whole culprit here.
Dialogue: 0,0:02:51.88,0:02:54.66,Default,,0000,0000,0000,,So it's too much elastase,\Nfrom too much inflammation.
Dialogue: 0,0:02:54.68,0:02:58.22,Default,,0000,0000,0000,,And the way we'd get that,\Nmost commonly, is from smoking.
Dialogue: 0,0:02:59.00,0:03:01.04,Default,,0000,0000,0000,,So even though, when you\Nsee somebody smoking,
Dialogue: 0,0:03:01.04,0:03:03.26,Default,,0000,0000,0000,,and the smoke rising out of there
Dialogue: 0,0:03:03.26,0:03:05.44,Default,,0000,0000,0000,,looks like just some sort of gas,
Dialogue: 0,0:03:05.44,0:03:07.80,Default,,0000,0000,0000,,it's actually made of millions\Nof tiny little particles,
Dialogue: 0,0:03:07.80,0:03:09.21,Default,,0000,0000,0000,,that enter the lungs.
Dialogue: 0,0:03:09.21,0:03:11.29,Default,,0000,0000,0000,,They're all foreign,\Nthey're all irritating,
Dialogue: 0,0:03:12.03,0:03:14.78,Default,,0000,0000,0000,,and the lung acts like a\Nfilter, these smoke particles
Dialogue: 0,0:03:14.78,0:03:17.69,Default,,0000,0000,0000,,are big enough to get\Ntrapped pretty early on.
Dialogue: 0,0:03:18.15,0:03:20.52,Default,,0000,0000,0000,,They're not small enough\Nto get through the filter,
Dialogue: 0,0:03:20.52,0:03:22.33,Default,,0000,0000,0000,,all the way to the end of the acinus,
Dialogue: 0,0:03:22.33,0:03:25.82,Default,,0000,0000,0000,,so they kind of stay in this\Ncentral acinar distribution,
Dialogue: 0,0:03:25.82,0:03:27.47,Default,,0000,0000,0000,,which then makes sense,\Nthat central acinar
Dialogue: 0,0:03:27.47,0:03:29.00,Default,,0000,0000,0000,,is related to smoking,
Dialogue: 0,0:03:29.00,0:03:30.38,Default,,0000,0000,0000,,and the inflammation you get from that.
Dialogue: 0,0:03:30.38,0:03:32.33,Default,,0000,0000,0000,,So if you look at the lungs as a whole,
Dialogue: 0,0:03:32.33,0:03:34.39,Default,,0000,0000,0000,,centriacinar is early on,
Dialogue: 0,0:03:34.39,0:03:37.45,Default,,0000,0000,0000,,and near the larger-caliber\Nairways, like the bronchioles.
Dialogue: 0,0:03:41.07,0:03:43.17,Default,,0000,0000,0000,,Now the next one, panacinar.
Dialogue: 0,0:03:43.88,0:03:47.16,Default,,0000,0000,0000,,So panacinar is usually\Nnot induced by some sort
Dialogue: 0,0:03:47.16,0:03:49.28,Default,,0000,0000,0000,,of external factor;
Dialogue: 0,0:03:49.75,0:03:52.07,Default,,0000,0000,0000,,this problem arises\Nout of the body itself.
Dialogue: 0,0:03:52.73,0:03:56.60,Default,,0000,0000,0000,,Here we have Alpha\N1-antitrypsin deficiency.
Dialogue: 0,0:03:57.05,0:04:00.10,Default,,0000,0000,0000,,Remember, we said up there,\Nthis regulates the amount
Dialogue: 0,0:04:00.10,0:04:03.14,Default,,0000,0000,0000,,of elastase, namely to\Ntone it down a little bit.
Dialogue: 0,0:04:03.67,0:04:06.39,Default,,0000,0000,0000,,So without it, the elastase\Nis really unchecked;
Dialogue: 0,0:04:06.39,0:04:09.25,Default,,0000,0000,0000,,it just goes nuts, and\Neats up all the elastin
Dialogue: 0,0:04:09.25,0:04:10.87,Default,,0000,0000,0000,,in the tissues, everywhere.
Dialogue: 0,0:04:11.58,0:04:13.50,Default,,0000,0000,0000,,See this problem\N[unintelligible] earlier or later
Dialogue: 0,0:04:13.50,0:04:14.14,Default,,0000,0000,0000,,in the lungs,
Dialogue: 0,0:04:14.14,0:04:17.36,Default,,0000,0000,0000,,because it's inherent in all\Nthe tissues of the lungs.
Dialogue: 0,0:04:17.77,0:04:20.18,Default,,0000,0000,0000,,So everywhere the elastin's\Ngetting chewed up,
Dialogue: 0,0:04:20.18,0:04:21.86,Default,,0000,0000,0000,,everywhere there's elastic tissue.
Dialogue: 0,0:04:22.31,0:04:24.87,Default,,0000,0000,0000,,Just as a side note, Alpha 1-antitrypsin
Dialogue: 0,0:04:24.87,0:04:26.38,Default,,0000,0000,0000,,is made in the liver,
Dialogue: 0,0:04:26.38,0:04:28.42,Default,,0000,0000,0000,,and in this disease,\Nwhen there's deficiency,
Dialogue: 0,0:04:28.42,0:04:30.02,Default,,0000,0000,0000,,that means something in the DNA,
Dialogue: 0,0:04:30.02,0:04:31.66,Default,,0000,0000,0000,,and the gene encoding for it,
Dialogue: 0,0:04:31.66,0:04:32.79,Default,,0000,0000,0000,,there's a mistake.
Dialogue: 0,0:04:32.79,0:04:35.98,Default,,0000,0000,0000,,So, all the misfolded protein\Ncan't leave the liver,
Dialogue: 0,0:04:35.98,0:04:37.24,Default,,0000,0000,0000,,leading to liver disease.
Dialogue: 0,0:04:37.50,0:04:39.22,Default,,0000,0000,0000,,But when we come to the lungs,
Dialogue: 0,0:04:39.22,0:04:41.88,Default,,0000,0000,0000,,we see panacinar emphysema.