# Tuberculosis | Clinical Medicine ## Метаданные - **Канал:** Ninja Nerd - **YouTube:** https://www.youtube.com/watch?v=Qjo9F6Uuca8 - **Дата:** 28.04.2026 - **Длительность:** 2:22:35 - **Просмотры:** 27,634 ## Описание Premium Member Resources: https://ninjanerd.org Ninja Nerds! In this lecture, Zach Murphy delivers a comprehensive, high-yield breakdown of Tuberculosis, guiding you through the clinical reasoning required to recognize, diagnose, and manage one of the most important infectious diseases worldwide. This video builds a strong framework for understanding how Mycobacterium tuberculosis infects the body, why it can remain latent for years, and how it presents when it becomes active disease. We begin by reviewing the microbiology and transmission of tuberculosis, including its acid-fast cell wall, airborne spread, and the key risk factors that predispose patients to infection, such as immunosuppression, close living quarters, and underlying lung disease. Zach then walks through the pathophysiology of primary infection, focusing on granuloma formation, the role of cell-mediated immunity, and how latent tuberculosis develops as the immune system attempts to contain the organism. Next, the lecture transitions to active tuberculosis, emphasizing the classic and subtle clinical presentations, including chronic cough, hemoptysis, fever, night sweats, and weight loss. You will learn how to approach diagnosis using screening tests such as the tuberculin skin test and interferon-gamma release assays, followed by confirmatory testing with imaging and microbiologic studies. Zach also highlights key radiographic patterns, including upper lobe cavitary lesions and miliary dissemination, and explains how to distinguish latent from active disease in a clinically meaningful way. The lecture then focuses on treatment strategies, including first-line multidrug therapy, mechanisms of action, and the importance of adherence to prevent resistance. Zach breaks down high-yield drug toxicities such as hepatotoxicity, optic neuritis, and peripheral neuropathy, along with how to monitor and manage these complications. Special attention is given to multidrug-resistant tuberculosis and considerations in patients with human immunodeficiency virus co-infection. Enjoy the lecture, and please support us below! Table of Contents: 0:00 Lab 0:25 Etiology of Tuberculosis (TB) 12:49 Risk Factors for TB 27:01 Pathophysiology of TB 57:52 Latent vs. Active TB 1:14:43 Clinical Findings and Complications of TB 1:32:20 Diagnostic Approach to TB 2:09:24 Treatment of TB 2:22:05 Comment, Like, SUBSCRIBE! 🌐 Official Links Website: https://www.ninjanerd.org Podcast: https://podcast.ninjanerd.org Store: https://merch.ninjanerd.org 📱 Social Media https://www.tiktok.com/@ninjanerdlectures https://www.instagram.com/ninjanerdlectures https://www.facebook.com/ninjanerdlectures https://x.com/ninjanerdsci/ https://www.linkedin.com/company/ninja-nerd/ 💬 Join Our Community Discord: https://discord.gg/3srTG4dngW #ninjanerd #infectiousdisease #tuberculosis ## Содержание ### [0:00](https://www.youtube.com/watch?v=Qjo9F6Uuca8) Lab What's up, ninja nerds? In this video today, we're going to be talking about tuberculosis. And if you guys like this video, please support us. You can hit the like button, you can comment down in the comment section, you can subscribe, or you can go to our website. On our website, we got things like notes, illustrations, we got quizzes. Go check it out. There's a lot to learn. All right, let's get into TB. When we talk about TB, first thing we need to know is ### [0:25](https://www.youtube.com/watch?v=Qjo9F6Uuca8&t=25s) Etiology of Tuberculosis (TB) what's the thing that's causing it? What is that particular pathogen? The particular pathogen is actually called mcoacterium tuberculosis. That's really important to remember. So the primary pathogen is called mcoacterium tuberculosis. Now there's a lot of different types of mcoacterium species, but mcoacterium tuberculosis is definitely it's a pretty scary one. When we talk about this one, what makes this one super unique is when you actually zoom in on its overall cell wall, there's a couple different components that are really critical. So going from the most inner portion to the outer portion there's a couple different layers. One here we have just the overall cell membrane right that's kind of that just the phospholipid billayer if you will. Then after that we have this pepidoglycin layer. All right so then we have something called a pepido glycen layer. Then there's technically something called arabino galactin layer. And then the most important layer is called the micolic acids. So this is called micolic acids. Now the micolic acids are probably the most important thing to remember when we talk about this one. Micol acids really what's interesting about these is that they allow for mcoacterium to be I'd say whenever you're doing your special types of staining. So when you go through different types of grandstanding procedures, use things like crystal violet, use things like carbal fusion. And generally what it's supposed to do is supposed to stain the bacteria kind of like a reddish pinkish color. And then what you do is you actually undergo a process where you kind of use this kind of acid alcohol to decolorize it and remove that dye out. What happens with micolic acids is that they really resist that decolorization. And because they resist decolorization with what's called your acid fast kind of like staining, which is again we use acid alcohol, they don't get that red color out. They remain kind of a well actually they kind of retain this reddish color with a bluish background. And so micolic acids make these bacteria what we call acid fast. All right, so let's write that down. This makes it a acid fast bacteria. And this is going to become pretty critical because when we actually start getting into um the actual testing process where we do something called acidfast basillus smears. One of the be things about you know generally mcoacterial species is that when you again go through them you give them this kind of reddish pinkish dye you give them an acid alcohol and that should wash all of that off. any kind of mcoacterial species exhibit a lot of these micolic acids and they resist that decolorization. So again because of that they stay what does this mean when they're acidfast is they stay red. So let's actually write that out here they remain red and all that tells me is that there is the presence of mcoacterial species. Doesn't tell me if it's TB. It like avium or any of these other different types. It just tells me hey there's a mcoacterium present. Now, one of the other really important things about miccoacterium is not only just its cell wall, which is rich in these micolic acids. Micol acids makes it pretty hardy types of pathogen, but also it's got other unique characteristics. Naturally, what we look at with these bacteria is something called their doubling time. And we look at this logarithmic scale, which looks at time on the x-axis and logarithmic number of cells on the y- axis. And generally, bacteria have this type of growth pattern. What we notice about mcoacterium tuberculosis is it has a very long uh doubling time or prolonged takes a really long time for this thing to grow. So it has a very long doubling time which means it has a slow growth process. One of the downsides about this is that well there's two things. One is whenever you try to do cultures to actually see if you can grow this type of particular bacteria, it takes a really long time. So often times when we try to do cultures for these patients, the clinical application is that it takes sometimes two sometimes like six weeks for cultures to grow out. And that's kind of one of the potential downsides. And so that's kind of a clinical application of their really long doubling time is since it takes super long for these things to grow. When you try to culture these things, it just takes a really really long time. But these are the gold standard. Another thing about tuberculosis is it's predilction. So mcoacterium tuberculosis is what's called an obligate a-obbe. So, it has a long doubling time, but it has an it's an obligate a-obbe, which means it really needs and it really prefers to be in high levels of oxygen tension. If you look at the lungs and we kind of imagine here for the lungs, all right, here we have the different parts of the lungs. You have your upper lobes, you have your middle lobe just here on the right side, and then you have your lower loes. Which of the loes has the highest oxygen tension? It's generally the upper lobes. And so what happens is mcoacterial species not only do they have a very long time period where we start off with this bacteria and then we double it right but also they prefer the upper lobes because that's where the highest oxygen tension is present. So, one of the other things about this is because it's an obligate a- robe, it has a preference for the apex of the lungs because of why that has the highest oxygen tension. So, that's going to be where it wants to live. It wants to be in those areas where there's going to be a lot of oxygen. All right. So, so far we got mcoacterium tuberculosis. One of the most important things about it with respect to its overall structure is the micolic acid residues makes it pretty hardy. Also makes it really unique that whenever you take mcoacterial species and you uh undergo decolorization and then you try to again give them this new counter stain, they don't take that up. They remain that reddish color. Again, they have a really long doubling time, which kind of sucks when you got to culture these patients because it means it's going to take a while for you to actually get these to grow out. That also means that you got to put these patients on antibiotics for a really long time as well. So there actually another component to that. It's an obligate a-ro which areas of the lungs? It prefers the apex of the lungs because of the high oxygen tension. There's a third component to these that makes them really scary. The other component is that they have a lot of what's called virulence factors. All these mean is that essentially the mcoacterium have really nasty kinds of weapons that make it able to evade the immune system and make it really hard for the immune system to try to be able to kill these species. So what are these? Well, one of them is here in this S. So it's called a sulfatide. So let's say here you have a macrofase, right? Here's our macrofase. And this macrofase generally what it wants to undergo is a process called uh making a fagosome. So in other words what happens is let's say you take this mcoacterium species up. It under goes fagocytosis. So what does that mean? It takes it from the outside which is out here engulfs it and brings it inside. That's called a fagosome. And the process by which we go to do this is called fagocytosis. Then it wants to fuse with this little green structure. What's that called? A lome. So then we should make a fagago, which is the fusion of the fagosome and the lome. And what happens is the purpose of doing this is that you take all of these really nasty harsh loal enzymes and you mix it with the fagosome that contains the bacteria. And the goal is to do what? is to cause killing, right? It's to basically kill the mcoacterium tuberculosis. We'll put MTB. That's the goal is to kill the mcoacterium tuberculosis by using this fagalosome. Well, what happens is it has this thing inside of it and it's called a sulfatide. So again, what is it going to be over here? It has something called a sulfatide. And sulfatide is essentially the virulence factoring that inhibits. So they have the presence of this thing called a sulfatide. And the sulfatide inhibits at what point in this process? It inhibits the fusion of the fagosome and the lysosome. So you don't get this process. Therefore you can't have a really easy time killing the mcoacterium tuberculosis. And so this becomes more challenging. You see how that pretty much allows them to essentially kind of evade the immune system. Another thing is when you have just a couple of these by themselves, right, you just got one dude just hanging around and it's by itself. It's more susceptible to getting jacked up. So because of that, what these things do is they carry this kind of molecule on them. And this is called chord factor. And chord factor is essentially kind of like a glue. That's the way I want you guys to think about It's like a glue and essentially what it does is it does two things. One is it really helps to enhance your macrofase involvement and it also helps to really inhibit neutrfils. But one of the biggest things about this chord factor is it really causes what's called serpentine kind of growth or serpentine formation is what I want you to remember. So it causes serpentine formation or serpentine cords of the mcoacterium tuberculosis. So essentially this thing acts like a little glue between these guys and then they can grow and almost give you like this. Well, if you kind of think about it, it's maybe a little bit of a stretch with my drawing, but the serpentine cord which is all of these mcoacterial species kind of linked together. It's really hard for a macroofage to be able to defend against this. All right? As compared to just one of these by themselves. So, it's a whole group of friends taking on this kind of like macrofage versus just one or two of them by themselves. All right? So, that's kind of the benefit of this is that it just makes it harder for the macroofages to fight against them. So, what we get out of this is that mcoacterium tuberculosis is a pretty it's a pretty tough dude. All right. It has the capability of having micolic acids which makes it kind of resistant, right? But also it also really makes it kind of interesting with very unique features when it comes to diagnosis. We know about some very unique characteristics of it. One is it takes a long time for it to be able to grow and because of that there's two downsides. One is that it takes a long time for us to get cultures and it also completely clear the infection. So we should actually write that down. So there's actually two components here. One is it takes time for it to grow and the other one is it takes time for the uh for the infection to clear with antibiotics. Takes time to clear the mcoacterium tuberculosis with antibiotics. You'll see whenever we get to the actual treatment section, people have to be on these antibiotics for sometimes 3 months, 6 months, 9 months. It really depends. That's an insanely long time and it probably has something to do with that lung doubling time. All right, we know it prefers the upper lobes of the lung. That's going to come in really critical when we talk about what's called reactivation TB. And also one of the big things here is this thing is pretty hardy. Besides the micolic acids, it has these things called sulfatides and cord factor which basically allow for it to kind of become more hearty and make it harder for the immune system of the host to fight against it. Now we know the pathogen that basically can cause this problem. The question is how do we get it and how does it actually cause disease? Because you don't hear about mcoacterium tuberculosis like a ton. Well, one of ### [12:49](https://www.youtube.com/watch?v=Qjo9F6Uuca8&t=769s) Risk Factors for TB the big things is exposure. When we talk about risk factors for exposure, it's really how you I would say how you get the bacteria. And so this is basically into the lungs. That's really what it comes down to. It's how you get the bacteria. Now, when we talk about this, how do you actually get it? Well, it's via respiratory droplets. And so whenever a person is nearby somebody else who has maybe mcoacterium tuberculosis and they cough, they sneeze and that respiratory droplets move into the lungs, they find an opportunity to get down here and start causing some potential damage. If the person's immune system, for whatever reason, doesn't have the capability of being able to fight back. So how this thing gets in is via the processes called respiratory droplets. So, you have to be relatively close to someone who probably has TB or has a very high risk, you know, scenario of potentially having TB. So, we're spreading this bad boy via respiratory droplets. How would I actually really increase my risk of getting the bacteria? Well, one is high prevalent areas. So, I would call this more specifically endemic exposure. It's endemic exposure. So what areas have a high kind of prevalence of tuberculosis? Asia, Africa, probably even like Latin America as well if we wanted to add that one in there as well. So here we'll actually we'll throw that one in there too. Latin America. So again, it's more particularly those who were kind of born into these particular areas or traveled to those areas. That's an exposure risk. The other thing is going to be some type of like close contact exposure. Um and so what do I mean by this? This is could be a family member. This could be a friend, but it's someone who you were around and they had active TV. This is a pretty high-risisk component. So again, endemic exposure really, really important, especially for your exams. Um, but I'd say the close contact one is just anybody. This doesn't really matter, but this is like again it is the most likely one to have that highest risk of kind of inoculation. So close contact exposure was someone again it has to be it's someone who has active TB. All right. The other component here is going to be probably higher risk kind of areas. Um, and so what do I mean by this? The last one I would say is just going to be kind of like overall high-risk regions or high-risk kind of like workplaces, facilities. So high-risk areas. Um, and so the ones that I would want you guys to think about for this one is probably going to be like the hospitals. So, anybody who's in the health care kind of like aspect probably going to is going to have some degree of risk here. So, health care would probably be a big one. Um, another one I would definitely want to think about is potentially like homeless shelters. That is a potential risk factor as well. So, the homeless shelters and we could even go down the line and sometimes they even include in like prisons if you really want. We could even add in like prisons as well. But I think the biggest ones that I would want you guys to remember is probably going to be a close contact exposure or some type of like especially for the exams because it's a perfect vignette to set you up. They just came back from traveling or they were born in some area of Asia, Africa. So they had that exposure risk. All right. So the first thing is they get the bacteria in. The second component is we have to then determine okay is a person they got the bacteria in. Are they having a primary infection that progresses right that progresses or goes dormant and then in certain scenarios it reactivates and that's really kind of the step here that's critical. So you have a person who gets a primary infection. Either they progress and they continue to have active disease or they get a primary infection, it goes dormant and then it reactivates. So let me explain something for a second. In most patients, I'd probably say greater than n g greater than equal to 90% of cases, they go to a stage called latent. So in other words, this means that they have latent TB. latent TB means that they don't really have an active infection. What kind of happens here in just a simplistic way because I'm going to go into detail more there in a second is they get the bacteria in. So here's the bacteria. Then what happens is if you have a good enough immune system, your immune system's capable, it's functioning in the normal individual, you'll wall this thing off. And when you wall it off, it kind of goes into this dormant state where it's still there. It's actually present in your lungs. you maybe didn't completely eradicate it, but you walled it off and so it's in this sleepy state. That's called latent TB. In about probably whatever the remaining portion of this is, so less than 10% of cases, they can progress. So in other words, you get this kind of infection, the pathogens get here, maybe you try your best to kind of wall it off, but it doesn't really do a great job because your immune system isn't as strong. And because of that, it spreads to a bunch of different areas. And maybe it spreads throughout the lungs. Maybe this even gets into the bloodstream. It gets into your lymphatics. And this thing starts to kind of go haywire because you just don't have maybe that proper immune system to wall this thing off. And so because of that, this thing spread throughout the lungs or it spread to the bloodstream and it became disseminated. In this scenario, we call this primary progressive TB. So, primary progressive TB. All right? So, that is the first thing that I want you guys to remember is again most of the patients if they have a good enough immune system, they go into a state of dormcancy. Some of those patients who just don't have a robust immune system, they're probably in some way, shape, or form immunosuppressed, and we'll get into that. They can't kind of wall this bacteria off. And so because of that it can kind of spread spread even get into the bloodstream and start to disseminate. In another scenario out of this patients that most often go into latency in certain scenarios sometimes you have something that pushes the individual to where they had it walled off but then what happened is it decided to maybe come out of dormcancy. And I'll get into how this actually happens, but whenever they're in these areas, especially reactivation, reactivation typically likes to occur in the upper lobes of the lungs. Why? Remember I told you that this is an area of high oxygen tension. And so what we'll notice in patients who get reactivation TB is they end up getting kind of this liquefactive necrosis that occurs in the apex of the lungs. And that my friend is called reactivation TB. All right? So this is called reactivation. Some even call it post primary. So reactivation TB or post primary TB in case you hear that. So what I want you to get at is you get exposure to the bacteria, gets its way into the lungs. If it gets into the lungs, it can either do one of two things. It can progress if you just don't have the robust immune system or you can go into a dormant state. But in certain scenarios, you can reactivate it. The question becomes not as much here. It can be a certain degree of a question, but I'd say a lot of it comes in here. What's really the reason why they come out of latency and go into this reactivation state? And often times it comes down to a suppressed immune system. So, one of them is that you have a really diminished activity. And I promise you'll see what I mean by this a little bit later is you have a reduced activity of your tea cells. And particularly it's called your TH cells. Your technically these T- helpper cells are CD4 cells. That's really what we're going to call them. They're CD4 cells. And what is really critical about our CD4 cells which are going to represent here is that they help to secrete a bunch of different types of cytoines that are really helpful for this TB. one that they release is really critical and what it does is it really kind of activates macrofasages makes them really just beasties and try to really focus on killing and destroying these microbacterium. It makes them a little bit more hearty. All right, that chemical that they release is called interferon gamma. All right, interferon gamma activates macrofasages and then what macrofasages do is they also pump out a particular cytoine to activate more tea cells bring in more macrofasages and that's called TNF alpha but TNF alpha is not only released by in this case the macrofase it's also released by these te- cells and what happens is in all of this is that te- cells really whenever they get hit with interferon gamma It activates macrofasages. Macrofasages release TNF alpha. T- cells release TNF alpha. What does this do? Brings more macrofasages to the area. All this is trying to do is if I bring all of these immune system cells to the area, theoretically I should be strong enough to take this bacteria and push it into the jail. Put it into the prison. And I'll explain what that prison is over in the pathophysiology. For right now, what I want you to trust about this is that really what we're trying to make is this prison is what we're going to refer to as a granuloma for right now. So, for right now, I just want you to trust me that this is what we're going to eventually push them into is a granuloma. All right? But we need sufficient amount of tea cells and these like inflammatory cytoines. So what if I don't have te- cells and what if I have a reduction in these cytoines and the inflammatory cytoines I'd say the most important one is going to be what? Well it definitely is interferon gamma but I'd say TNF alpha is probably going to be the biggest one that I want you guys to associate with this. So what conditions really reduces your te- cells? Come on think about it. If I have a condition called HIV or AIDS, what does that do to my te- cell levels? It drops them. So in patients who have HIV AIDS, you drop their T- cell levels. If levels, they don't make as much of the interferon gamma. Can they stimulate the macrofasages? No. If they can't, they inhibit the macrofasages. Do they release TNF alpha? No. Because of that, do you put them into the prison? No. And so what ends up happening is unfortunately these little suckers escape and they grow and they grow and this is basically what pushes the bacteria to grow and cause more damage and that's what we don't want right so out of this you're getting more of this bacterial growth. If I have patients who have really low levels of these cytoines what would be a reason for this happening? Well, I think the biggest one is any kind of amunosuppressant. That's really the case is any amunosuppressant drug is probably going to be a pretty strong trigger here. So, we'll write this one out. So, this is really any kind of amunosuppressants. And again, I'll give you guys a couple examples of these, but I think the most common one that I would want you guys to think about for the exam is what type of drug? A TNF alpha inhibitor. So steroids, transplant rejection meds, TNF alpha inhibitors, which we use in a lot of different types of conditions, especially things like inflammatory bowel disease. We use it in a lot of like rheumatic diseases. So these are things that we really want to consider. If you drive down their kind of overall immune response, you don't keep them in these granulomaas. And so if we can't keep them in the granulomaas, either they progress, right? That's one of the other concept here is that again same it's kind of a similar concept here they don't put them in the granulomaas or they don't maintain the granulomaas they break free and when they break free their predilction is for what area for the apex of the lungs and then for the primary progressive it's usually middle and lower lobe which I promise we'll get into so again what I want you to understand here is when a person gets exposed to something like mcoacterium tuberculosis the exposure is getting the bacteria In the reason why it even becomes active, which is either primary progressive or reactivation, is you have to have something that's suppressing the immune response. HIV AIDS dropping your tea cells or immunosuppressants shutting down the cytoine response. That could be steroids, that could be transplant rejection meds, that could even be TNF alpha inhibitors. HIV AIDS is probably going to be one of the highest risk, probably about 50fold increased risk in tuberculosis with HIV AIDS. All right, that's the big thing. Now, if you have a good immune system, you're going to probably be fine and you're going to go into a dormcancy state and you don't have to potentially worry about this. And now, these are the biggest risk factors for why this happens, but it could be a lot of other mild ones. I just wanted to give you the most probably extreme ones, but you can see this in patients who just have we can see these in patients who are just malnourished, acutely ill, periods of just overall physical stress. This can also drive this process. All right. So with that being said, we talked about the particular pathogen which is mcoacterium tuberculosis. We talked a lot about the risk factors for getting exposed and we talked about the risk factors that actually cause it to progress. What I need to do now, which is going to take a little bit of time, but I want you guys to stick with me, is ### [27:01](https://www.youtube.com/watch?v=Qjo9F6Uuca8&t=1621s) Pathophysiology of TB to go through once the moment this microacterium hits the alvoli, how does it cause these granulomaas, which is going to be, you know, a hefty discussion, but let's kind of dig into it. All right, so first thing is how do they spread again? Respiratory droplets. So there is some type of movement of these pathogens and basically they are going to be spread via respiratory droplets from a close contact exposure from being in an endemic population from being in a high-risisk area. Either way these things make their way into the lungs. I told you a little bit about what's the most common locations. I'm going to recap that again. Often times these prefer to start off their initial infectious kind of process really in the lower loes and in the middle lobes. And again it could be the right or the left but again usually there's only a middle lobe on the right. All right? But it could be it's usually more in the middle lower loes. So that's the first thing I want you to remember is initial location is oftent times it's going to be middle lobes or lower loes. But there's another component that I have to add on to that. So first thing is often times the initial location where it's going to start all of its kind of process is middle or lower loes. But the other thing is look how close it is to this pink tissue that I'm going to draw here. So we have a piece of kind of a pink tissue here. This is the visceral plura. And then what's this one here called? That's called the parietal plura. It's just beneath the visceral plura. So we call that a subplural type of location, right? So it's middle lower lobe and it's usually subplural. All right, we have a location of where these initially start once you get an exposure. Now once they get in there, guess what? Macrofasages say, "Hold my beer. I got you. I'm going to help you out a little bit here, bear, buddy. " So what happens is the macrofasages are going to be a part of your innate immune response. And what they're going to do is they're going to see these mcoacterium and they're going to undergo a process which I told you guys which is going to be where they eat them. They undergo the eating of them. They bring them inside of them. And what's that called? This is called fagoscytosis. So the first step is going to be something called fagago cytosis. And that's going to take it inside and it's going to bring it inside of this little thing called a fagosome which is going to be right there. And again what's going to be inside of it? It's going to be the mcoacterium tuberculosis. Then what happens is this son of a gun, we already told you it's supposed to fuse. What is it supposed to fuse with? Well, then you have your fagosome and it's supposed to combine with something called a lo, right? So here's our lo and this is going to have all the looal enzymes. This fagosome is going to contain the mcoacterium tuberculosis. And what is it supposed to undergo? it's supposed to undergo fusion. So then we should have something called fusion. So here we have again the fagosome which is basically the macrofase that contains the TB. Then after that we're going to have fusion of the fagaloo. Well we should fagaloome. So at this step we should have fagago lysosome fusion which is going to be at this step right here. So the first process was fagocytosis. The second process is going to be fagalizosome fusion. I told you though that there was something that happens at this step. We have something inside of the mcoacterium species that prevents this. Do you guys remember what it was that inhibits this process? I'll give you a hint. It started with an S. It was called the sulfatides. Yeah. So the miccoacterium has something called sulfatides. And the sulfatides are pretty much a virilence factor that what it's going to do is it's going to inhibit this fagago loome fusion. That's what it's going to do. So instead of these guys going and actually fusing together, what happens? We're going to inhibit that process. this fusion. And so now what happens is these were supposed to come together, but they don't. And so we kind of keep this unfortunately the fagosome never fuses. And so we're still stuck with this guy over here containing all of that TB and we're still unfortunately stuck with this loss over here which aren't able to fuse. What happens is this bacteria, it's not really undergoing destruction. So because of that, guess what it decides to do? It decides to replicate in the macrofase. So that's the next step. So the first thing was fagocytosis. Second thing is once we actually have the fagosome is to fuse it with the fagaloome. All right? To actually loome to make a fagosome. So these were supposed to come together, right? We're supposed to have the fusion of these two. And again, it's going to be the what two things? It's the fagago fagosome. Actually, put this here. It's supposed to be the fusion of the fagosome and the lysosome. We're supposed to bring these together, but we're not going to. Because of that, all you end up having here is just bacteria that are going to replicate in the macroofase. These things are going to just replicate like bunnies. Because of that, now we get this infected macrofase. So now I have this infected macrofase and what does it have all the way filled inside of it? It's got all these mcoacterium species just growing within it. So again what is this here called? This is called a infected this is called an infected alvolar macrofase. Now that's the first thing that I want you guys to remember in this step. So the first component here that happened is that you had inhalation via respiratory droplets gets into the airway causes its initial kind of sight of infection which is middle lower lobe. It's usually subpl. If we zoom in into the alvoli macrofasages are supposed to undergo fagocytosis that actually does occur. They get a fagosome. You're supposed to combine the fagosome and the loome to make a fagosome. But guess what the sulfatide does? The sulfatide inhibits that fusion. So now that never happens and then you just have all of these bacteria that replicate in the micro macrofase. Now I got an infected macroofase. It's incapable of doing its job. So what does it need? It's got to call out onto its friend. So what happens is the infected macrofase releases a couple different cytoines. It releases things like interlucan one. TNF alpha. And that's going to get pumped out from this alvoli, which is where all of this process is occurring. It's going to get into the blood or lymphatic circulation. Once it does that, these cytoines are going to go and activate different types of immune system cells, right? And generally the way I want you to think about them is just overall antigen presenting cells. And we're going to try to activate these antigen presenting cells. What are the two antigen presenting cells that I really want you guys to remember in this scenario? The two antigen presenting cells is going to be the dendritic cells. That's going to be kind of the heavy hitters in this scenario and then again it's going to be monocytes that come to the area and generally turn into macrofasages. So these are the two ones that I want you to think about. But the heavy hitter in this scenario is going to be the dendritic cells. So they're going to come from the lymph, blood and they're going to come to this area. All right? So we're going to activate those puppies. And again, who's really helping with it? It's these high levels of things like interlucan one and tumor necrotic factor alpha that's being released by the infected macrofasages. Once that happens these dendritic cells here's our antigen presenting cell. We're just going to use this. This is our antigen presenting cell. All right here is the mcoacterium tuberculosis. It undergoes fagocytosis. So once it under goes fagocytosis inside of this dendritic cell basically what happens is it will take some pieces of it and expose it on its MHC2 complex. When it exposes it on the MHC2 complex you're supposed to have this interaction here which is the MHC2 complex with your T- cell receptor. These interact basically once you get this connection you have generally a co-stimulatory signal and this thing is ready to roll. what's ready to roll. This is a naive tea cell, which means it doesn't really it's not kind of it doesn't know what its job is meant to be. It doesn't know if it's meant to be a T-H helpper cell, a cytotoxic tea cell. It doesn't even know what kind of T- helpper cell it needs to be. So what happens is the macroofage is smart and some other cytoines that get released here is not just interlucan one and tumor necrotic factor alpha. So let's actually kind of show that these are the cytoines first and then we'll bring these over here. But another cytoine that's also getting kind of pumped out here and causes some pretty uh helpful scenarios here is called interlucan 12. So that's another site that kind of gets released. So it's interlucan one TNF alpha and interlucan 12. Once the dendritic cell undergoes this fagocytosis, takes a piece of that mcoacterium and exposes it on side of its membrane, activates this interaction, then interlucan 12 comes in and really drives this naive tea cell to have an actual determination of what it's going to be. And so what it does is it says, "All right, folks. I know what I'm meant to be when I grow up. " and it turns into a very specific type of TE-C cell that underos an excessive amount of proliferation and this is called T-helper one cells and that's where these are becoming the big dogs the macrofase it just couldn't handle the it couldn't handle the heat and so what ends up happening is with this interaction with the antigen presenting cells and the interlucan 12 this naive T- cell it became TH1 cells I already told you they release a very heavy amount of a very specific type of cytoine. Do you guys remember what that one is? It's called interferon gamma. Interferon gamma is the big cytoine in this scenario that is going to help us to drive a particular type of immune response. One of those immune responses is it's going to tell this macrofase to become better. It says just come on bro, level up your game. And so the macrofase kind of goes from being like a fagocitic type of factory where it kind of eats things to where it becomes really good at releasing things like reactive oxygen species and proteasis and tries to undergo a lot of intracellular killing. All of this is really trying to put this bacteria into dormcy. So one of the things that it does is it stimulates a lot of what's called intracellular killing by the macrofase. It basically just makes it like a beast. Makes it kind of like a little bit more of a enhanced activated macrofase. So it under goes intracellular killing and that's one thing that it does to this macroofage is it really amps up its activity to be able to kill the pathogen. The other thing here is it tells these macrofasages to start to undergo this kind of conversion and transformation process. And so it drives process if you will where a bunch of these macrofasages kind of come together and fuse and it becomes one big giant cell. That's what we call them. We call them giant cells. So we actually call them Langghans giant cells. So Langghan giant cells. Some of them actually make what's called epithelioid hyocites. But I don't want you guys to go too crazy on that. I just want you to know that what we make is we stimulate the formation of these things called langghan giant cells. It's basically I'm not kidding just a bunch of macrofasages that are fused together and they may contain some of the mcoacterial tuberculosis in them. And what else is actually happening? interferon gamma not only is helping convert them but it's making them good at killing all of this is supposed to basically do two things one is to help the macrofasages be better at killing the pathogen and also start to kind of like wall this off this big cell becomes like a wall it's trying to keep the TV in one particular place not letting it spread around that's one of the benefits of this so in this scenario we started off we got the exposure That thing got into the lungs. It interacted with the macrofase. Macrofase couldn't handle it. Says, "Let me tell my buddies. " Tells antigen presenting cells. They come in. They help with fagosytosing them, presenting them to naive tea cells. And we turn this into a T-helper one cell. These things go ham and start pumping out interferon gamma. When they do that, activates the macrofasages, causes them to convert into big giant cells. We start kind of killing the pathogen and making a wall. So, let's talk about what that wall is. That wall, if you will, is called a granuloma. Now, this is what's really interesting. We're having the granuloma, which we're kind of just zooming in on here. It's really in this alvoli. It's where is it again? I told you usually middle, lower lobe, and subplural. If I zoom in on this and how all of this is happening in kind of a really cool sequence from the most outer part of this granuloma is what? Well, the first one is the orange cells. These are called your T-H helpper one cells. What are the job of the T-helper one cells? Well, think about it. This thing is on the outside and it's just spewing out what type of cytoine to tell the Lang Hans giant cells to tell the macrofasages to be good at their job. What is that? Interferon gamma. So, it's just pumping out interferon gamma to feed what? The inner core. It's feeding the inner core of macrofasages and giant cells. All right. Then we get into the second component. What's that? Well, technically it's going to be the kind of the outer wall which is all those macrofasages that fuse together. Some of them are epithelioid hysteocytes and a lot of them are lang giant cells. So that's the second part here is the lang hans giant cells. And again, I would even add in there if you guys want that these are also going to contain the epithelioid hysteocytes. These are basically a um basically I'd say a group of macrofasages that are fused and they're kind of helping to contain some of this pathogen. That's really their job. It's a bunch of them that help to contain that particular pathogen. And in the inner kind of core is the macrofasages. Now some of these obviously could be infected, some of them may not be infected. So but again I think the important thing is that a lot of these are the ones that are really undergoing a lot of the killing process and some of them will contain the pathogen inside of them and even some of the Langhans giant cells may contain some of the pathogen inside of them. But the big component here is that we're containing it in this outer rim of tea cells. So again macrofasages are cool because they're supposed to do two things in this scenario. One is they're supposed to kill, but they're also they're really important to maintain this granuloma. And so they do two things. One is they kill the mcoacterium tuberculosis. The second thing is that they really pump out tons of something called TNF alpha. So that's another really important thing that I want you guys to understand. We made the granuloma which was the macrofase fagocytosed the mcoacterium couldn't really kill it told te- cells hey te- cells I need the t-helper one cells to come over here t- helpper one cells come over they activate the macrofasages make them better eating more of them then they have some of the macrofase turned into giant cells and come around them and then we end up with this kind of like nice little circular structure here that's containing a bunch of different types of cells now interferon gamma is keeping the wall in place. Tumor necrotic factor alpha is really critical though. Let me explain why the tumor necrotic factor alpha there's released from actually here let's just let's zoom in it from outside here. When we take these cells here the tea cells they do also release TNF alpha but the macrofasages are really that heavy source of TNF alpha. And so what happens is the TNF alpha is really cool because what it's trying to do is to keep more monocytes right which will come to the area and turn into macrofasages to keep the lymphosytes coming to the area and keep reinforcing that granuloma. So these are supposed to do that they're supposed to pump out things like TNF alpha to help to stimulate the macroofasages to come to the area to help to stimulate the tea cells to come to the area. Right? That's what we want. And because if they come to the area, we're going to reinforce and maintain the granuloma. I told you if you give someone TNF alpha inhibitors, you shut down that TNF alpha. TNF alpha is really critical for maintaining the granuloma. These tea cells around the outer core are keeping the granuloma also in place with interferon gamma. So the maintenance of the granuloma is really primarily maintained by TNF alpha and T-C cells secretreting interferon gamma to keep the macrofasages intact. All right. What happens is when you have all of these cells clumped up together is oxygen requirements go up. So your tissue starts to become hypoxic. So the center core center of the granuloma experiences under goes hypoxia. That's one event that actually starts to take place. There's a bunch of different cells here, a lot of cells, not enough oxygen to go around. And so the most susceptible area, which is the center portion of it, under goes hypoxia. That's one component here. All right. The second component here is that the macrofasages, they are releasing tons of reactive oxygen species, tons of proteasis. So there's going to be lots of reactive oxygen species and proteiases that are released by the macrofasages and attempt to kill the mcoacterium, right? And so there's lots of reactive oxygen species, lots of proteiases. And what that is designed to do is to kill the mcoacterium. But this stuff isn't selective. It says I'll damage whatever I have around me. And what it does is since you have hypoxia to the center and all these reactive oxygen species, it causes tissue necrosis in the center. And so the combination of these things lead to a tissue necrosis in the center. And that tissue necrosis starts to kind of look like it has it's like looks like a bunch of cheese like with holes in it like Swiss cheese. And we call this case necrosis. So it's technically called cacius necrosis. And when that happens, all of this center, which will represent, we'll do it here. We'll just do it in this kind of um let's just use the black actually. All of this, all of this is the case core. That is going to be the inner center gooey portion that contains all of that dead tissue. All right, that's the tissue necrosis. So what we give this kind of thing is it's technically a granuloma but it's got a necrotic case core. So what do we call this thing? Technically this thing is called a caseiating. It's called a caseiating granuloma. And again if somebody were to say hey Zach what's a granuloma again? It's an outer core of T- cells. Technically this would be your T-H helpper one cells. Then you're going to have your Langhans giant macrofasages, right? And again, in the inner center of it, you're going to have some necrotic debris. Why? Because a bunch of the cells in the center start to undergo hypoxy because there's too much cells, not enough oxygen delivery. And on top of that, reactive oxygen species and proteasis that are being released by macrofasages cause a lot of innocent bystander destruction and all of that inner destructive tissue. Actually, we'll do a different color. Let's do for right now. Let's do kind of a pinkish color for right now because all the pink I want to represent like dead cells. This is like dead macrofasages. This could be some dead J uh um Langhan's giant cells. But what's in the inner center of it? the actual mcoacterium that's kind of in this cheesy center that is really the inner center goo which is going to be containing dead cells inflammatory exidate and the mcoacterial species. But the beautiful thing about a caseating granuloma is I want you to think about this as the TB prison. This is essentially going to be my TB prison. And if I have a proper immune system, I should be able to contain these things in that middle lower lobe portion of the lung just beneath the plura. If I don't have the immune system capable, it could then progress. If it goes into latency, it could potentially reactivate. So now let's go into the next step here. The next component is we've done a pretty good job at forming these caseing granulomaas. And again, it's really important to remember where is this? So what's this portion here? I'm just going to use the outer portion of the lung. We're going to call this the subplural portion. And it's going to be in the middle lower lobe. And again, it's going to have that outer core, which is the T-C cells. And it's going to have that inner kind of uh portion with the laying on giant cells. And it's going to have all this case necrotic material. There's our caseating granuloma. Right? Here's the thing. There's all these lymph nodes that are in the hilum. This is connected, dude. So you got to remember there's lymphatic system channels that exist here and this can drain into this lymph node. And so all of these microbacterial species they had the opportunity to potentially spread over here and cause that same kind of concept over here in the higher lymph nodes. And so whenever they do that you get the same thing which will have the outer T- cell core then you'll have the Langhan giant cells and you'll have some macrofasages but a lot of dead cellular debris containing the mcoacterium. All right. Now when this happens you have two components here. One is you have the caseing granuloma at this portion of the lung and you have a case seating granuloma here at the lymph node. These are two different components here. So the first thing is we have something called a gone focus. So what is a gon focus? The gon focus is one that's basically a caseiating granuloma that is usually near the middle lower lobe of the lung and it's a subplural structure. So that's the first thing that's going to be this part. All right. The second one is the hily node. So you have case eating granulomaomas that form within the hily node and makes it bigger and so that causes hiler lympadinopathy. Now the combination of these two gives you something called a gone complex that is the next component here. So we have a gone complex. So a gone complex is essentially a gone focus which is a caseing granuloma at the subplural portion of the middle lower lobes of the lungs and hyolympinopathy which is due to caseing granulomaomas within the hily node. That's a gone complex. Now a gong complex can pretty much you're at this point these bacteria are pretty much dormant. They're kind of in a sleepy state. They're not killed. they're still there. What happens though is that we try to show that this area of the lung healed and when it does that it kind of under goes some fibrosis and we call this when it under goes fibrosis and calcification of the gong complex we call that a ranky complex. So what is a ranky complex? It's essentially I mean honestly the simplest way of defining this is essentially this is a fibroalcification process. That's all it is. It's that the gong complex under goes fibro calcification. So let's example that. Here we're going to have the gon focus. Here we'll have a caseing granuloma right there. again T-C cells outer core laying on giant cells and then the inner kind of portion which contains all of that dead cheesy necrotic material is the caseating portion and then what happens is it under goes fibrosis what color should we represent with let's do this kind of bluish color here so now it under goes some fibroalcification so now all of this under goes fibro calcification in these areas that is called a ranky complex And pretty much this thing is at a point of where we would consider it pretty much like healed. So it's kind of like a healed up gone complex. There's another thing that's really interesting. These gone complexes, again, this is technically dormant. This is technically a healed dormant spot. There's another kind of thing that happens. And I actually found this super interesting because I always wondered whenever a TB reactivates, why does it how does it end up reactivating in the upper lobe of the lung? I just couldn't figure that out. like how does it actually get there? And so it does travel, but it had to be there even before you undergo the reactivation process. And so what's kind of cool here is you have here I'm going to say that this is our gone focus outer ring of tea cells langhan giant cells and for right now what I'm going to do is I'm going to have some purple which is again our mcoacterium. this mcoacterium, a lot of them before they just get ready to go into this dormcancy state, some of them kind of hitch a ride via the bloodstream and they lymphatic system and they go to other areas of the body where they can also go and lay dormant. They can go to the kidneys, brain, they can go to the heart, they can go all over the dang place. But this is before, right before they go into this dormcy state. One of the areas that it also loves to go to before it kind of decides to go to bed is into the apex of the lungs. So it uses the bloodstream, it uses the lymphatic channels to get to the upper lobes of the lungs. And then essentially what happens is they make these like tiny little like fosi. It's almost like a gone focus, but it's so tiny that you can barely see it on something like a chest X-ray, but you do get kind of like a little granulomous formation here. There's formation. So we started off with a gone focus right here. This is our gone focus and then what happened is it spread up here to the apex of the lungs via the lymph in the blood. This is called lymphohhematogenous seeding. This is called a simon focus. Let's actually write that down. And that simon focus is basically some of the mcoacterium tuberculosis that traveled from the subplural middle lower lobe case granuloma to the apex and it goes into a dormcancy state. That's all this is my friends. So we have here a simon focus. So again a ranky complex is basically fibroalcification of the gone complex. A gong complex that then breaks off and gives these small little like microscopic caseing granulomaas to the apex of the lungs before it goes into dormcy. Simon focus gone focus just that subplur portion of that case granuloma. Hilyinopathy is due to swelling that occurs in the hilymph node due to a case granuloma there. Wow. All right. So at this point we have become infected. The innate response with your macrofasages couldn't handle it. Who' they call in? They call the TH1 cells. TH1 cells really help to form the granuloma. You got the granuloma. Where do they like to form? In the middle lower lobe of the lung. Usually near the plura. When it underos that kind of process it, it can then spread via the lymphatic system and go to what? It can go to nearby lymph nodes. What's the lymph nodes? Hilo lymph nodes. When you get a case granuloma in that portion of the lung plus enlargement of the hily node, we call that a gum complex. This is pretty much is getting ready to go into dormcancy. It's getting ready to be controlled and go to bed. If we undergo fibroalcification, essentially all this means is it's undergone a healing process. And this generally kind of takes some time, but it's basically healed. It's healing. It's a healing up of that gong complex. Some of them will hit your ride via the lymphhematogenous seating process and get to the apex of the lung and create a simon focus. And this becomes really critical. This is critical to reactivation TB because they are hanging out there already. They are ready whenever the opportunity arises. You give them the opportunity, they will take it and they'll start undergoing necrosis and liquefies of that case material in the upper lobe. If you let them reactivate, so we can't let them, but that's what will happen. All right, let's now take the time to talk about when a person gets infected, we undergo the exposure, we go through all of this immune response. How do I really know if it's latent? primary progressive? How do I really know if it's reactivation TB? not just the process of it but how do I truly understand them based upon the whole immune response and which one's causing lung tissue destruction which one's ### [57:52](https://www.youtube.com/watch?v=Qjo9F6Uuca8&t=3472s) Latent vs. Active TB going to have an abnormal kind of chest X-ray etc let's do that all right so we started off here and we said again what happened here we had a person they get an exposure they undergo the immune response innate then they go through the adaptive which is the TH1 then from there we create granulomaas and generally these granulomaas are caseating and again they often times will form where initi Initially they'll form in this kind of middle lower lobe of the lung right that's where we said and then again it can also form here in the hiler lymph nodes right and I think the critical thing to remember here is again how do we kind of define this was technically in this scenario this was called that gone complex right now in most individuals we said what percentage probably greater than 90% greater than or equal to 90% they go into this latent state. All this means is that we were able to contain the TB. All right? So essentially what that means is you contained this. You had the proper immune response and whenever this happened, you were able to pretty much keep these kind of pathogens snoozing, if you will. So you kept them in the dormant state. You basically prevented them from constantly undergoing replication. So they're there but they're not actively doing any kind of problems and damage. All right. So you c you created these case granulomomas in these areas and maybe they even underwent fibrocalification and healed up. But in this scenario you have an individual who these bacteria are dormant but they're not replicating and causing tissue destruction. That's the key here. So latent TB, you got a good immune response. You go this way. You go into this dormant state. That's what I want you to remember. This is basically is the microacterium tuberculosis are dormant. They're there. They're not growing. They're not undergoing any tissue destruction, but they are there. The person does have the TB bacteria there. All right. In less than or equal to actually I would say less than generally in less than 10% of cases if you just don't have that proper immune response right to be able to contain or to form these granulomaas they may not completely be maintained. So if you don't have the T-C cells that are able to keep that interferon gamma coming, you don't have the uh tumor necrotic factor alpha that's present for macrofasages because you're suppressing it in some way, shape or form. In those scenarios, you can't maintain the granulos. Here's what I want you to think about. Here's the granuloma, but we can't any longer keep it formed. And so because of that, all this mcoacterium basically starts to grow. And when it grows, it again can grow within this particular portion of where it started its infection, which is usually like the middle, maybe even the lower loes. Again, middle lower loes. So what happened here is you had the case granuloma, but you couldn't contain it anymore. You couldn't maintain it. It bust out. The bacteria start causing further destruction. At that point, this is called primary progressive TV. So again, what's this one called? This is called primary progressive TB. You just basically you couldn't contain it. So in this scenario, the mcoacterium tuberculosis are active and the mcoacterium tuberculosis is causing damage to the lung tissue. And usually what's interesting about this is that when we think about these like pathogens, they often times in this primary progressive one, they can kind of form like consolidations, basically kind of just damaged areas of fluid um exidate a lot of different types of immune system cells and dead tissue. It kind of accumulates within the alvoli and the bronchioles and it forms kind of like this consolidation, if you will. And so that's one thing that's really kind of unique about primary progressive TB is it's more of a middle a lower lobe consolidation. And so sometimes we'll get into this is this can kind of mimic like a pneumonia. It's almost like an atypical pneumonia person who just keeps getting treated with antibiotics and they're just not getting better over recurrently. At least three more times they've been treated for this pneumonia and they're just not getting any better. and you get a chest X-ray and they still have this consolidation that's present in a particular lobe of the lung middle lower loes that is pretty much consistent with that primary progressive TV and especially if they have the what else up here the hiler lympadinopathy because again the bacteria will also not be able to be contained here and it'll grow and potentially cause some enlargement within the lymph nodes. All right. Well, that's one thing. this patient you went this way because you just didn't have the immune response. This way you had the immune response but at some point you lost your immune response. Maybe again person decided to get HIV AIDS. Maybe the person decided to take an imunosuppressant like TNF alpha inhibitor. They took a steroid. They got a transplant. They're on transplant rejection meds. They got acutely ill. Whatever it happened their immune system activity dropped. Their TNF alpha dropped. Their interferon gamma dropped. or T-C cell level activity dropped and they no longer could contain these granulomaas. But remember, I told you that there's a specific place for reactivation TB. What I want you to remember is that it's usually in these upper lobes. And so what happens is you had these kind of like little focus. What were they called? Come on. I want you guys to remember, don't you dare say a gone focus. It was a simon focus and they could have a couple of these in the upper lobes of the lung. They had the mcoacterium tuberculosis that was there. What happens is you lose the immune activity. All right, you lose the TNF alpha, you lose that interferent gamma. macrofasages go into like this weird destructive state and they start releasing a bunch of like proteases, metalloprotein aces and all they basically do is they destroy all of that case material that was in there. There was some case and granulomaas even in the dormant state and what happens is it gets filled with all of this necrotic liquid material. So all we're going to do is we're going to liquefy the case necrotic material in these granulomaas. Now we end up with these. Here's what happens. They get close to a bronchi. And these things are like I mean I'm not kidding. This is necrotic material. Imagine like basically like hydrochloric acid. They get close to the airway and they start eating their way in to the airway. And then this bacteria that's all in this kind of liquefied broth, if you really want to think about it like that, can easily spread via the bronchi all over the dang lungs. And then on top of that, if they decide to cough and they cough up that debris, it basically gets rid of all of that debris that's in these kind of like liquidified cavities, if you will. And so now all of that moved. They coughed all of that up. that allows for them to be extremely potentially contagious. But what it did is it left these cavities present in the upper lobes of the lungs and these cavities which are a mixture of again liquefied necrotic debris and fibrous tissue. These are called fibroacius cavities. And so that's really what's key about this one. And this is called reactivation TB. So reactivation TB the classic thing for this one is cavitary lesions in the upper lobes. That's what I want you to remember differentiating these two from each other is again cavitary lesions where in the apex. Why the apex? Because it's the highest level of oxygen tension. That's where they're going to thrive. grow. That's where they're going to cause tons and tons of destruction. So that's one of the big differences between these two. And again, the same concept exists here. These mcoacterium species, they're all mixed into that liquid like necrotic broth if you want to think about it. So when we think about the TB here, it's the same thing. They are extremely active. So they have their mcoacterium tuberculosis is active and the microacterium tuberculosis is causing what did I write here? Causing damage. Yeah, same exact thing. It's leading to a point which I'm going to make here in just a second. All right. So, they're still causing damage and they are still active in this scenario. Here's the thing with these two. They'll basically keep kind of spreading throughout the lungs. This will keep So, you're going to get from this progressive lung damage. that progressive lung damage that you'll get from both of these we see as the form of pulmonary TB which again this can look a lot of different ways from both of them obviously in this person they may have some kind of findings of uh pneumonia presentation maybe they have a prolonged fever night sweats chills cough they have a chest X-ray that shows a consolidate that doesn't go away reactivation TB and this one they can have pulmonary TB symptoms maybe they have a very productive cough Maybe they have some weird amorphic breath sounds. They also have fever. They also have night sweats and chills and weight loss. Again, that's the result of the pulmonary destruction. The other problem here is that these can also spread wear. These pathogens can get into the bloodstream. So that's what we get worried about with these is that if these pathogens they get their way here they are let's say and they get their way in to the lymphatic system or they get out here and they get their way into the circulation that's kind of a pretty terrible issue. So if these pathogens decide to spread, get into the circulation, they decide to go into the lymphatic circulation, where can they go? Well, from here they can go all over the dang place. When that happens, we call this extra pulmonary TB. So this is basically it's using the blood and the lymph as a highway to go and spread to other organs besides the lungs. So this is called extra pulmonary TB. So when a person has active TB really what we call active TB is where the miccoacterium is active. It's reactivation TB and primary progressive TB and it can exist in a pulmonary TB form which is the result of the lung damage or it can exist in extra pulmonary TB where they go to different organs and cause damage in organs besides the lungs. That's really critical here. So I know that this is a lot of stuff and it's probably something where you're like do I really need to know all of this stuff? I think everything is really critical when you're trying to build a foundation. But I think a lot of it can come down to a very simple discussion right here. So when I talk about latent TV, I want you to think about something in both of them. What happened when they both got an infection? exposed, their macroofasages came, they both had a TH1 response. They probably had some degree of interferon gamma that was there. Especially in the latent TB, if they got a good immune system, they should have a normal TH1 response. they should be able to push these guys into forming granulomaas. So in other words, if I were to test the tea cells one day and I were to expose them to that TB antigen, would my tea cells be able to remember that? That's the key between both of them. And if you're exposed, yes, they should both have that memory theoretically, right? So the answer to this is yes. And so the way that we determine that is we do things like positive um we do what's called um positive purified protein derivative or a tuberculine skin test essentially and we inject like 200 different types of microbacterial antigens into the skin and see if the immune system will at least drive those TH1 cells to help to push and make these granulomaas within the skin. All right? And so this should be positive. This should be positive for this patient if they have that exposure. Same thing over here in a perfect world. I'm going to be very careful because I don't want you guys to always assume this. But in a perfect world, if you did the tuberculin skin test and the purified protein derivative and the active TB, it would also be positive because again, they had the exposure. This is about exposure. All right? It doesn't tell you if they have active TB or not. It just tells you, do they have TH cells that if I expose them to that antigen, they would remember it, meaning I had an exposure. The only thing I will say is that you have to watch out for false negatives. We'll talk about this in the diagnostic section, but in individuals who probably have active TV, what's one of the characteristic components here um in TB active TV is they probably have some degree of like an immunosuppression, some degree of it. And so because of that, you can get false negatives if they have an a really deprived immune system. It's called energy. And so we are a little bit more careful of that. But either way, this tells me that they had an exposure. So all this test will tell me is that they had an exposure. What about this? Well, which one did I tell you is their active TB? Well, it's not latent. So if they they're not active, would it cause any types of symptoms and destruction of tissue? No. So there's not going to be there is no destruction. And so all right, here's what I would say. Is there any lung destruction? All right, let's write it like this. No. No lung destruction, right? Is there lung destruction here? Absolutely there is. How would lung destruction look in these patients? One is they could have the presence of symptoms. If there is no lung destruction, there is no symptoms. Theoretically, right? And if there is destruction, theoretically there is going to be symptoms. So that's one difference here. No lung destruction, theoretically you should not have any types of pulmonary TB symptoms or extra pulmonary TB symptoms. Same thing here. If you have lung destruction, you theoretically could have some extra pulmonary or pulmonary TB symptoms. things like fever, cough, night sweats, chills, weight loss, they could have potential pulmonary complications as a result of it. But that's one thing. The other component here is when I get imaging of the chest, would I see anything that would be abnormal that would suggest lung destruction or any kind of damage theoretically for latent TB? Well, Zach, you did say that I could see healed up areas. I'm not asking for healed up areas like a ranky complex or anything like that. I'm saying do I see active disease like a consolidation in the middle lower lobe hiler lymphatinopathy. Do I see any kind of fibroacius cavities in the upper lobe? No. And so generally these should have no abnormal and we're going to just use chest X-ray for right now. Abnormal chest X-ray. There should not be any abnormal chest X-ray. So boom. This one you definitely should have an abnormal chest X-ray. And again, what would it theoretically show? Well, it depends. Are we talking about this as the patient who has something like a primary progressive? They would have that middle lower lobe consolidation. They would have some hilarinopathy. It would kind of look like pneumonia. This one they would have some fibroacius cavities. Theoretically they could even have a pumothorax. This one you can have plural eusions. Absolutely. You can have abnormal chest X-rays, but the big difference here is that they're going to have something abnormal on their imaging that suggests that there is some active destruction. So, this is exposure. This right here is depending upon if they had the immune response capable of containing those granulomaas and forming the granulomaas. If you had the immune system, you'll probably be okay and you'll go into a dormant state. If you don't have the immune response capable of keeping them dormant, they're going to cause some damage. And that's what makes this really critical to understand. All right, let's move on to the last part here which is talking ### [1:14:43](https://www.youtube.com/watch?v=Qjo9F6Uuca8&t=4483s) Clinical Findings and Complications of TB about what are these symptoms? What would they potentially look like? All right. Well, first thing here is pulmonary TB is pretty classic in the sense that the way I would want you guys to think about it is it's kind of like I think about finding TB in the vignettes in two forms. One is a new onset uh hmopysis. That's definitely one way. A second way is probably a person who has a recurrent like progressive pneumonia that's just not getting better with antibiotics. Those are the two ways that I oftent times will see on the exams that they'll test it. But let's dig into this a little bit more. When you have that immune response that's occurring in these areas, I told you that there was macrofasages and there was tea cells getting involved and dude oh dude are they pumping out tons of things like what interlucan one and TNF alpha but the big one here is for shores the TNF alpha. These things are getting pumped out. So all of this is happening where they are just pumping out the TNF alpha the interlucan one. What do we know about these guys? Well, one is that it causes some involvement of systemic kind of in involvement particularly of the hypothalamus and maybe even our muscles. And so what we see is we see this kind of activation of these cytoines here. Let's actually we'll bring it down here. We'll say the first thing here that we see is we see an elevation. We see a lot of cytoines from like interlucan one and TNF alpha. A lot of that systemic kind of involvement here high levels of this. What happens with these is that whenever they get into the bloodstream they go to the hypothalamus activate the hypothalamus. Also TNF alpha is a really powerful um it really helps with a lot of catabolism right um particularly a lot of cexic kind of effects of the actual muscle tissue the lipids. And so we see a lot of cexia or weight loss as a result. So we see a lot of weight loss that occurs and that's usually because of the a lot of the catabolism that is occurring with inside of the muscles and the actual fat tissue. The other thing is that we activate the hypothalamus and the hypothalamus resets our body's thermostat and causes things like fever and night sweats. And so in an individual who comes in with potentially fever and night sweats and an unintentional weight loss, right, and if I threw in cough, you'd probably be like, "Oh, dude, do they have like lung cancer? " That could be another possibility. And you get a chest X-ray and say, "Oh god, there's a weird kind of like lesion there in the lung. " I think the big thing comes down to what was their risk factors for exposure? What was the potential risk factors for potentially progression? But here's another thing. When we talk about this cytoine event, that's one thing that's causing the fever, the night sweats, the weight loss. The second thing is that they most often have a cough and it's probably going to be more of a productive cough. And I think this productive cough is going to be much more likely to be heavily involved in things like the reactivation TB more than something like the uh primary progressive TB. Funny enough, sometimes primary progressive TB can be more asymptomatic than it is symptomatic. That's why we really focus a lot on reactivation TB in your exams. But you definitely can see a productive cough with both of these. You have inflammation. You're going to activate J receptors, cough receptors. They're going to cough. And if they have this consolidation, that's going to come with it. If they erode into an airway, and some of that liquid necrotic debris gets pushed into the bronchios, activates inflammatory and activates J receptors, cough receptors, they cough. You're going to get a productive cough. Right? Extremely common. But I want you to definitely associate this one probably more so with the reactivation probably more than primary progressive. All right. So that's the next part that I want you guys to think about is they have a productive cough, fever, night sweats, weight loss. The next thing here is, and this is why I tell you, if you have a person with a cough, fever, maybe some weight loss over a long period of time, it kind of acts like maybe especially with a cough and a low-grade fever, you think about pneumonia and they get antibiotics because they have a they have an infiltrate on their chest X-ray that shows that and they just don't get better. Another thing that actually is really important to remember is that sometimes if that kind of reactivation TB, that fibroaces cavity erodess and erodess into the bronchial walls. And when it does, it erodess into things like the bronchial arteries or the pulmonary artery branches, it can cause them to bleed into the airway. And so because of that, not only can they cough, they can potentially cough up blood. And he homopsis should hmoptsis should always be on your differential in a patient who presents with TB should always be on the differential in a patient who presents with hmopysis. So homopsis is another potential symptom manifestation. This one I want to tell you about is extremely rare. I think it's not very common but I'm going to tell you it. And this is usually going to be some type of pumo thorax. Usually it's a secondary pumthorax because there's an underlying lung disease here. and it's usually going to have necrosis from those fibroacius cavities that erode into the actual lung wall through the visceral plura and allow for air to escape. So what I want you to do is look at this kind of diagram. I'm just really just zooming in on this particular area. Here's all this liquefied necrotic debris and it's eroding into the bronchial wall eroding here to the alvoli and into the plura. Here we have an opportunity for blood to leak out that causes the hemopysis. And here we create an opportunity or a channel for air to go from the lungs and go into this kind of plural space. And so now we're going to have air kind of leaking into the plural space. So that's another potential thing to think about. So far the big ones are fever, night sweats, weight loss, productive cough, hemopsis. Another thing here is abnormal oscultation. when I go up with my stethoscope and I listen to the patient, it really could be variable. So, what do I mean by that? It's this is not going to be super like helpful to be honest with you because it could sound like they have pneumonia. So, they're going to have some abnormal breath sounds. There is one that we potentially associate with TB. It's called amorphic breath sounds. And essentially the way that uh you could think about it is if you've ever had like um like a Coca-Cola bottle that's empty and you try to blow into it, it's kind of sounds like a hollow kind of sound. That's really what this is. And it's just the sound of air rushing in to the lungs and then moving through that kind of hollow cavity. That's an amorphic breath sound. But other things that you could potentially hear is just you may hear signs of like consolidation. So there could be positive consolidation signs. That means that they could have increased tactile fermitus. They could have dullness to percussion, bronophony, egophony, whispering pectiloquy. They could even have bronchial breast sounds, right? But they're going to have positive signs of lowbar consolidation. Now the thing I want you to remember is with this consolidation about this is that with the consolidation which type of TB would I more like most likely associate this one with? Probably the primary progressive and then the amorphic breast sounds I would associate more with a cavitary lesion which is reactivation TB. So to put it all together, if I had a person who comes in with fever, productive cough, maybe some night sweats, maybe some weight loss, they have ammorphic breath sounds, I might start and especially hmoptus, I'm going to start thinking about the possibility of TB. Now, here's the next component. What if this TB is so vicious that it gains the ability to spread to other places? Maybe it's in this kind of consolidation here and it works its way through the plura and it gets its way into the plural space. And now because of this I have a fluid that's forming because of all this capillary leakage and inflammation because of the tissue destruction and I got some mcoacterium tuberculosis in there. What's this called? This is called a TB plural eusion. That's really what it is. So that's one thing that can happen is that the TB can spread through the plura and they can get into the plural space. You can also get inflammation. It's kind of like a paranotonic eusion and then that kind of bacteria jumps right into it. So this is called a TB plural eusion. So this is extremely common I'd say with TB. A lot of the times patients who have TB pretty because it's because that kind of consolidation is subpl it's easy for you to get plural eusions. And so it's pretty common especially in TB. So that's one thing. So watch out for a TB plural eusion. The second thing I want you to remember is if these pathogens are eroding their way into the lung tissue and then they get they kind of hop in to your lymphatic circulation or they hop into the um bloodstream. They can kind of spread, right? And this is kind of a really dangerous process. When they spread, they can spread to other different areas of the lungs. And when they spread, they cause like these like little inflammatory lesions that look like kind of like little seeds and they can go everywhere. I'm talking like everywhere throughout the lungs. And that's one thing that we get kind of worried about is when we see like these like small little like looks like millet seeds all over the lungs. This is called milliary TB. So whenever you see like tons and tons of these like little millet seeds or nodules all over the lungs, you can assume that the pathogen has got into the bloodstream or into the lymphatic system or both and it's spread throughout all of the lungs and it's probably also gone into the bloodstream to other areas of the body. Well, what are some of those other areas? Well, one that I get worried about is if it gets into the bloodstream and meninges of the brain, right? That's a pretty terrifying one and we can get something called TB menitis. Now, one thing about TB menitis is that it loves to affect the base of the brain. And so, where you'll probably start to see some problems is right here at the base of the brain. They get a basically kind of a thick exudate that forms around the base of the brain. They get a lot of cranial nerve pausy like cranial nerve six pausy. They get hydrophilis and they'll get menitis signs. And so, that's really important to remember. The other thing is that these pathogens can also get into the bone, the vertebrae. And when they get into the vertebrae, they cause an inflammatory reaction there. And when they cause inflammatory reactions there, it causes basically kind of destruction of the bone. And they get all these kinds of like bone destruction, osteomiitis kind of effect. Sometimes it can cause the bones to fracture. And if they do kind of fracture, it can cause them to displace into the spinal cord. And so this is actually called POTS disease. When it's involving the thoracic vertebrae, we get something called in general the overall POTS disease. All right, it's essentially kind of like osteomi TB osteomiitis. The next thing is it also can again we told you that if you have these mcoacterium and it's in this kind of area of the lung it can spread via lymphatic channels to get into your lymph nodes and then from here it can travel up to your cervical lymph nodes and really cause a lot of inflammation of the cervical lymph nodes and sometimes they can get really enlarged and inflamed and we call that TB lymph adenitis and it's pretty common to affect the cervical lymph nodes. So TB lymph adenitis we actually give this a very special name and we call this a scrula. It's called a scrofula. So it's essentially more likely that the involvement of the cervical lymph node that we're seeing some kind of inflammation involving. All right. So we got the meninges at the base of the brain. We got the actual vertebrae which can cause these kinds of lesions to occur within the bone inflammation. So you get basically an osteomiitis. It can cause fractures. They can displace. They can cause compression of the spinal cord. Here you get enlargement of the cervical lymph nodes. And then another thing is it can actually involve the paricardium. And when it involves the paricardium it's going to cause inflammation of the paricardium at first. So it can kind of cause like an acute paricarditis and so they usually get kind of an eusion that can occur here. So pericarditis is almost always to a degree associated with like a degree of a eusion. All right. The problem with this is that TB continues to cause destruction and eventually repeated bouts of paricarditis can lead to something called constrictive pericarditis. So when I say that a patient can get pericarditis, I what I really get worried about oops is I get really worried about constrictive pericarditis. So let's actually write this down. call it TB per paricarditis and one of the biggest concerns with this is that yes it may cause paricardial inflammation so they get puritic chest pain they also can have that radiate to the trapezius on top of that they could have EKG changes they could have a paricardial eusion they could have kind of a scratchy type of um heart sounds which potentially could be present or decreased heart sounds either way they're going to have that but one of the biggest risks is that if it keeps occurring it under goes fibrosis of the paricardium and then eventually that can cause constrictive paricarditis which can cause right heart failure. So that's one thing to remember. The next thing is the TB can also spread and get into the paritonyium. It can get into the paritinal fluid and you can get a lot of inflammation of the paritinium and you can get some ascites that forms. So that's another thing is not only are you getting um ascites but you're also getting potentially some thickening of the paritinium. And what is this here called? This is called TB peritonitis. Again, it's called TB peritonitis. And one of the key things here is this may cause things like abdominal pain, but you're probably going to see a patient who presents with underlying ascites. So here they'll present with maybe some dullness to percussion, decreased breath sounds in the affected side, puritic chest pain. Here they may have headache, they may have fever, they may have some cranial nerve six pausy, meningial signs. Here they're going to have potentially pain of the vertebrae. So they're going to have pain over maybe the thoracic spine. It'll be tender to palpation. They may even have some neurological deficits. Here they're going to have some really significantly enlarged cervical lymph nodes. Here they can have chest pain. They can have potentially some abnormal heart sounds where it's either diminished or it sounds kind of like a it's like kind of scratching. So like a friction rub essentially. And if it doesn't get better, it can cause constrictive paricarditis which can cause heart failure particularly of the right side. It could spread to the paritinium and cause acidic fluid accumulation and thickening of the paritinium. This can cause abdominal pain and overall sites. On top of that, it can also spread to the adrenal glands, especially the adrenal cortex. And it's usually both the adrenal cortexes, and it causes destruction of the adrenal cortex. When you get destruction of that adrenal cortex, you lose the ability to produce things like cortisol and eldoststerone. And essentially this puts a patient into adrenal failure which we call Addison's disease. So this is technically adrenal TB and adrenal TB is basically a reduction in things like cortisol and eldoststerone which is called Addison's disease. And then lastly it could also go into the kidneys. You could form these different granulomaas within the kidneys, within the urittors, and essentially it causes an inflammatory process that occurs. And inflammation often times causes white blood cells to come to the area. But the problem is that there's not going to be any kind of culture that grows the typical bacteria that we send off for urine cultures. And so it'll grow no bacteria, but they'll have white cells. They may even have some blood in the urine. They may even have some symptoms of dysura. So you'll test them for urinary tract infection and it won't come with a particular bacteria but they'll have pyura. They'll have some signs of some inflammation. They may have some blood in the urine but you would actually have to have a high degree of suspicion to suspect something like genital urinary TB. So these are all the different ways that TB can plague our body. What I want us to do now is take the time to understand when a person gets exposed to TB, when they have scenarios that put them at high risk of progression of the TB, how do I identify what's the best test to give or to do? How do I know when I do a purified protein derivative? How do I know when to do an interferon gamma release assay? When do I get a chest X-ray? What do I look for in the chest X-ray? If I see the chest X-ray, when what kind of tests do I send off for mcoacterium tuberculosis? And then what if they present in other areas of the body? How do I know when I'm going ### [1:32:20](https://www.youtube.com/watch?v=Qjo9F6Uuca8&t=5540s) Diagnostic Approach to TB to have those being involved and how do I test for them? Let's talk about that now. All right, my friends, let's talk about the diagnostic approach. So, when we talk about this, you have to think about the patient who has risk factors for TB. Again, what were they? Do you guys remember? Well, again, the big things for the exposure, the active infection is going to be travel to or born into an area that has a high prevalence kind of presence of tuberculosis. Asia, Africa, Latin America, right? That's one big one. Another one is crowded settings where it can be spread via those respiratory droplets. Prisons, homeless shelters, those are high revolence region or high-risisk regions. Healthcare workplaces. Another one is going to be close contact within again a family, friend, anybody who has active TB. This is probably one of the highest risk components. Okay? So, close contact with somebody who has active TB is probably one of the highest risk components for TB exposure because you may get a high inoculum of that microbacterium. Now, the other thing that not only controls the infection by TB, which is the exposure component, but the other one is the risk for developing active TV for it actually progressing becoming primary progressive or going out of a latent state into reactivation. What were those? HIV AIDS is going to be a really important one. I am immunosuppressive medications. One of the common ones that we really get concerned about is TNF alpha inhibitors. The other ones are transplant recipients. Why? Because they're on usually some type of immunosuppressive therapy for kind of like the transplant like rejection meds. The other things could be diabetes, chronic kidney disease, and even silicosis. So these are some potential risk factors for where the patient could progress to an active disease, primary progressive or come out of the latency and go into reactivation TB. The concept behind this is that again it's probably some degree of an impaired immune response. So your tea cells are super critical because they're releasing things like interferon gamma. They're also releasing things like tumor necrotic factor alpha. The macrofasages are also releasing All of these things are helping to control your immune response to generate granulomaas to maintain granulomaas. Right? So in patients who have HIV AIDS, they have about a 50 timefold increased risk of developing active TB. Those is because they have reduction in their overall T- cell population. So they have reduced CD4 counts. That reduced CD4 count leads to reduction in interferon gamma, reduction in tumoric factor alpha. The inability to either maintain or form granulomaas may occur. The other component here is the TNF alpha inhibitors. TNF alpha inhibitors, you're going to suppress TNF alpha. If you suppress TNF alpha, you reduce that overall immune response. And so again, you reduce the ability to maintain and form gran form granulomaas. So that's the concept that I want you guys to think about for that individual who is high risk for exposure. Close contact is a really big one. Born into or travel to an area with the high prevalence regions are going to be the biggest risk factors for exposure. And then HIV, AIDS and imunosuppressants is going to be your highest risk factors for that possible infection becoming progre primary progressive or coming out of latency and going into reactivation. So that's the particular things for risk factors for exposure and active infection. What would be the potential signs and symptoms of tuberculosis and do they have any? The big things is pulmonary TB. So pulmonary TB is likely going to be the most common presentation that you would worry about. This is going to be fever, night sweats and you know probably more of a prolonged course of these fever and night sweats. The other one is they can have cough. It could be perent especially in the individual with reactivation TV or hemopysis and this could be due to reactivation TV creates this kind of liquefosis of the caseia center and then that kind of erodess through the actual bronchi and it can cause little aneurysms of the pulmonary artery branches. it can erode into the bronchial artery and lead to hemopasis. The other one is weight loss. Usually this is an unintentional weight loss usually greater than 10 pounds or so within a very short time frame. And again this is probably because of the cytoine storm. So cytoine storm and this is probably due to the destruction of the miccoacterm tuberculosis especially in the reactivation stages because of the destruction of the actual bronchial tissue the alvolar tissue. All right. So do they have signs and symptoms? No. All right, the next question that you ask is because this is could be a latent TB. And one of the best things about determining latent TB versus no TB is do they have a memory of the actual antigen. All right, so you need to know do they have memory tea cells that if they were exposed to this, they would remember and they would generate a reaction. The way that we determine that is via what's called interferon gamma release assay and tuberculin skin tests. One of the first questions to know which one of those tests you do is did they have the BCG vaccine or not? If they did have the BCG vaccine, that changes things. If they don't, that changes things. So, for example, if they did have the BCG vaccine, we should probably go and do what's called an interferon gamma release assay because if we did the tuberculin skin test, they may have a false response. And that's not what we want. We want to know, do they have an exposure component? If they do have an exposure component, they could have latent TB. If they don't have it, then this could be just completely normal patient. The interferon gamma release assay is very good test. What we do with this is we're trying to see their response. All right? So you collect blood from the patient. When you collect this blood, let's say that this patient is infected with the mcoacterium tuberculosis. You're going to collect the blood. What's going to happen is you're going to take from that blood, you're going to basically expose the patient to like very specific types of antigens. All right? Usually this is like two different types of mcoacterial tuberculosis antigens. What's going to happen is when they get exposed to it, the macroofage if they've, you know, they'll take it, express it on its MHC2 complex and take it to a T-helper cell. That T- helpper cell if it's recognized it with its T- cell receptor it'll generate an immune response. What kind of immune response? It'll pump out what? Interferon gamma. If it pumps out interferon gamma at really high levels above that threshold value that is what makes us concerned that they have a prior exposure in a T-C cell memory. And then we can measure that interferon gamma via process called ELISA. Essentially we use antibodies to tag it. wei attach a fluorophor on it and see if it comes up. If it's no, you can get your tubercul skin test or your purified protein derivative. This is essentially what you're doing is you're taking and injecting intramally like 200 like microbacterial antigens into the actual dermis tissue. What that's going to do is you're going to kind of expose them to potentially antigens that they've either recognized or they haven't recognized. If they have recognized and they have memory of it, your macrofasages, your dendritic cells, they're going to come in, they're going to process them, present them on their MHC2 complexes, take to your T- cells. Your T- cells are going to pump out what they're the interferent gamma. That's going to cause more of a granuloma. You're going to get a big induration on the skin. And so you should get like a little bump. That bump size is really contingent. In other words, we can set thresholds. And so the smaller it is, we would consider it to be positive in those individuals who are extremely high risk. Do you guys remember the high-risisk patients? HIV, AIDS, any of your immuno compromised states and the close contact exposure. That's going to be the ones that if they had any of those potential risk factors and it was greater than or equal to 5 millimeters, I would consider it to be abnormal. And that would be a positive test. Now, I could say, all right, cool. What about 10 millime or greater? If it's greater than or equal to 10 millimeters, again I have to set the threshold because generally anything greater than or equal to 15 is positive for anyone. It doesn't really matter. All right? Generally use this as part of your pre-employment screening. If it's positive, it's anyone. All right? But we may have to lower the size of it to based upon a particular risk factor. Now it's not the immunosuppressed patient. close contact exposure with the person with active TB. Now it's those individuals who probably work in the healthcare. They work in prison. Uh can't they're in prison homeless shelters. They traveled to an area that was you know high prevalence of TB. Those are the particular patients I would actually kind of lower that number for. All right. So greater than equal to five that's for the patients who are extremely high risk. We're lowering the threshold significantly of that size to consider to be positive. 10 or greater. All right. That's for again higher risk, but it's going to be more healthcare workers, prisons, homeless shelters, travel, things of that nature. The time when it's 15 or greater, that's anybody. It doesn't matter. So, anybody, you don't have to have any risk factors, exposure, risk factors for active disease. It's just generally this is things that people get done for a part of their pre-employment scanning. And if it comes back positive at greater than it comes up greater than or equal to 15 millimeters, that is considered a positive test. And all that means is that you have memory. you've had exposure to the TB antigen. All right, so at this point we have a person come up with a positive interferon gamma release assay that tells me they have memory. They come up with a positive tubercul skin test or purified protein derivative that tells me that they have memory. The next component is determining is it latent or is it active TB? Because active TB can be asymptomatic, right? All that means is they don't have to present with things like fever, night sweats, weight loss, cough that's either rich in sputum or rich in blood. That doesn't have to be the case. Sometimes they can be completely asymptomatic. So the question now is do they have any signs of lung tissue destruction that maybe didn't cause symptoms? That's where a chest X-ray comes into play. If the chest X-ray is normal or they have like some areas of fibrosis and calcifications that could have been a healed up area which we call a ranky complex and all that really is if you look at this you can notice that there's a hiler lymph node that looks a little bit calcified and fibroed and then over here you probably had a gone focus that became calcified as well and fibros that is called a ranky complex. It's a fibrocalification of a gone complex which is a gone focus and hilonopathy. Right? So this would be potentially a sign of healed up area. Um and it's a really common sign for latent TB. So the chest X-ray could be normal or you could see a healed up area of a gone complex. That would be a sign of latent TB. All right. So latent TB is they usually have a normal chest X-ray. They have no signs of active tissue destruction but they have memory of TB exposure. All right. The other scenario is you can get an abnormal chest X-ray. So what this means is it could really look a bunch of different ways, but again it's not going to be normal and you're not going to see a ranky complex. You're couple different things. So for the first one is consolidation. So you're going to see a consolidated area, especially in primary progressive TB. It really loves to hit the middle and lower loes. And so what I'd be looking for is I'd look at this patient. I'd look here and what I see some opacity here in this particular area, especially of that right lower lobe. If I see a right middle lobe, right lower lobe opacity and they have potential again they have memory per se of a T uh TB exposure maybe they have some symptomatology and they have this consolidation I would start to potentially consider something like a primary progressive TB. The other component here is if I saw hileryinopathy. So hiler lymphodenopathy in this scenario here you're going to look at this. You see a pretty significantly enlarged lymph node and you can see some consolidations over here. This is pretty consistent with a person having again TB findings. This would be more of a primary progressive TB. Apical cavitation is that sign that again it was a person who went latent. They had a simon focus. It got reactivated. it caused liquefactive necrosis or liquefied the case necrotic core and you ended up with this cavitary lesion. And so over here you can notice that there's definitely some weird broncogenic spread some opacities. But up here in the top look you notice this cavitation that's pretty consistent with apical fibroacius cavities which is very consistent with tuberculosis especially reactivation TB. If you see this one, you should be very scared because this is a part of where it's probably the worst case scenario that TB has probably gotten into the lymphatic system. It's probably got into the circulation. It's spread all over the body, but it's just spread to multiple areas of the lungs and these are called diffuse nodular lesions. If you see something like this, this is called milliary TB. And the concept behind that is if you look at them, they look like tiny little millet seeds. All right? So, this is a very, very concerning sign. And this would be indicative of pretty significant dissemination or lymphohhematogynous spread to all different areas of the lungs. And it's probably in extra pulmonary organs. Meaning it could be in the heart, brain, it could be all over the place. All right. So if you see these potential signs, this would make you think about active tuberculosis. All right. Now, we got to active TB in what way? They have the risk factors. They didn't have any signs and symptoms. We test to see if they have memory. They do. They don't have an abnormal chest X-ray, latent TB. They do active TB. What if the patient did have signs and symptoms, and you got the chest X-ray, and it showed one of these potential findings. Is that active TV? Yes. Here's the thing. You can have a patient who has active TB get the tuberculin skin test, get the interfering gamma release assay, and it can give you a false negative. Especially if the patient's extremely immunosuppressed, we call this energy. they may not have the actual appropriate response to trigger an interferon gamma levels that are really high or cause a granuloma that's going to form underneath the skin in a tuberculin skin test/purified protein derivative test. All right, so if they have this and they have an abnormal chest X-ray, great. But if they have symptoms and you get the chest X-ray and you find one of these things, that could also lead you to suspect active TB. Now, at this point, this doesn't mean that we have TB. It just means that we have a high suspicion and then we need to confirm it. But what if you had a patient who you got the chest X-ray, they have signs and symptoms. They have all the risk factors. Maybe they had memory. Maybe they didn't of the actual TB exposure, but you didn't see anything on the chest X-ray, but they are immuno compromised. They have HIV. They're on TNF inhibitors. You have all of the things that make you can still have a high degree of suspicion and concern that they may have active TB and you're just not seeing it on the chest X-ray. Those are the times you can get a chest CT. Chest CTs are very sensitive and it can show you a lot of things that you miss on a chest X-ray like what all the same findings. It's just it's going to be way easier to see. You can see consolidation and again you would notice here's a pretty obvious consolidation. You can say notice hiler lympadenopathy. So if you notice middle lower lobe uh consolidation with hympidenopathy it screams more of a primary progressive TB. And here you can notice that there's a lot of lympadinopathy here present. If I notice apical cavitation, those fibroacius cavities in the upper lobe, this is extremely consistent with reactivation TV. Here's the cavity and you notice a lot of this inflammation around it, that thick walled area. All right. Another one is called diffused nodular lesions. Again, if you saw this on the chest X-ray, it's you'll be able to see this on the CT scan, but you can notice, look at all of that millet seeds, diffused nodular lesions all over the lung. This is very concerning for dissemination. So it's lymphohematogenous spread of the TB throughout the body. In this case, it went to all over the lungs and it's probably in other areas, extra pulmonary organs, if you will. The other way that you can find this is called a tree and bud pattern. So this one's also pretty consistent with reactivation TB. So reactivation TB, look for apical cavitation. Look for the tree and bud pattern. Sometimes the milliary presentation as well. The primary progressive, you're looking for the consolidation and the hiler lymphodenopathy. But tree and bud apical cavitation definitely think about the reactivation TB. So what you would see here is you'll notice something. You'll notice that there's what's like called bronchiacttoysis. So you'll get some kind of enlarged bronchioles and you'll notice some exudates or kind of like little inflammatory areas that are outside of it. We call this a tree and bud pattern. So here you're going to have the tree trunk and then all of these like little bud pieces. That's going to be pretty consistent. And so this is kind of a sign of endob bronchial spread. Um because what happens is again we talked about this on the whiteboard is when a patient gets TB especially reactivation TB they have that liquefied case necrosis that kind of erodess its way into the bronchial into the bronchios and when you cough it can then spread or it can move all over the place. So this is an example of that endo bronchial spread if you will which comes from reactivation TB. So if you see any of these types of imaging whether it's chest X-ray or chest CT and again they have signs and symptoms and they may or may not have positive testing I mean interferon gamma release assay tuberculent skin test purifying protein derivative because if they're severely immunosuppressed they may have energy either way symptoms and memory and they don't have energy and they have imaging whether it's chest X-ray chest CT that would tell you if it's active TB these two primary progressive. This one here and this one here tells you that it's more likely a reactivation TB. Diffuse nodular lesions is extremely concerning because at this point we're worried about milliary TB that this is spread into the blood into the lymph node lymphatic tissue and it could be all over the place and that's a really concerning feature. So with that being said, if I did see a milliliary pattern on chest X-ray or CT or they presented with extra pulmonary symptoms, meaning that maybe the TB went to another tissue, created a caseing granuloma and led to symptoms due to that in the actual inflammatory reactions and damage that kind of granuloma caused in that suspected tissue. What would that look like? Well, again, if I see this milliary pattern, I'm already concerned that this is in other areas of the body besides the lungs. So, I'm starting to think, could they have extra pulmonary TB? If they present with symptoms, I start to be concerned about extra pulmonary TB. So, the question is what are some of these symptoms, right? So, for example, if they had headache, if they had menismas, which is kind of like a they have a hard time being able to kind of flex their neck, right? or they have a lot of stiffness, rigidity, maybe they have the Brazinski sign, Kernig's test, they're confused, they have cranial nerve pauses, especially cranial nerve six where they have difficulty being able to abduct the eye. Then you might start to think about potentially TB menitis. The concept behind why six nerve pausy is super common here is because it loves the base of the brain. So it likes to get towards like the actual brain stem area. That's where it likes to cause a thick exodate. puritic chest pain, dullness to percussion, decreased breast sounds on the affected side. This is probably a plural eusion and TB spread through the lung tissue, especially in scenarios like if they had primary progressive TB, they're usually subpl where they first start off and then they kind of spread. In this case, they could spread through the plura into the plural cavity and they can get TB uh what's called TB plural eusions, right? And so this would be concerning. Another one is if they have chest pain, muffled heart sounds, maybe they have peripheral edema, acites, hpatomegaly, JVD. This could be signs of pericarditis. And one of the concerning features is it acute pericarditis or is it potentially constrictive pericarditis. Usually acute pericarditis will cause kind of a chest pain that changes with position radiates to the trapezius. They may have kind of a decreased heart sound if they have an eusion. They may have also a paricardial friction rub. And then again peripheral edema ascites hpatomegaly JVD. This is a patient who probably has had repeated injury and repeated inflammation of the paricardium that it became fibrous and they have constrictive paricarditis. But either way I'd be concerned about TB paricarditis. Another one is abdominal pain ascites. This could be a concern of TB peritonitis. If they have urinary frequency changes, hematia, you test their urine, it ends up with a lot of white blood cells, but you get a culture and it shows no types of typical bacteria. It may not be a UTI. This may be genital urinary TB. If you have back pain, tenderness over the vertebrae, maybe neurological deficits, potentially some weakness, maybe some numbness, some tingling, some paristhesas of the extremities. This could be signs of a potentially osteomiitis of the bone which we call POTS disease. All right. The other thing here is it can cause uh it can spread to the lymph nodes. So it actually starts off in that hiler lymph node and it can spread to the cervical lymph nodes. And when it gets nodes, it can cause a pretty significant case and granulomaas and inflammation there and cause lymphatinitis. And cervical lympadinitis is pretty common with this one and it can be called a scrollula. And so that's something that you may also see. Hypotension, hyponetriia, hyperalemia, hypoglycemia and a TB concern is almost always concerning for adrenal insufficiency or T adrenal TB. The concept behind this is that if you damage the adrenal cortex, you lose the ability to release cortisol. So that can cause hypotension and it also can cause hypoglycemia and you also lose the ability to release aldoststerone. So that can contribute to hypotension, hyponetriia and hyperc calmia. So that would be concerning for adrenal TB. All right. So if they have none of these then what are we thinking? All right. Well then I'm not really worried about this being extra pulmonary TB. And what I can do is I can say I have a really high degree of suspicion that they have pulmonary TB. So I have a suspicion because either a couple things. One is they had symptoms or they had a positive test and an abnormal chest X-ray. So they either had symptoms, they had memory, but they had a positive chest X-ray. All right. From there, I need to say, do they have sputum? That tells me that TB is the cause for these symptoms. Abnormal chest X-ray and weird memory of TB exposure. So what you do is you get three sputum samples 8 to 24 hours apart. You have to at least get them kind of preferably in the early morning. When you do that, you're going to obtain all of the sputum and you're going to send it off to a lab and you're going to run a couple different tests on it. The first one that you're going to run is an acid fast basillus smear. This one is good because it tells you if you exposed if you're exposed to a mcoacterium species. Doesn't tell you if it's mcoacterium tuberculosis, mcoacterium aven. All right. Nucleic acid amplification test is another one that you would do. And this one's pretty great as well because what it's going to do is tell me if they have specific DNA sequences that we have already pre-identified in the past that tells me it's exactly mcoacterium tuberculosis. Right? And the last way is we can get what's called a mcoacterial culture. And so we're basically going to collect this, grow this on a specific medium, and it's going to take some time, probably two to eight weeks, but it'll grow out the actual miccoacterium tuberculosis. This would be your gold standard. It just takes a while. So, if you had to pick a test, which one would you pick? Well, this one tells me I have mcoacterium, but it doesn't say if it's TB. This one would tell me if I have microbacterium tuberculosis, but this would be the gold standard. So, I'd start off with this as the rapid test, and this would be your gold standard test. So, if you have any of those, again, preferably you have to have at least like one of these two. And then I'd prefer this one overall to determine if the patient has active TB, especially pulmonary if you're checking it from a sputum sample. Again, what am I trying to get across with this? The point of this is confirming that they have mcoacterium tuberculosis. So, if you do the acid fastillos smear, what are you doing? You're looking to see if you try to decolorize, do they decolorize? All right? And all that tells me is if they have lots of micolic acid which is common in mcoacterial species and so they would stay red. They wouldn't take on that bluish color whenever you give them the counter stain of the methylene blue. But it doesn't tell me if it's mcoacterium tuberculosis. It just tells me it's mcoacterium. The nucleic acid amplification test is we're literally taking the bacteria. We're extracting out the DNA. We're then going to amplify it and then we're going to see if we test it and we actually know the specific DNA sequences that are present in microbacterium tuberculosis is it present and if it is and we have this proper connection boom we'll confirm that this is mcoacterium tuberculosis based upon the DNA sequences and the other benefit of this is because you can test those DNA sequences you can determine if the patient is susceptible to the common antibiotics that we give them or antimicrobacterial if they're not and we have to give like more of the multi-drugresistant type of like antibiotics. All right, so that's the other benefit of that. The culture is the gold standard though. It's just the downside is it takes a long time for this thing to grow and so you'll have to wait a while. But if you get this coming back, it is going to be the most definitive that the patient has mcoacterium tuberculosis. All right, so that's the beauty of this is that it gives you two things. One is it diagnoses it and the second thing is between these two is it actually helps you to determine do they have a resistant strain or not will they respond to rafampid to isoniz or will I have to use different types of drugs all right if they did have that millary pattern the diffused nodular lesions I'm concerned it's all over the place if they have any extra pulmonary symptoms or if they have both of those I'm concerned that this is all over the place so then I got to start thinking a little bit more and then I may have to do an organ specific workup and test those areas. Test the fluid, test the tissue in those areas and do all these same tests. It's just not going to be from a sputum sample. It may be from a fluid a tissue biopsy. But I got to go through the same steps. find the extra pulmonary TB first. So let's say that I have a concern that they have TB menitis. What would I do? I get a CT head. What I told you is it loves the base of the brain and you're going to get menitis and it loves to attack this area right here. So it chalks up all the arachnoid villi. It causes a communicating hydrophilis. So you would notice the thick exidate here and you notice some enlargement of the ventricles. Here we have enlargement of the third. lateral and we have enlargement of the fourth ventricle. So this is pretty consistent to see hydrophilis and kind of a basil meningial enhancement because it causes a thick exudate there in that base of the brain. All right. If that's the case, I'm going to get an LP, send it off and see if it comes up again with what? Well, the preliminary test is I check glucose, right? I'll check also my um types of cells. So I'll see if they have any white blood cells or lymphocytes. I'll check um the glucose. I'll check the ADA and I'll check the proteins. And ADA is a really good marker because it helps to identify the possibility of tuberculosis. Right? So again from here I'm going to tap in, collect some samples, send it off to the lab, and when I do that my goal is to see if it comes up with some characteristic signs. So what are those signs? Again the big thing is high protein. They're going to have low uh high lymphocytes, low glucose, and they're going to have a high ADA, right? Adenosine diaminase. And this is kind of one of those like little tests that I'd say is the most important out of this fluid sample. From here, out of all these things, what I then need to do is I need to confirm the pathogen. This doesn't tell me if I have TB. So, what do I do? I get all those microacterial tests, right? And I do all of those things like the nucleic acid amplification test. I do the microacterial culture, maybe the acid fastillos smear, right? TB plural eusion. Based upon that, what am I going to do? Well, if I haven't already, I'll get a repeat image and I'll take a look and see if I can find if there's any plural eusion. And if I see a plural eusion like this, look, I mean, come on. That's a plural fusion if I've ever seen one, right? There's a good crosstophrenic angle here. Ain't none there. That's pretty consistent with the plural eusion in that scenario, especially in this one. I got to tap it. I got to test the fluid. If I test the fluid, you're probably going to see a lot of the same things. You may see, you know, high amounts of protein. You may see potentially um high amounts of LDH. high amounts of lymphocytes and maybe even a low glucose. But what's the big thing that I'm looking for? If I tap into this, I collect the fluid. I say, "Let me send this off to the lab. " I may see lots of proteins, I may see lymphocytes, I may see ADA. And again, you may even see low glucose, too. But the ADA is the precursor that says, "Oo, my pre-EST probability of TB is a little bit higher. Let me send this off to test him for again nucleic acid amplification test the acid fast basicillos smear the mcoacterial culture all right TB paric you're gonna get the point here TB paricarditis what am I going to do well in these scenarios probably an echo is going to be the best thing because it's going to give me an idea if they have a paricardial eusion that's probably the first thing I'd be looking for especially an acute paricarditis if I see that eusion that's concerning but guess what gives me an opportunity to stick a needle in there and test it and say oh there's some fluid I get that fluid I send it off to the lab and what am I looking for? Probably you're going to have lots of proteins. lymphosytes. You may have low glucose. But what are you looking for? It's the ADA. That's the precursor. That pre-est probability is up. I'm going to send it to get the testing. I hope you're getting the point. If you didn't, guess what? We're going to do it again. TB parittonitis. They have a sites. What's probably the best test here? Well, I could do a CT scan. I could do an ultrasound of the abdomen. But again, I need imaging to see if I have any evidence of ascites. And so if I see the ascites, I see the paritinal thickening here. All this dark material is going to be the ascites. And then that thick layer around this is the thickened paritinium. That's pretty consistent with a paritonitis. What do I got to do? Tap into the ascites. When I do the parasentesis, what am I going to do? Send off the fluid. If I get all that fluid tested, what am I looking for? Well, dude, yeah, if I tap in and I go ahead and collect this and send it off, I'm probably going to see lots of lymphosytes. proteins. I'm probably going to see maybe a lower glucose. the sag ratio which look at your um your ascites albumin gradient anything less than 1. 1 pretty much always concerns you for an exodative process rather than a portal hypertension related process right and so ex exodative is almost always a concern for things like malignancy so at that point malignancy or in this case TB is another big one but sag less than 1. 1 means it's not portal hypertension related plus I'm going to have probably lots of lymphosytes protein low glucose but again what's the key thing the ADA Okay, that's the litmus test to say, oop, let me send this off for microbacterial TB workup. All right, that's the that's that part. General urinary TB is a really weird one. This is a person who came in for that hematia. Maybe they have some frequency in their urination. Maybe they have some disura. You get a urine sample, you get a culture, it all comes back relatively like, you know, non-specific. So they have some pyura, right? So white cells in the urine. They have some hematia. Maybe their luccoite eststerase and nitrites are maybe elevated, maybe they're kind of fine, but the key thing is you get the culture and it's not positive for any typical bacteria because microbacterium has to grow in a specific medium. So you would have concerns of what seems like a UTI, but they don't have any bacteria to prove it. You might start them on antibiotics, etc., but it may not get any better. You do the CTU, which is a CT uroggram, and what you're looking for is any evidence of granulomaas. And so in this patient, if we look here on their right kind of kidney, we notice that they have this hypodense collection and they have some calcifications here. That's kind of consistent with potentially a granuloma there. All right, same thing. That would make me think that there's a possibility they have a granuloma due to TB in the kidney. So what do I need to do? Well, I'm going to probably collect a sample probably from their urine. Sometimes if I need to, I can do a biopsy, but what I'm going to do is I'm going to send that off for the microacterial TB workup. All right, I hope that you guys get the point. This is what you're going to do with all the fluids. All right, but what if I don't take it from a fluid, I tissue. I got to confirm it. So, I'm going to do the acid fast basic smear. I'm going to go ahead and do the nucleic acid amplification test. I'm going to do the microacterial culture. And if they all come up positive, it's going to confirm my presence of extra pulmonary TB. All right. Now again, the benefit of doing all of these cultures, as I already told you, it's determining if they have it, but it also gives you guidance on to is the actual microacterium TB resistant to your classic drugs that we're going to give them like rafampen and is it? If it is, we have to change up the type of antibiotic. And we'll get into that later. All right. What if this isn't a fluid? Instead, it's more of a solid tissue. Well, then we may need to biopsy, right? So, and spinal TB is something of POTS disease. You get an MRI. If anybody has back pain, neurological deficits, vertebral tenderness, and they have a suspicion of TB, I'd probably get an MRI. When you do that, you're going to look for vertebral body destruction, and maybe even spinal cord compression. So, you look at the I don't want to go too crazy in the radiology aspect here, but this is a T1 image. And with this T1 image, you're looking for areas of anatomy, but darker areas, so hypoensities. And so, I can kind of appreciate this. There's some hypoensity here, here, here. There's even some over here. There's some here there things all over the place, right? And then I'm going to look at the T2. When I look at the T2, you're looking for hyper intensity. And this is again areas of edema, inflammation that you're looking for. And so, a little bit of white here. Um, some white down here, white here. A lot of white in that disc space. There's some white outside here, white outside here. All right. So, that's some areas of again edema, inflammation, possible disease processes on the T2. The best thing is looking at the T1 postcontrast and that's going to show a lot of enhancement. Um, and so here I can notice a significant amount of white here, here in the vertebral bodies going into the disc going outside of the spinal cord. Um, over here, this is probably a cold abscess potentially. But this is all signs of again inflammation um, and that rim enhancement. So this is pretty concerning and consistent with someone who probably has potentially some disease process their inflammation destruction of the vertebrae the parispinal areas. Um, and then on top of that, guess what else I notice because of all of this? It's squeezing on the spinal cord in every single one of these, right? So, I have the cold abscesses right there. But then I also notice all of this spinal cord compression. So, this is pretty consistent with like some spinal TB or POTS disease. And this would again in this scenario, what would I may need to do? I probably have to go in and biopsy this. And so, you may need to do some type of CT guided or f ultrasound guided a bone biopsy. Take a tissue. Once you take that tissue, you're going to have to send it off and actually be tested. Do the acidifas aspicillus smeare do the nucleic acid amplification test do the microbacterial culture and you may even do hisystologology on it to see if you find case and granulomaas. If you have the patient with a scrofula, right, something like this, then what you may have to do here for that is again a lymph node biopsy. You can do excisional, you can do FNAS. Again, I kind of think it depends on these potential scenarios by excisional is always going to be best. But if you did one of these, you're going to take that tissue sample and what are you going to do? You're going to send it off to the lab because once you send it off, you're going to test it for acid fastillos, nucleic acid amplification test, macterial culture, and hytologology. All right, adrenal TB. and this potential patient, you're going to be having the signs. What would you do? I'd probably get imaging. I'd look to make sure I don't have like a tumor. I don't have something going on where they're kind of like hemorrhaging or they have waterhouse Frederickson syndrome. I'm going to get some imaging. So, I'll get some type of like adrenal insufficiency work up with imaging. I'll check their cortisol. I'll check their eldoststerone. I'll even probably check their sodium, their potassium, all those things. And again, we talked about it. Low cortisol, high ACT tells me that this is a primary adrenaline sufficiency because low cortisol is coming from what? It's coming from the adrenal gland. Low cortisol should tell the pituitary to do what? Make more ACT. That's the reflexive response. And that tells me that this is coming from the adrenal gland, right? They're going to have low sodium, high potassium because of low eldoststerone. All right? And the glucose is going to be low because of the low cortisol. You get the adrenal CT, MRI, and you'd see some bilateral adrenal enlargement and probably some calcificating lesions. And so the adrenal glands are normally difficult to find, but here you can actually see this one on the left side a little bit more so than on the right side. But you see some calcifications and a little bit more enlargement I'd say on the left than so than the right but that's some bilateral adrenal enlargement with definitely some heavy calcifications that would make me concerned and TB loves both if it causes adrenal insufficiency usually you get bilateral adrenal destruction all right so then I would have to biopsy and guess what I'm going to do with that biopsy I'm going to send it for an acidifasillos smear I'm going to send it off for uh a nucleic acid amplification test mcoacterial culture and estologology to see if there's case any granulomaas So you guys get the point. I'm doing all of these things to prove that TB is somewhere else and that's where those tests come into play. Again, that's still the same process. The only thing that's different is I take some actual tissue and I look at it under the microscope and I want to find case granulomaas. And so this is a little bit excessive. This is probably more for your step one, your basic MCQs. But here you can notice that there's a lot of this case necrotic center. And then outside of it, you're noticing some of these Lang Hans giant cells. And that's kind of just telling me that I have again signs of Caseiating granulomaas. All right. So that is a way that I would prove that the patient has extra pulmonary TB. Man, that was a lot ### [2:09:24](https://www.youtube.com/watch?v=Qjo9F6Uuca8&t=7764s) Treatment of TB right? But again, I hope you guys get the point out of all of this that this is really trying to kind of teach your mind to think about TB in a couple different ways, which is latent is they have the memory, but they don't have the imaging that supports active disease. active, it could be pulmonary, it could be extra pulmonary. Active TB, if it's pulmonary, again, you're looking for either memory or symptoms plus imaging that suggests it. If they have extra pulmonary, if they have milliary TB, it probably is somewhere else. If they have extra pulmonary symptoms, you got to find where it is and then test it to see if it's in those places. If it's not in other places and you're concerned that it's in the lungs, you got to take sputum and collect that and see if it comes up positive for the miccoacterium tuberculosis species. All right. Now, when we confirm that a patient has TB, it's important to determine if it's latent or active. Latent tuberculosis is treated with things like rafampen, and you can do that by itself for about four months. That's probably one of the common ones that we utilize a lot of. Another option is all right. And you can give it with rafampen. So then you could drop the time frame down to about 3 months. All right? The only thing that you want to do is anytime you give um isid, it can cause puradoxine or B6 deficiency and that can lead to neuropathy. And so we give pyodoxine with this empirically to reduce that risk of neuropathy. But again, you can drop your time down by three months since you're giving two drugs. Another option is you can actually do is you can do rifentine which is just basically it's like an it's a rifomy. It's an alternative to rafampen. And then on top of that you can again give the pyodoxine because anytime you give is usually give puridoxine to reduce that B6 deficiency related peripheral neuropathy. This one you can also do it for three months but the benefit of this one is that you can do it weekly but usually you need to this is for a person that you're kind of concerned with adherence and usually there needs to be direct observation that they're getting it. Um so this is an alternative as well. Another one that we can do is it by itself. The only downside about that is that again you're going to have to give it with the paradoxine to reduce B6 deficiency related neuropathy. But this one you have to be on a little bit kind of like longer. All right? So you may have to be on this for 6 months sometimes 9 months. And so that's the downside of this one. This one used to be the pretty common one that we would give is isid for six to nine months with paradoxine or rafampen daily for four months. So that used to be the pretty common regimens that we would kind of abide by. So asterisk here tells me the which ones we usually would go off of on the exam. This was just a little bit extra to kind of go into a little bit more detail about other opportunities. This one is going to be pretty good because you can do weekly. So, it's going to be preferred, but you need direct observation therapy to assume that they're doing this one. So, there's a lot that we talked about here, right? If you don't remember any of this, that's okay. Latent rafampen for four months or isid for six to nine months. All right, that's really the big thing to remember. If you wanted to take it to the extra step, you could think about it like this. For those who have contraindications to rifamy, rafampen or rifipentine, what that tells me is I probably can't give them something that has these in it. I probably only give them isid. All right, if that's the case. So, what would that be? It's drug interactions. Usually, people who have HIV medications, um maybe they're on like a blood thinner of some sort like warin or an anti-coagulant of some sort, which is interacting with a cytochrome P450 system. Rifomy alter the cytochrome P450 system. they're inducers and so because of that they could reduce the efficacy of other drugs that are being taken with it and that is concerning and so because of that we may not want to give that drug to this patient and if they do have that that's probably where is going to be your go-to if they don't you could probably just stick with saying we're famping and you're done but if you wanted to take it to the ninja nerdy level that's when we kind of get a little bit more and we say are you worried that they're even going to take their medication All right. If you are, go with this option because you need direct observation and plus they're not going to have to take it daily. They can come in weekly. You give them a pill. You watch them. All right. Go. I'll see you next week. That's a good option. All right. The other one is, do they have things like HIV? Are they really young? If that's the case, then we prefer to go with the rafampen and again isid with the B6. All right. If it's not, you can probably just go with rafampen for four months. Again, if you don't want to remember all of this, you could just say, do they have a contra indication to riffins? Yes, go with the isizid. It'll just be prolonged. If they don't, you can probably just go with rafampen for four months. All right. If you wanted to remember this extra stuff, cool. But that's what I want you to remember for latent TB. The reason why you're treating latent TB is not because they're contagious, not because they have active like disease going on. You're trying to knock this bacteria out and eradicate it completely. And that's the goal here. It may be dormant, but there's always a possibility in the future that it could reactivate. And so, we're trying to reduce that reactivation risk and eradicate the pathogen in general. Now, active TBS, they either have already reactivated or they progressed from their primary infection. All right? And they have consolidation hympidinopathy or they have reactivation with the apical cavitations. All right? They're causing active disease or it's other areas of the body. It's already in the brain. It's in the plura. It's in the paricardium. It's in the paritinium. It's in the kidneys. It's in the urer. It's all over the place. Now, we have to change up our regimen. Rafampen by itself, is by itself ain't gonna cut it. We have to be more aggressive. And we're going to combine a bunch of different drugs up front. And so, we give rafampen. We can also give isid, we give pyenomide, and we give ethmutl. All right. So, this is called the ripe regimen. You're going to do all four of these drugs for at least two months. Then after that you're going to go to just two of the drugs which is just the R and the I. So then you'll go to rafampen and isid for another four months. This is the standard. All right. So in most case scenarios it's ripe regimen all four of them for two months and then rafampen and isid for the remaining four months. All right. So two four that's a total of six months that you're going to be on TB medications. Right now, the things that you need to tell the patient of is when you start these medications, there is possible side effects that you need to watch out for. If they come back saying, "I'm dying because I noticed that my tears are red and I'm peeing red orange color. " You need to tell them that's a normal process to have red orange tears. So, rafampen red orange tears. And make sure that you let them know it revs up the liver. All right? So, it's a cytochrome P450 inducer. What that tells you is that you need to let them know, hey, we got to be careful. If you're on warrin, if you're on HIV medications, we may have to check those medications and be very, very careful because this could reduce the efficacy of those drugs. And so, you may need to check their INR more carefully. be able to modify some of their warin, modify their HIV medications, etc. All right. Is it I want you to tell them watch out for isolated nerves to become angry. So, peripheral neuropathy. How do you prevent this? giving them puradoxine. Pyroenomide, watch out for a pyramid of uric acid that can cause things like gout. It can increase the risk of uric acid stones like nephrolithasis. And so pyroenomide, watch out for gout or hyperurasemia. All right. E, watch out for the eyes to be damaged. So optic nuritis, they may have changes in their vision, uh, particularly the color component of their vision. And so this is one that you may need to do annual eye exams keeping an eye very closely on their eyes and making sure that you stop this at any point in time if they have any signs of optic nitis because they could lose their vision. All right, so these are really critical but I'm going to take it to the next level. I want you to remember not just those things but rest in peace liver. So rafampen isid and pyizenomide. Pyenomide is actually the most toxic to the liver but these will put that liver in the ground. they can cause hpat toxicity. All right? And so that's why it's really critical for you to be monitoring these patients LFTs when they're on these drugs. All right? So that's what I want you to take away from that. So latent, if you don't remember all the other stuff, that's okay. If they have a contraindication to being on rafampen, give them for six to nine months. If they don't, give them rafampen for four months. If they have active TB, all right, ripe regimen for two months, refampen isid for four months, a total of a six-month period. Watch out for these side effects that are all present. Keep an eye on them. Monitor the things appropriately. All right. If you want to take it to the next level, we can. So, in patients who have active TB, you first want to know because this is the standard, right? But what if you got that mcoacterial culture, the nucleic acid amplification test, and it showed that they're resistant to rafampen oriniza? Can you give them this? No. And because of that, you need to give different types of drugs. I'm not going to go down that kind of rabbit hole, but I want you to understand that the ripe regimen followed by rafampenizid may not happen for every single patient if they have resistance to those particular drugs. If they don't, great. Ripe regimen, two months. What you do is once you start the ripe regimen, eventually sometime into it, probably around month one and then again later on month two, you're going to test the sputum cultures. You want to see if they're actually starting to clear the miccoacterium. If you do that and you check their sputum cultures and you're again watching out for them and maybe even getting a chest x-ray, you need to know is the actual mcoacterium being cleared. All right. If the mcoacterium uh cultures are still positive consecutively two times in a row and their chest x-ray showed re reactivation TB which means that they have apical cavitation you can't continue rafampen isid for only four months we got to go longer and sometimes we may go seven months we may extend that time frame out so two positive cultures while they're on the ripe regimen and they have reactivation TB initially or they have cavitary lesions you extend it out and it's going to be a total of nine months. So, it's going to be two months of ripe and uh seven months of rafampen and isid. If the cultures are negative, you don't have any chest x-ray with the cavitation or maybe you did, but it doesn't matter because you don't have positive cultures, you can go with the rafampen is it for the four months. That's the way that's taking it just to the extra level is you're going to be checking their sputum cultures and looking at their chest x-ray to see if they have cavitation. positive cultures cavitation extend it an additional time frame and you're going to go a total of nine months so it's two months seven months if they don't have positive cultures maybe the chest x-ray shows cavitation or not doesn't matter because they don't have two positive consecutive cultures you only have to do the rafampeniz for four months all right the only thing I want to add is in patients who have active TB this is talking about pulmonary TV and extra pulmonary TB with just small little exceptions and patients who have TB menitis or they have POTS disease we have to extend it just a little bit longer because this is in some sensitive areas that we have to give established time and penetration of that drug and so sometimes they may be on it for 9 months to an entire year. So that's one other thing I will add. That's the only other little addition for extra pulmonary TB is if it's meningitis or POTS disease, we may have to go a little bit longer than your standard six months. You may have to go 9 to 12 months. The other component here is in TB menitis and TB paricarditis. We have noticed a reduction in neurodeisability from TB menitis and we also noticed a reduction in developing constrictive paricarditis if we added on dexamethasone to their ripe regimen and rafampen is regimen. All right. So that's really important to remember ripe regimen followed by the rafampiniz for the six-month duration that's standard across the board except in TB menitis and pot disease we may go 9 to 12 months and if they have TB menitis and TB paricarditis we'll give them dexamethasone or some kind of steroid to reduce neuro disability and menitis and to reduce the risk of constrictive paricarditis and TB paricarditis. All right, man. We talked about a ton of stuff with uh TB and man, I really hope that you guys feel comfortable after this. I really feel I hope you really feel like you know it and you feel confident and capable of taking on any aspect of it. And if you guys do, you guys know what to do. Hit the like button, comment down the comment section, subscribe, tell other people about it. But I just hope that this got you one step closer to just destroying ### [2:22:05](https://www.youtube.com/watch?v=Qjo9F6Uuca8&t=8525s) Comment, Like, SUBSCRIBE! your exams and doing well and becoming a better provider out there. I love you guys so much. I thank you guys so much more than you'll ever know. And as always, until next time. --- *Источник: https://ekstraktznaniy.ru/video/50421*