Granulomatous Inflammation: Causes

00:00 So, there it is granuloma.

00:03 An aggregate of activated macrophages, sometimes the macrophages get so activated because of what they're being exposed to, is that they fuse into multinucleated giant cells.

00:14 And we'll see some examples of that.

00:16 Granulomas occur as a consequence of large or persistent antigens.

00:22 So many ways to think about is if you have a very large thing that you can't completely degrade, you called in all your buddies until you've got a big collection of like minded activated macrophages around that persistent antigen.

00:37 And in that case, he may even think of fused multinuclear giant cells as a way to get a big cell that might be able to get its little arms or pseudopods around that big thing.

00:49 Foreign bodies tend to induce granulomas, because they don't go away.

00:54 So an example of this is a non resorbable suture.

00:58 And that gets put in and it doesn't break down and the macrophages keep getting recruited.

01:04 And pretty soon you have a very pretty big collection of them around that foreign body, and we recognize that as a granuloma.

01:11 Certain persistent infections. Fungi and certain bacteria, including, as we'll see, tuberculosis, typically elicit granulomatous inflammation.

01:23 Certain intracellular bacteria, such as TB, specifically elicit granulomas.

01:29 So if a bacteria or a pathogen is particularly tricky, and it lives inside a cell, one of the ways, we may not be able to kill it, it may be very difficult to get out.

01:41 But what we can do is jail it in a collection of activated macrophages.

01:46 And that jailing process creates a large granuloma around a central zone, where the pathogen is kind of corralled in the middle.

01:56 Several autoimmune diseases because it's a persistent stimulation, will develop granulomas.

02:02 And one of the elements of granulomas that you we will want to pay attention to as pathologists is whether there is central caseations.

02:12 So we've talked about caseation necrosis or caseous necrosis, cheesie necrosis, And in the middle of some granulomas, it's so hypoxic, and there's so many toxic metabolites being elaborated.

02:25 And there may be a contribution from whatever's in the middle, that it undergoes big time necrosis, and we recognize that as caseous necrosis.

02:36 The classic caseating granuloma thing is tuberculosis.

02:43 Alright, so foreign body granulomas.

02:45 You can see highlighted by the white arrows, refractile bits of suture material and the suture material just don't go away.

02:54 They are persistent.

02:55 And they will elicit a chronic inflammatory response that recruits over and over and over again, lots of activated macrophages.

03:03 So we have a foreign body granuloma.

03:07 Here's an example of a caseating granuloma.

03:09 So in the same infection, you can have non-caseating granulomas with giant cells.

03:19 Caseating granulomas with or without giant cells.

03:23 They're all just variations on a theme.

03:26 This happens to be a lymph node from a patient who had tuberculosis.

03:31 On the right hand side, we see a collection of activated macrophages, that's that big pink thing, surrounded by a zone of activated T-cells that are releasing all kinds of cytokines, flogging those macrophages to stay there and kind of corral whatever in the middle.

03:47 On the left hand side, we actually see an example of a caseating granuloma same lymph node, same patient, same organism, just variation on a theme.

03:55 And we have that zone, large zone, of larger pinker cells that are the activated macrophages that are forming the granuloma and in the middle, so much toxic insult and somewhat hypoxia that we have central necrosis that we call caseation.

04:11 And that's all it is.

04:12 But recognizing this, we can go, "Hmm, I wonder if this is tuberculosis."