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Let's say that these are your lungs. This is your right lung. This is your left lung. We're just going to label them upper and this will be lower. This will be the middle lobe. You're minding your own business and somebody coughs, and they get TB in your lungs. That TB gets inhaled, you breathe it in, and the location that the TB likes to go to, it's actually a pretty interesting thing, is it likes to go along these fissures that I'm drawing out here. These are the fissures; They separate the lobes of the lungs. They are kind of like the boundaries. The TB bacteria like to go near those fissures. They also actually like to go sub-pleural. Pleural indicates the outside layer of the lung. So, if it's sub, it's right underneath that outside layer. They like to go somewhere along the fissure and somewhere in the sub-pleural space; right on the edge. They're going to jump into some alveoli. Let me just draw it out for you here. You know, you've got millions of these guys; I'm going to draw a few more, just to make it really clear that these things are in packs. What's going to happen is, of course, you're going to have an immune response right away to this bacterium that's in there. You might have a macrophage coming along like that. This macrophage is going to pick up the bacteria that's now landed inside of that air sac, and it's going to take a journey through the tissue of the lung. It's going to go and drain down to a local lymph node. This is a local lymph node; a neighborhood lymph node. Let me label it right here; lymph node. That's the journey that the macrophage is going to take; not every single one, but some of them are going to go to the lymph node. What they do by doing that is, they actually carry with them the micro bacterium. This little bacterium is now carried along, going for the ride, and now the bacteria is in two spots. It's in the original spot where it landed in the lungs, but it's also in the lymph node because it got carried there by the macrophage. I should've mentioned this earlier, but let's assume that this is your primary infection. In other words, this is the first time that this person, or I guess it could be you or me, is breathing in the TB bacteria. What's going to happen is, there's going to be a reaction. The micro bacterium and the macrophages are going to start warring. They're going to fight. You're going to get this entire area turned into literally a battlefield, with dead micro bacterium and some dead macrophages. Some of your own cells are going to be part of this, but a lot of it is just going to be the bacteria. You're going to get some of this battlefield going on over here as well, in this lymph node. That's what it's going to turn into; a giant battlefield. If you look under a microscope, it actually looks like, well we call it a granuloma. That's the description that a pathologist might use for what we are actually describing here. The same thing is true for the lymph node. There's a little granuloma in there as well. If you were to peek inside of this granuloma, let's just actually erase the center out, if you were to peek inside, let's say I was to cut it open, what you would see is, inside of this granuloma is literally this mess; this goo that somebody at some point, thought looked like cheese. I'm not sure how they came up with that conclusion, but it kind of stuck. So, we call this caseous necrosis. Caseous literally refers to cheese. This is the same kind of cheese that might go on your crackers. Cheese, and you can think of it almost like cheesy death I guess; cheesy death for the necrosis part. I think I added an extra "e" there by accident. Let me fix that with a little hyphen. So, cheesy death. Because I'm naming things, let me go ahead and give you a couple more names. Ghon Focus; what the heck does that mean? Ghon Focus, actually named after Dr. Ghon. Ghon Focus is what we call this thing. It's termed a granuloma, and specifically here because it's a granuloma, which is more a broad term, is in the sub-pleural space, we said, and it's close to a fissure, and we suspect it's from TB. We would call it a Ghon Focus; it's the other name for it. Both of these, if you're trying to name both of these together, the lymph node that has a granuloma and the Ghon Focus, together make up what we call the Ghon Complex; Ghon complex. That just refers to both of the areas of disease. This is how disease starts, but what happens after time passes? Let me just slide this over a little bit. If we then take a little bit of passage of time. Let's say there are three options. Time has passed. What are the different possibilities? Well, let me actually go through and talk about micro bacterium; micro bacterium tuberculosis from the standpoint of what is going on. Actually, I just noticed, I have in the past made the mistake of using a capital T, but it should be a lower case t. Micro bacterium tuberculosis; three options. One option is that the bacterium may be dead. You may have killed it with your macrophages. Another option is that the bacterium is dormant; it's just lying in wait. The third option is that it's multiplying like crazy; it's actually going and dividing and dividing and dividing. The last one, actually, is going to look - if you looked on a chest x-ray, like this, you see lots of disease; this red indicates diseased tissue, not normal tissue. You might even see some large diseased lymph nodes. That's what it'd look like on a chest x-ray. These other two, on a chest x-ray, basically would look normal. If you were to look at a chest x-ray, this is what the three options would look like. The first two would look normal, and the third one would look like something is wrong. Actually, this is helpful, because remember, these two together, we call these, both situations we call them latent TB infection. Remember, we can't really easily distinguish the two because in both situations, you've had prior exposure to TB, and in both situations the x-ray looks normal. If you had some super ability to actually zoom in; let's say you looked under a microscope, you would notice one key difference between these two. This is not something you can see on a chest x-ray, you can see only if you had amazing vision and could look down at the microscopic level at somebody's lungs. You'd see macrophages, and in the top case where there are dead bacteria, the macrophages would look healthy and happy. In the case where you have dormant bacteria, you would actually see some bacteria there; some red, live bacteria. That's the key difference between these two situations. Again, both of them we call latent TB infection. In this scenario, the bottom one, is going to be called progressive because things are slowly but surely getting worse; you can see more disease on the chest x-ray. Primary, with a 1 and a degree sign, infection; this is the name for this, progressive primary infection. It sounds a lot like what we had named that here, with primary infection, but the word progressive tells us that things are actually getting worse. The disease is getting more nasty. Now, let's actually play out the rest of this. Let's think about what will happen with the dormant situation. I wrote out, or drew this out, earlier. Let's say more time is passing, of course. Maybe years have gone by. This person has had live bacteria in their lungs for years and years; nothing has happened. Now, they have what we call reactivation; maybe it's because their immune system is not working properly, or maybe they have another disease. Who knows why, but all of a sudden, now the bacteria, the TB bacteria, are going to come out with a vengeance. There's going to be a cavity that forms; usually in the upper lobes. A cavity that forms up here. It's going to be packed full of TB bacteria. This person, you could imagine, if they coughed, they're going to be coughing out lots and lots of these little bacteria that i'm drawing. Around that area there's a lot of disease; a lot of disease in this area and it's very, very distinct. If you see cavities, and you see lots and lots of disease, you're really going to be worried that this person might have what we call progressive secondary infection. The reason I'm saying secondary is because, again, this is happening separate from that primary infection; this is happening sometimes years later. Another way you can actually have this happen is through what we call a secondary infection. Maybe you actually literally get more TB. Maybe you're on a bus or a boat, and a second person decides to cough and TB gets into your lungs through breathing it in. That's another way to actually get progressive secondary infection. You can also think that this is re-infection, because you basically got re-infected with the same bug. The thing that ties reactivation together with re-infection is that in both situations your immune system has at some point in the past been exposed to TB. We think that's the main reason why you see these cavities, and you see so much disease. That's a really horrible infection to get. So, thinking about this a little bit more broadly then, both the progressive primary infection, and the progressive secondary infection, who are the folks that you'd be most worried getting these diseases? I always worry about HIV patients before any other group because we know that HIV and TB is a really, really bad combination. They're at high risk for getting progressive disease; both primary, which is at the time that they got the first infection with TB, or secondary which could be years later.