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hi I'm Charles prover and I'm working these today we're going to talk about the pathophysiology of tuberculosis that is how tuberculosis makes people sick so in this cartoon there is an infected individual shown on the left and that person is costing or sneezing and all those little small white dogs are particles coming out of the person's mouth and if this person and a person on the right is none unsuspecting individual who is susceptible to infection with T be the person on the left when they cost if they have tuberculosis in their system than some of those bacilli will cost loud and enter the person you're coming into close contact with enter in the droplets and some portion of those infected droplets estimated to be about 10 percent go all the way down the susceptible individuals airway and land in the line they have to be very very small to get to the most distal portion of the lung called the alveoli so they had to be around five or ten microns in diameter once those bacilli have entered the person's lung the host the person's immune system kicks in at the local level and the first part of the immune system to greet these bacilli are macrophages that line the long Airways these macrophages take up the bacilli and within the macrophages the bacilli me reproduce that is increase in numbers the macrophage may then release of the cell I other macrophages will pick them up and eventually one has a number of cells in this disco part of the line that are infected when these macrophages then come together and lung destruction occurs in the mixture of this may end up forming a particular kind of lesion in the lung called a granuloma so I'm granuloma which is often used in the context of tbe infections also called the tuberculosis are a group of macrophages and other inflammatory cells that are the reaction to this TBN vaction once that granuloma becomes large enough for one to see so if a pathologist is looking at the long that is called 8 gonna focus geo H N of course named out there somebody doctor go after the local infection in the macrophages occurs in the granuloma has been formed if the infection is not controlled in at local side there is spillover of the infection to the regional lymph nodes so that allen's knowledge in the lot then those regional lymph nodes have a new reaction and the regional lives knows plus the infected granuloma is referred to as a gone complex and this may be evident on a chest x-ray that a person has done either for routine basis or for whatever reason and radiologists seen this will say oh this looks like a previous infection with tuberculosis and will show later an example of the granule not undergoing complex on radiographs so all of this infection the person who is now infected this is referred to as a primary infection the individual is infected with tuberculosis and for many individuals that's the end of the story the tuberculosis remains in what is referred to as a late and state and remains latent for the person's entire life without causing any problems and they actually get rid of the bacterium so it's not clear if the bacteria are ever completely killed or not there is something of an incident back some nuclear the bacteria from a clinical standpoint one has to assume that once you've been infected with tuberculosis it's with you forever and may cause that's when problems which will speak about the moment so so for ninety percent of people sort of this story ends there however that leads to him about how that 10% so 5% their primary infection is progressive so they go on and they develop a problem shortly after they've been infected with tuberculosis that problem may be represented as local progression of the infection so that long gone focus actually becomes larger and larger and the end up with tuberculosis pneumonia pulmonary disease caused by tuberculosis or they may go on even beyond that the infection may disseminate widely go to many organs in the body most especially the liver other parts of the lung or even into the brain and other organs so that's about five percent of the patients they go on to have local progression or dissemination one pounder and it's been associated with this dissemination and not the only pattern is when the infection heeds multiple organs of the body with tiny little spots that are called military guys are so tiny and this is referred to as miliary tuberculosis and that's most often recognized in the lungs were you seen these little tiny spots all over the lungs that's one form of disseminated infection so that's primary infection and that's five percent now an additional five to ten percent of patients emerged from the late instead of the injection and they develop so-called secondary disease and so not represent a reactivation of prior latent infection or a prior dormant infection and again it's estimated that about 5% of the total population have been infected go on and have this reactivation disease that can happen at any point during your life it can happen that suddenly any point during your lives either within several months of the infection or many many years later and that reactivation is referred to as you as you've written secondary tuberculosis in contrast to primary infection this is secondary infection now the likelihood that somebody may reactivate is actually influenced by many factors including the immune state of the host that is if he hosts the person who's got latent heat day has depressed immunity is officially depressed cell-mediated immunity their likelihood of reactivating can be quite high relatively speaking and some of the immune factors that are most recognized as causing an increased chance of reactivation arco infection with human immunodeficiency virus that's a big one worldwide another is if the individual has received a transplant or is receiving chemotherapy for some other reason for example cancer transplant we're actually giving them immunosuppressant medicine so they don't reject the transplant exactly down there T cells and then they have an increased risk patients who abuse drugs intravenously also are at an increased risk quite a substantial increase risk these groups together each other more than ten fold risk over the general population of reactive haitian their other hosts doctors and also influenced reactivation to a lesser extent they may have two or three fold increased chance of reactivation compared to the general population and that would include patients who are malnourished it would include patients who have diabetes and even patients whose risk factor is only and should say only perhaps that smoking so those can all increase the chance of tuberculosis emerging from its later dormant state and becoming reactivated and what's the increase for HIV transplant drug use W about canceled at least ten fold some of them are actually has 274 that certainly greater than canceled so much secondary tuberculosis is that much of that results from reactivated disease but you can also have secondary tuberculosis because you get infected that means that it's not your only AT&T be reacted in kind of secondary disease that you've been exposed to yet another person infected with tuberculosis and your secondary disease results from that reinfection that new exposure and then once you get that new exposure or the reactivation of your own waiting to be then you can progress sort of done the same pathway of symptoms is exactly you can have local progression as you've indicated or if you're a severely depressed immunologically you may get more of the disseminated infection including military pattern and so forth so just to end like to show the two promised pictures the picture that is all paying is a zoomed in microscopic view of a granuloma and a couple of features to point out first of all in the very middle of this granuloma is very pink very homogeneous material that probably represents dad macrophages and other debris that have eventually been resort and form this dense core sometimes that becomes calcified overtime that may show up on an X-ray such as x-ray picture we show here as a calcified spot a white spot in the long we'll come back to that the other part of the granuloma to point out is this inflammatory reaction occurring around that dance middle and so all of the cells that are shown in the blue here are lymphocytes and monocytes and macrophages and this is the reaction to the infection with the tubercle bacilli sometimes this actually becomes quite necrotic in the center it's not shown so much here and then referred to as key situation because it becomes sort of cottage cheese like the other picture picture of the x-ray shows the calcific granuloma and that would be again your regional granuloma gone focus and it also shows some swelling of the lymph nodes at the edge of the hard and so as previously mentioned this lymph node reaction along with that going focus together make up the gone complex and that is evidence radiographic evidence that this individual has been previously infected with tuberculosis says lately infected at risk for subsequent reactivation