What's up Ninja Nerds? In this video today we're going to be talking about inflammatory bowel disease, also referred to as IBD. We're going to talk about the two phenotypes of it, ulcerative colitis and Crohn's disease. And again, this is a part of our clinical medicine section. If you find these videos and these series helpful, you really understand the topic, you're appreciative of it, show that appreciation. One of the simple ways that you can do that is by hitting the like button, commenting on the comment section, and subscribe. Also, do you want to up your game, do better in your exams, really understand this information? I really think that there is a way that you can do that. You can click down in the description box below. It takes you to our website. On our website we have premium notes, illustrations, quiz questions, all things that I think will really help you that you can do on your own, follow along during the video. All of these things I think will be super helpful in your academic journey. So become a member to access those features. We're even developing courses for a lot of your board exams, so go check that out and much more on the website. Alright, let's talk about IBD. We'll focus on Crohn's disease. What I really want you to be able to differentiate between these is which part of the bowel is involved. What's the pathophysiological mechanism with them being slightly similar, but more particularly the microscopic level of how they're affected? And then what are some causes that we see in both of these, and one simple differentiation factor? All right, let's talk about Crohn's. Crohn's, I think the biggest thing to remember is this thing can affect any part of the GIT. So I could hit the sigmoid colon, I could hit the descending colon, I could hit the transverse colon, I could even hit the ascending colon, and I could hit any part of the small bowel. And so, So what you find, which is really, really interesting out of this, is that it precipitates these skip lesions. So this can occur anywhere. along the GIT. But what's the most common location that you generally see it affecting? It can really occur anywhere. And what we refer to these things here as is we call them skip lesions. It's like the inflammation and these like ulcers that are occurring here are skipping around the actual GIT because this can occur in the mouth, it can occur in the small bowel, large bowel, all over the place. But the most common area that's usually affected here is by far the ileum. So the ileum is going to be by far the most common area that is plagued by Crohn's disease. One of the areas that happens to be spared, thankfully, I guess in these ways that you can think about it, but it also helps to make differentiation between ulcerative colitis, is for the most part the rectum is relatively spared. You don't get a lot of like disease there. You do get anal disease like perianal diseases, but for the most part the rectum is spared. So when someone asks you, tell me the parts of the bowel that's affected by Crohn's, you can say any part of the GIT. It kind of skips around throughout the GIT, but it most often hits the ileum and it spares the rectum. That's what I would want you to tell them. Now, whenever they say, what's the classic findings? We'll make more sense of it as we go along, but there's crazy inflammation at different parts of the GIT, but most often the small bowel. The small bowel is really important for absorptive functions. And so whatever happens here is you actually kind of damage this, you get decreased absorption, you get a lot of osmotic kind of pulling, and these patients oftentimes get diarrhea because they don't absorb things, and the undigested material that they don't absorb, they kind of yank into the actual GI lumen. And so oftentimes these patients will get a diarrhea. So some of the classic findings that these patients will kind of experience is diarrhea. But I think the big thing to remember here is that it's non-bloody. That's a really, really important one to remember. So oftentimes they will have a diarrhea, but it's more of a watery diarrhea. Okay. The other thing is what's the most common location that it affects? The ileum. So when it causes inflammation of the ileum, where would the ileum be most commonly? Well, it kind of connects right to your kind of your cecum, which is on the right lower quadrant. So oftentimes these patients most likely experience right lower quadrant pain. And so if you see a patient with right lower quadrant pain and diarrhea, which is usually non-bloody, I would definitely take some time to think that this could be a patient with Crohn's disease, especially if it's kind of occurring in what we call these relapsing, remitting types of patterns. In other words, patients will have a flare-up, they'll experience these symptoms, potential complications that we'll talk about, and then what happens is their immune system settles down, it kind of heals the bowel, they have no symptoms, and they'll have another flare-up. And so it constantly occurs in these flare-ups, or what we call relapses, where they have injury, and remission, where they kind of like settle down in their bowel wall. Let's kind of take a little bit more of a deeper look. So if I were to actually take a look at this lesion here and I zoom in on it, what's actually happening at the microscopic level if I were to kind of take some time to look at that? Well, what we actually see here is that there is definitely tons and tons of inflammation in this particular location. And what we get is we get this nasty little ulcer. I've eaten through tissue. You got to remember some of your anatomy. If I eat through the epithelial, the lamina propria, and the muscularis mucosa, I've eaten through the mucosa. If I eat through this blue connective tissue with glands, I've eaten through the submucosa. If I've eaten through the layers of the muscle in the outer part, the muscularis externa, I've eaten through that. And I've gone through almost the entire wall of the alimentary canal in this part of this portion. And so what we refer to this as, is we call this a transmural ulcer. So this is a transmural ulcer, meaning that the ulcer has involved almost all of the actual walls of the alimentary canal or that GI tissue at that point. The other thing that we see is that if we were to take a look under the microscope, all this inflammation, there's these areas that contain tons and tons of immune system cells, lymphocytes, macrophages, dendritic cells, all these things kind of clumped into this area of inflammatory tissue. And these kind of clumped up together parts of you know cells and debris we call this a granuloma. And granulomas are also extremely common in patients who have Crohn's disease because it's just a lot of inflammatory cells kind of aggregating in this transmural ulcers. So whenever you have lots of transmural ulcers, lots of granulomas at the microscopic level, think Crohn's, the question is is why do we have transmural ulcers and granulomas? One of the reasons why is there's some type of immune dysregulation. And I think that's really the best way of describing it because it's still not really known. There's a lot of hypotheses as to how this occurs. And I don't want you guys to get too tied up in it. I want you to understand it with respect to the treatment process that we use. So there's some type of trigger and these triggers usually affect these cells. In Crohn's disease, it's oftentimes what's called the Th1 cells. I don't want to get too bogged down, but what I want you to know is that these cells release lots of cytokines. And some of them that I think are pertinent to remember is going to be things like TNF alpha and interferon gamma. But I would really focus on the TNF alpha. And the whole concept of these is that these really are kind of released into this area. So I'm going to kind of bring them in here. And what they do is they propagate inflammation. So they bring lots of immune system cells and all different types of white blood cells to the area to kind of cause, unfortunately, an undesirable inflammation. And that inflammation over time leads to erosion and destruction of the actual GI wall. So that's one thing that we can talk about. And the reason why I wanted to mention that is we have drugs that we actually give to block TNF-alpha. The other ones that we also should know are related to the Th1 cell. It releases cytokines that actually directly stimulate these other cells. And these cells, we don't really know how they exactly do this, but these are called Th17 cells and they induce a lot of badness. The cytokines that may induce this stimulation are also important because we use them in the treatment. And these are going to be things like interleukin-12 and interleukin-23. And we have drugs that block these. But what they do is they stimulate the formation of Th17 cells and then more of these Th1 cells, which propagates more inflammation. TH17 cells, what we've been hypothesized that they do is they stimulate an upregulation in neutrophils. And you gotta know what neutrophils do. They're like little eaters and they really love inflammation. What do you think they're gonna do? They're gonna go to this area and they're really going to jack up the inflammation. So you get the point here that there's lots of inflammation going on. But the culprits that seem to be occurring here are these Th1 cells and these Th17 cells via these different cytokines. And that cytokine that I actually should have here that stimulates this, I apologize, we don't have a drug yet for this one, but it's called interleukin 17. Okay? Now, with that being said, I think some of these are really important to be able to remember, especially these and TNF Alpha because we have drugs for them. The question then comes, what's causing all this crazy immune dysregulation? What's causing all these ulcers? It comes down to things that we still don't really know. And that's why this disease is so frustrating in the sense that there's not a lot of data. But what we do think is there's two genetic factors because we think it's autoimmune. And oftentimes autoimmune is where your immune system goes haywire and generates undesired inflammatory reactions that destroy your own tissue. And it's usually always connected to a genetic and environmental factor. Genetic may be the fact that these patients have a family history of IBD. And I think that's always important to ask within your history. The second one is that there may be something that's causing a mutation in genes that hyperactivate this immune system. And the ones that have been associated with this, I don't want you to get too bogged down in it, but this is more of your, you know, USMLE step one stuff. But there is a mutation in the NOD2 gene that may just upregulate this thing and just cause this cell to become hyperactive. Okay? But this cell is now already a little bit hyperactive. What's the stimulus that's going to hit these receptors and say, hey, start pumping out cytokines? Believe it or not, we don't really know. We have assumptions. It could be NSAIDs. It could be all these different things. I think one of the two big things is the Western diets. They happen to be, unfortunately, more of a really big trigger. Whatever it may be in that diet, these may be a really big trigger for these immune system cells. What's interesting is smoking. And I want to talk about this with UC as well. But smoking has been shown to increase... the risk of a lot of Crohn's disease flare-ups. Okay. And I think that's really important. And the reason why is we'll talk about this in a little bit. UC has been shown that smoking decreases UC flare-ups, which is really interesting. But now we have a little bit of an idea here, right? So Crohn's, right lower quadrant pain, non-bloody diarrhea, ileum most commonly involved, rectum spared, transmural ulcers with granulomas, immune dysregulation by... Th1, Th17 cells, primary cytokines is interleukin 12, 23, TNF alpha. They really propagate a lot of inflammation. Causes? Likely autoimmune to some degree. We just don't know the exact kind of factors there. We have suspicions. But the big one to remember there is smoking really increases the risk of this flare-up. What about UC? So UC is interesting and I think this is also kind of cool in the sense that this one stays in the colon. it stays in the colon. So it only affects the large intestine. It never branches into the small intestine. What happens though is that it's Crohn's disease. It started one place, flipped around, went all over the place. You see, it usually starts at the rectum. What doesn't affect the rectum? Crohn's. And then what it does is it causes continuous or contiguous inflammation that can spread and spread and spread throughout the entire colon. And so what I want you to remember is that oftentimes this could start in the rectum. go up the sigmoid colon, go up the descending colon, cross over to the transverse colon, and then move down the ascending colon into the cecum. If it involves the entire colon, it's called pancolitis, right? Oftentimes though, it usually will just hit more of the rectum and the sigmoid. But the big thing to know is it always starts at the rectum. And then it moves continuously. or contiguously throughout the colon. So it can start at the rectum and then move in that particular process. One of the big things to remember is because it causes these nasty kind of lesions in the distal part of the colon, you can definitely cause blood to come into the actual stool. And so oftentimes these patients will have kind of a bloody-ish stool. We call that hematocesia. All right, so this can cause... hematochesia and it may be a little bit even more of a bloody ish diarrhea as well so you may see hematochesia or you may see more of a bloody diarrhea all right so or we'll put bloody diarrhea so i would watch out for that the also other thing i want you to remember is where does it always start the rectum it can hit the sigmoid colon as well but if it's always in that area what quadrant would that be in left lower And so in that particular sense, since it's really always starting here, it's going to most likely cause left lower quadrant pain. Okay? The last thing is whenever you hit the rectum, the rectum is involved in contractions that are supposed to help you to evacuate your bowels and then make you feel like you evacuated them. So sometimes whenever you inflame the rectum and you affect its motility, It can lead to this sensation of you have to poop, but you never feel like you actually completely do finish or evacuate your bowels. And so in this sense, we call this. Tenesmus. And I think this is a really high yield buzzword term to associate with ulcerative colitis. So rectum involvement always contiguously starts from there and moves throughout the colon. Since it starts at the rectum, it's usually always left lower quadrant. Does cause lesions that can lead to bloody diarrhea or hematocesia. And tenesmus because it does involve the rectum, that incomplete sensation of emptying their bowels. Okay, with that being said, I think this is really, really important to remember. This is really important to remember. And then finally, this is important to remember. The next thing I want you guys to understand here is what is the pathophysiology behind us developing these lesions? So again, if I do the same thing I did up there where I take a piece of tissue here and I kind of say, I'm going to zoom in on this and I'm going to look at this in great detail. What is happening here? And so what you're noticing here is you are noticing inflammation, but look where it only extends to. It only extends just above the muscularis externa. So it involves the mucosa and the submucosa. So in this particular sense, there is what we call submucosal ulcers. and there is no granulomas. There is no particular granulomas or collection of inflammatory cells that are aggregating into that inflammatory material. So I want you guys to remember that because that'll help you, I think, in differentiating these two. So you're going to have no granulomas. The question then arises, if there's no amounts of T cells and lymphocytes that are really kind of aggregating in this area, what's triggering a lot of this ulceration and inflammation? It's immune dysregulation. It's the same concept that we've talked about above. The thing is with ulcerative colitis, it's a different set of cells, but for the most part, somewhat of the similar cytokines. And the primary cell that has been linked to this one is Th2 cells. And there may be in some degree Th17 cells, but they're so minute and I don't want you to confuse it with Crohn's. So stick with Th17 for Crohn's and only really Th2 cells in ulcerative colitis just to keep it easier in your brain. What we have seen with this guy is he'll release kind of a couple different types of cytokines. And I don't think all of these are important to remember, but I think this one is important to remember. and I think it's this TNF alpha factor. There's lots of this guy. And this TNF alpha really likes to propagate inflammation. So it really wants to inflame and kind of pull a lot of different types of immune system cells into the area to start destroying some of that tissue, unfortunately. There is other cytokines. I don't want you to get too bogged down with these. Things like interleukin-4, interleukin-5, these may just activate like... eosinophils, and they may activate B cells, which again, all these really do is propagate kind of more inflammation in that same sense. But I don't think that these are going to be important because we don't really have any drugs that really hit these. And there are other ones like interleukin-13 and that causes lots of mucus production. I think that is kind of helpful to remember because these patients with UC do have a lot more of a mucus kind of like containing stool than you would see in a Crohn's disease patient. But I think the big factor to remember here is this cytokine, TNF-alpha. And that's why oftentimes in ulcerative colitis, we usually give a particular drug to block these, like infliximab. Again, there is other cytokines like the maybe some degree interleukin 1223, but they're not going to be the big ones. This is the big one. Question to ask yourself is what's causing this. It's the same concept. This cell is just a little bit more hyperactive and ready to release cytokines that are unfortunately going to cause badness and inflammation. The question is, what are those things? I think it's the same concept. You really should have some type of genetic component, like a family history of IBD, or a genetic mutation in an allele. And usually this is where you have your HLA mutation. There's a bunch of different types of HLAs. DRB1 may be more linked to this one if you really want to remember that one, but I don't think it's really worth the squeeze memorizing that, to be honest with you. But... This is worth at least remembering that this is causing the cell to become hyperactive. The question is what's going to stimulate it to trigger this inflammatory response? And it's usually an environmental agent of some sort. Now, this is where I kind of want you guys to kind of take some time to understand here. It's the same thing. A Western diet has been shown to be a really big trigger. But here's the interesting thing. Smoking, in some way, shape, or form, has been shown to decrease, in this particular scenario in comparison to Crohn's, to decrease UC flares. Now, by no means, if you are a patient who has ulcerative colitis, am I telling you to smoke cigarettes because you'll have less flares, but it has been shown that smoking can decrease UC flares. How exactly does that? We don't know. When it comes down to it, I really want you guys to understand the really microscopic small level of how this is being affected, the overall large and kind of like macroscopic view, and then knowing that there is a lot of immune dysregulation here. Having an idea of the cytokines that are involved, I think is a really important thing when it comes to pharmacology. Now, let's talk about the complications. All right, my friends, so now we're going to move on to the complications of inflammatory bowel disease, particularly with Crohn's disease and ulcerative colitis. So In this patient who has Crohn's disease, we already know that they can primarily have ileal involvement with right lower quadrant pain and more of a watery non-bloody diarrhea because they're involving that area of the small intestine, which is important with absorption. I think the other thing that you really have to be able to identify is in a patient who has Crohn's disease, what are the potential complications that you need to be aware of and how to identify them? So the first one is a little bit more of a chronic finding that you can see. So with more relapses of the patient experiences, more flares that they develop because of that massive inflammation. What are some of the things that you'll see? One is malabsorption. This is a really big one. And I think the concept behind this is that if you hit the ilium, right? You're hitting the ilium. The ilium is really, really crucial to this. Because the ilium is actually being hit, this is an area of massive absorption. And so you have to think about that. Let's say the first thing that we think about is fat malabsorption. So here we have some fat particles, and here we're kind of zooming in on this ileum here. We're really zooming in on that portion of the bowel. And you can see how there's lots of inflammation and erosions in that ileum. One of the things that happens here is that whenever the fat isn't absorbed, this isn't going to happen here, you develop a lot of complications. What are some of the complications here? One of the big ones is, is that whenever you have decreased fat, we'll actually put this down here, decreased fat absorption, one really profound effect here is that you don't absorb with it fat-soluble vitamins. And so one really big problematic issue here is these patients will have decreases in the levels of particular vitamins that they don't absorb with that fat, such as vitamins. in the following order, A, D, E, and K. So there can be deficiencies in each one of these vitamins. Vitamin A, usually these patients develop night blindness. Think about eyes. D, it's important with calcium. So they develop hypocalcemia, which kind of sucks calcium from the bones so they can develop osteomalacia as they're older or rickets when they're younger. E, important for nerve function and also for red blood cell function so they can develop neuropathy and hemolytic anemias. And then K, important for bleeding. So it's important to make coagulation proteins from the liver. And if you don't have K, you don't make those coagulation proteins and the patients bleed. So watch out for fat-soluble vitamin deficiencies. The other thing here, which is kind of really interesting, is that you have less fat that's being absorbed. More fat enters into the stool. And so more of this fat entering into the stool, when this really is rich in the stool, this causes the stools to become really foul smelling, really greasy. And we call this steatorrhea. So I want you to watch out for fat, greasy, foul-smelling kinds of stools, along with fat-soluble vitamin deficiencies. The next thing that's really kind of interesting here is when you don't absorb fats, what happens is fats are supposed to bind. What happens is fats really love this molecule called oxalate. So imagine here I have a fat molecule. And it loves to bind with this other molecule called calcium. And so when it binds with calcium, that leaves this other molecule free. And this other molecule that's free, which we're gonna represent here in pink, is gonna be called oxalate. So if there's lots of fats that stay in the bowel, they bind up calcium and they leave lots and lots and lots of this free oxalate molecule on its own. Oxalate can then get increasingly, it can have a lot of absorption. So here, we're just going to write here in this pink here, oxalate. There's going to be lots of this molecule that's going to be present getting absorbed. Whenever there's increases in oxalate, This is a problematic molecule because when it gets filtered across the kidney tubules, it likes to bind with any calcium in the kidney tubules. And what it'll do is, is it'll increase the formation of calcium oxalate stones. So these patients also have increasing incidence of nephrolithiasis. Okay, so they can have kidney stones. That's a terrible scenario. What else could be a problematic issue here? The other thing is not just fat. Obviously, if you're not absorbing fat, you can experience weight loss as well. If you're not absorbing fat, I think the other thing that you want to watch out for in these patients over time is a weight decrease. Watch for weight decrease, steatorrhea, fat-soluble vitamin deficiencies, increasing risk of nephrolithiasis. What else? Well, the other thing is you absorb micronutrients like B12. B12 is a really, really big one here. So B12, if it's not properly absorbed because it's super, super highly absorbed, fats are always absorbed in the ileum, B12 heavily absorbed in the ileum. So now if you don't get this absorbed, this decreasing amounts of B12, whenever there's less B12 in the bone marrow, this is a really problematic issue because now red blood cells don't have the time to mature. And if they don't mature because of a lack of B12, you don't produce enough of these functional red blood cells. And so we call this anemia. It's more of a macrocytic anemia, but you can see microcytic anemia as well because sometimes iron deficiency can also occur. So I don't want to write down macrocytic because you can see both. I just want you to remember, look for a drop in the red blood cells. The last one, I think this is probably the most interesting, is bile acids. Bile acids are heavily absorbed in the ileum. And so if you have disease here, you won't be able to absorb them. They're naturally absorbed, they get taken to the portal circulation, back to the liver, and the liver just recycles it and puts it back into the bile. If for whatever reason I don't absorb these, because I'm not absorbing B12, I'm not absorbing fat, if I don't absorb the bile acids, why is that a problem? So what happens is there's decreased bile acids. in the bile because this is supposed to go back to the liver and be recycled into the bile. When there's less bile acids you leave an imbalance between cholesterol and bile acids which are two big components in the bile. Whenever there's overpowering amounts of cholesterol within the bile this leads to an increased formation of cholesterol containing gallstones which is the most common type of gallstone we've talked about that. So now, this leads to cholelithiasis, stones that can form within the gallbladder. And what's the problem with this? It can get stuck in the cystic duct and cause cholecystitis. It can get stuck in the common bile duct and cause kind of problem there, cholelithiasis. And the most concerning was an infection that arises proximal to that stone, like ascending cholangitis. So you can see a lot of complications associated with cholelithiasis. Okay, so increased risk of gallstones, kidney stones, fat, kind of containing stools, vitamin deficiencies and anemia along with weight loss. Pretty problematic stuff. The next thing I want you guys to think about is fistulas and abscesses. This is a super common one. So this can really affect two areas. I want you to remember the anus and again the ilium. But remember about Crohn's disease, it can skip around anywhere. So if it wanted to it could hit the colon. at any part, right? What happens is, is when these lesions occur, remember I told you they're transmural? And so they eat almost completely all the way through the bowel wall. So if you guys remember, again, back into this kind of component here, we said that if we were to kind of have a little bit of this bowel wall here and we went through all the layers, we would kind of go almost all the way down until we got to what? To this last outer layer here called the serosa, right? Problem is that when I do that, I can create these little tracks that connect and form a tract between other organs nearby. So what if I form a tract that actually occurs between the bowel and the actual bladder? This is called an enterovesicle fistula. And the problem with this is literally what it sounds like, things like bacteria. and feces and air can leak right from the bowel into the bladder. And so obviously you can imagine if I have lots of fecal material and bacteria, what am I at high risk of? UTIs, right? So there's definitely an increased incidence of UTIs. If you see this, I think this is also could be helpful to consider. Sometimes they use this terminology that when you hear a fizzing type of sound in your urine, whenever... they're peeing it could be evidence of air that's leaked into the urine and they call that pneumaturia and then if you were to literally test their urine it'd be rich in fecal matter so they would also have what's called fecal urea so I think it's important to watch out here for pneumaturia and fecal urea associated with enterovesicle vesicle fistulas but oftentimes they just come in with recurrent UTIs Another one is it can actually occur between the bowels. So this one is often what we refer to as if I kind of fistulize between two parts of the bowel here that are really, really inflamed and they connect to one another. This one's interesting. There's not a lot of presentations, but it could be an entero. enteric fistula. And often times the problematic issue is if you, let's say that you have material that's supposed to be going, getting absorbed down this way, and then all of a sudden just bypasses here, you're bypassing an area of absorption. So if you don't absorb things, what happens? You end up with diarrhea. So I think one thing to watch out for is if they have increasing incidences of diarrhea, but sometimes it can be difficult to sift out during a flare. The next concept, and I say this is really one that is super obvious, is this can happen especially with the bowels near the skin. This often happens near the anus. So this is usually the most common location is usually near the anus, because I told you, these erosions love to occur at the anus as well. So sometimes there's skin near the anus, and what happens is that this will literally form a tract that will fuse with the skin. And now, material, literally, I'm not kidding, any kind of fecal material or bacteria here can easily, let's actually draw some fecal material here, can easily drain out, right out via the anal area. This one, this type of fistula here is called enterocutaneous, because it's between the bowel and the skin. And I think the biggest thing to watch out for here is two particular findings. One is literally what it would sound like. Any drainage. Do you notice any drainage that is occurring near the actual anus? And usually that's one particular thing. Or do you notice any redness around the skin that's kind of weird? The scary complication that can arise though is that these fistulas can create an opportunity for any kind of bacteria though that are in this kind of area to kind of come out here and organize. and form a nasty little abscess. And so I think this is one of the most concerning complications is these perianal abscesses. And obviously this is going to be pain within the anal area. So it's kind of straightforward. You're looking for a palpable mass outside of the anus. It looks warm. It looks erythematous, right? And on top of that, maybe there's some drainage, but you're definitely going to notice a lot of swelling and a mass that's going to be present around the anus. And that could be a perianal abscess. All right, so we talked about fistulas and then abscesses. Out of all of these, the most common one that I think is really important to remember is going to be the interovesicular fistula. In other words, it's the most common you'll be tested on. The next one is I want to quickly go by because it doesn't happen that often. It's not too common to cause any symptoms. You may just have them and never have any particular symptoms about them. But because the ileum is the most commonly affected area, sometimes it can become so inflamed and so fibrotic that it can narrow the component where any kind of material, like intestinal material, is supposed to go into the large intestine. It can be obstructed at that point. And so since the ileum around that ileocecal junction is the most common here, sometimes if we were to kind of zoom in here, it's super, super narrow. And so what this can do is, is this can create a difficult time for... particular materials to move through. the actual GIT. It usually doesn't cause a complete obstruction. It's more likely to cause more of a partial obstruction. But I think nonetheless, if these patients do develop an obstruction that's involving the small bowel, so I'd watch out for what's called a SBO, small bowel obstruction. And oftentimes, if you guys remember that mnemonic that we talked about, they present with the CAVO findings, right? So cramping, abdominal pain, abdominal distension, vomiting. Obstipation. I wouldn't really potentially see this part because it's usually only more in a complete bowel obstruction. But if it's bad enough, it could potentially be findings there. So definitely watch out for increased incidence of SBO in patients with underlying Crohn's disease. Okay, that talks about Crohn's disease with effects on the intestinal system that it has directly. What about the effects that it has more particularly within the realm of ulcerative colitis? So in patients who have ulcerative colitis, again, I think there's really just one big thing that you have to be able to recognize. Tons of stuff for Crohn's, which is frustrating, but one big one for ulcerative colitis. And that's colitis and megacolon. I've told you before, usually this always starts at the rectum and it'll continue to contiguously or continuously spread throughout the actual colon. It goes rectum, sigmoid. descending colon and then it may work up into the transverse. So it'll cause massive inflammation here. And so I think one of the big things with this massive colitis here is you're obviously going to have increasing pain, you're going to have fevers, and you may even have an increasing white count, especially during these really, really bad flares. And so I'd watch out for increased pain, increasing fevers, and increasing white cell counts. So increasing pain, fevers, and white blood cell counts, right? The other thing I would watch out is whenever you have massive colitis here, you don't absorb things very well, especially water. And on top of that, when it's super, super inflamed, which you get an ulcerative colitis, they often have a lot of blood within their stool. And so sometimes they'll have an increase in their bloody stools. So you know how it's like, oh, you know, these patients with colitis have bloody stools. How am I supposed to recognize the difference? There'll be an increase in their bloody stool output. So watch out for an increase. and stool frequency, but also look for more bloody stools. So if you notice that they're having more bloody stools than usual, and on top of that, they're having systemic symptoms like increasing pain, fever, and leukocytosis, be concerned that they may have a colitis that's actually developing that's becoming more extensive. The fear of this is that if this continues, this can progress to megacolon. And that's the scary thing, is that this inflamed area. angry colon, usually the distal parts, usually sigmoid, usually the descending colon, they become so inflamed. And what happens is this inflammation literally shuts down the nerves and the muscles from contracting. And so you have a massive decrease or absence if you will of motility in the large intestine. The problem with that is you don't move things along and if you don't move things along pressure starts to build up. And as pressure starts to build up on top of that if you're not having movement you'll have dilation and pressure. So what we say is at this point if the dilation here is greater than 6 centimeters, we now have a super dilated colon. And if we have a super dilated colon in combination with all the findings of colitis, so plus fevers, pain, and a leukocytosis, this 100% most certainly suggests that this patient probably has a megacolon that's starting to develop. One of the other things that they'll still have is diarrhea. So they'll still have potentially some bloody diarrhea. But I think the biggest concern here is with these patients is that the big difference is the size of the colon because of no motility from massive inflammation. But the last thing that is the most scary complication, which you can see, is as this thing continues to dilate and dilate and dilate, the pressure can build up. And these patients can start to have an increased risk of, what do we call this, a perforation. So they can develop a bowel perforation. And so I think that's usually... By far, in this particular scenario, the most concerning risk factor associated with ulcerative colitis is perforation. which they can start developing peritoneal findings, secondary to a toxic megacolon. All right, so these would be the big things that I want you guys to remember and consider in a patient with ulcerative colitis is increasing pain, fevers, white blood cell count, more bloody stools, can progress to a dilated colon that if it gets greater than six centimeters, now we're at toxic, and if it perfs, you can develop a perforation which can lead to peritonitis. The last thing I wanna talk about is cancer risk. This is usually, ...more particularly associated with ulcerative colitis. And I think it's pretty straightforward. Think about it. What does Crohn's disease usually spare? The rectum. And it skips around. It can hit the colon, but it's more commonly going to involve the ileum. What always involves the rectum and spreads up through the colon? Ulcerative colitis. And so oftentimes these patients, when they have constant flares of their ulcerative colitis and inflammation... What happens is chronic inflammation is a recipe for dysplasia, which is a recipe for cancer. And so because of this, these patients are super, super high risk for neoplastic transformation. And they can have a super high risk of colorectal cancer. So their colorectal cancer risk goes up massively because of the chronic inflammation, which creates a recipe for dysplasia and increasing risk of tumors. So oftentimes these patients in Crohn's disease, but I'd say it's much higher risk in UC, have to be constantly surveyed for the increased risk of colorectal cancer. All right, as if that wasn't enough, I know it's a lot, just hang in there with me a little bit longer. These are the intestinal complications. More particularly, this is something else that will help you to think that it could be IBD in general. So if a patient has... pain, diarrhea, or they have pain, bloody diarrhea, tenesmus, they have some of these potential complications. But more importantly, they present with some extra intestinal features because of systemic inflammation that occurs in this disease. It could make you think about IBD. One thing is it loves to hit the joints and inflame the joints. And so I would naturally just try to look for any kind of arthralgias. So this could pertain to the joints. So you may have knee pain, elbow pain, or it really loves to hit the spine. And so oftentimes these patients can have associated like spondylitis, and that's a really, really big, or sacroiliitis. So watch out for that one. The other thing is it loves the eye, loves to inflame the uvea. And so I'd watch out for uveitis. Usually these patients present with a red eye and eye pain. Another one is it loves the skin and it causes some lesions that occur of the skin. I'll show you guys a picture of these. One is it can cause this nasty necrotic skin lesion called Pioderma gangrenosum. And another one is it can cause these like red nodules to type of kind of like these like subcutaneous nodules to form and they're kind of like really big bumps. This is called erythema nodosum. So remember, pyoderma gangrenosum and erythema nodosum are two skin findings to remember. I'm just going to put down here because we're going to have those pop up, the skin findings. Also, I don't want to spell the pyoderma gangrenosum. So next thing here is This is a systemic inflammation. Systemic inflammation that is chronic rather than acute, when it's chronic it increases the formation of coagulation, procoagulants. So you kind of throw off your coagulation cascade. And so because of this, these patients are super high risk because of the chronic inflammation for DVTs. So they can get DVTs because of hypercoagulability, we'll write that down in a second, but the complication that can arise from a DVT is these can pop off, they can move into the right side of the heart. And then they can go and get stuck within a pulmonary vessel and cause a pulmonary embolism. All right. They also can cause arterial clots, but it's way more common for them to affect the venous system. And the concept behind this causing what we call VTE, venous thromboembolism, DVTPE, is because these patients have hypercoagulability because of inflammation. Okay. Hypercoagulability. Now, that's because of the chronic inflammation. The last one that I have to hit here is called, and we talked about a little bit in the cholangitis lecture, is called primary sclerosing cholangitis. This is when there is inflammation of the intrahepatic ducts and inflammation of the extra hepatic ducts. This is very, very highly associated. More particularly, if you have PSC, it's likely that you have UC. If you have UC, there's a chance that you could have PSC. And so it's really important to understand that relationship. And so in patients who have PSC, they likely also have UC. So look for features that they have in PSC, jaundice, pruritus, and increasing risk of cirrhosis. But again, I think that this is a really, really big one to remember. and it's primarily only associated with, only with ulcerative colitis, not Crohn's disease. Okay. All right, my friends, lots and lots of complications that are associated with IBD. I know it's a lot. Take some time, go through this a couple of times and really get it. Now let's move into the behemoth, which is going over the diagnostic approach. All right. That's a lot. Now what we have to do is try to put all of this together and think about if a patient has Crohn's disease or ulcerative colitis. So the first thing I want you to think about is kind of try to localize where they're having pain. Is it right lower quadrant? That suggests more Crohn's. Is it more of a watery diarrhea? That suggests that it's probably involving the ileum, which is the most common location. The other thing is look for extra intestinal disease. Look for anterior uveitis, erythema nodosum, pyoderma gangrenosum. Look for potentially some potential manifestations of patients developing VTEs. So have they had DVT? Have they had PEs? those are definitely important to remember. And also think, do they have potential history where they had complications associated with this? Have they had a weird history of perianal abscesses? Have they had lots of bowel obstructions? Have they had potentially kidney stones and gallstones? These are things that should start making you think about that. Weird vitamin deficiencies and really fatty appearing stools makes you think about that. So I'm thinking Crohn's, right, based on this. Well then how do I go about determining if it is? First thing is some patients will get what's called a barium small bowel follow through. and basically you have them drink the barium, and you allow for it to move through the esophagus, the stomach, and then start moving through the small intestine. And what you look for is you look for these areas where there's just a very significant amount of inflammation, and where the colon looks really, really like, or in this case, I'm sorry, the ileum looks really, really thin. And these could be evidence potentially of a string sign here, where you're not having a very happy appearing type of ileum. It's really inflamed, and you're forming some of these like strictures or narrowing, due to a lot of inflammation that's occurring within the mucosa, submucosa, muscularis externa, and that could be indicative of a lot of inflammation here that's narrowing the lumen. All right, problem is it's not super, super specific. It's not going to guarantee you the diagnosis, but a string sign could definitely be supportive. The thing that is the most diagnostic test is an ileocolonoscopy with a biopsy. In other words, you have to go through the anus, up through the rectum, up through the sigmoid colon, descending, transverse, down the ascending colon, and then eventually through the sigm and then go into the ilium and then peak into the ilium. When you do this, you're looking for lesions. And oftentimes they present in a skip-like fashion, meaning that you may see some in the colon here in the descending, maybe a little bit in the transverse, maybe a little bit in the ascending, and then maybe a little bit in the ilium. It's not a continuous lesion. The other thing is that it usually has this weird like cobblestoning appearance. You see this? This is a terrible type of like inner looking mucosa. And this is super suggestive of a patient having Crohn's disease. The other thing is, if you took a biopsy and you look at it, you'd be able to see that the ulcer extended all the way through mucosa, submucosa, and potentially into the muscularis externa. And then on top of that, if you took a biopsy, you may even be able to see granulomas that would be suggestive and diagnostic of CD. So again, this is definitely the way that you want to go about diagnosing it. This may just help and add some supportive nature to the diagnosis. The thing that you have to ask yourself is, okay, I can diagnose a patient with Crohn's disease based off an ileocolonoscopy or biopsy. How do I know if they're having a flare-up of it? Because some patients can go into complete remission and not have any issues. Well, CD flare-up is really important to identify. And so things that you should look for is an abdominal x-ray, all right? A fecal calprotectin, maybe even an ESR and a CRP, and a stool culture, an ova and parasite culture, and a C. diff assay. I'll go through it. First thing is the abdominal x-ray. I want to see if there's any dilated bowel loops. You're like, wait, what? Okay. Why? Well, I want to see air fluid levels. Doesn't that bowel obstruction? Yeah, because guess what? And patients who are having a seedy flare, oftentimes they have so much inflammation of their ileum that they cause small bowel obstruction. So you want to rule out, are they having any small bowel obstruction? The other thing is I want to check a fecal calprotectin level, an ESR and a CRP. You want Because sometimes patients will present with this watery diarrhea and pain, and it may be hard to say, is this IBS or is this IBD? I don't really know. So oftentimes what we do is we check a fecal calprotectin level, and if it's super elevated in combination with ER, SAR, and CRP, it more likely suggests an IBD flare-up rather than IBS. And so that's really helpful in this scenario. The last thing is that in patients who come in with pain, watery diarrhea, they look really ill, you definitely want to rule out an infectious etiology like gastroenteritis. you know, some type of weird parasitic gastroenteritis or even C. diff. And so sending off the stool culture will rule out things like salmonella, Yersinia, Shigella, you know, E. coli, etc. Oven parasites will rule out things like Giardia, right? And then C. diff assay will rule out C. diff. And so if all that's negative, it rules out some type of nasty gastroenteritis and helps to kind of maybe say that this definitely could be a flare up of their Crohn's disease. And it's really important to identify these particular scenarios. Now, I go to the other arm here and I say, okay, a patient comes in with left lower quadrant pain. They come in with hematocesia, so bright red blood per rectum. And they have that tenesmus, which is that pain that kind of triggers them to have to have an urgency to go to the bathroom. And so they go to the bathroom. and then they feel a little bit better. All right. So that's kind of that picture that we would see here with what ulcerative colitis. If you add to the mix that they have extra intestinal disease, anterior uveitis, enterobatic arthritis, pyoderma gangrenosum, erythema nodosum, maybe VTE, PSC. These are things that can be helpful and say that's likely ulcerative colitis. But how do I really determine this? Well, one way is you can do a barium enema. Big thing, never do a barium enema if a patient you suspect has toxic megacolon. So if you get an abdominal x-ray and you say, oh my gosh, their colon is super dilated. It's greater than six centimeters and they have fever. They have leukocytosis. I better not do a barium enema because you can increase the risk of perforation because you're pushing in by via pressure is barium. So a barium enema is good if the patient is not in an active kind of like super bad flare up of UC and they don't have any kind of concern for toxic megacolon. If you do this, what you'll notice is it's like a pipe. There's like, you can't even. and see the haustra. And so these patients lose their haustra and they develop what's called a lead pipe sign on their barium enema, which is very supportive of UC, but it's not completely diagnostic. What is the most diagnostic test is to attain a colonoscopy because then I'll visualize all the lesions. I'll go in and I will see a very friable colonic mucosa that looks just like this. But even more helpful is I can see this from the rectum going up into the colon. How far it extends doesn't really matter. If it's continuous rectum sigmoid descending, that really adds to the utility that it's likely ulcerative colitis. Then, if I take a biopsy and I see that the ulcers that they have are only extending to the submucosa, there's no granulomas, maybe there's some intestinal crypts that are present, that really seems suggestive and diagnostic of ulcerative colitis rather than Crohn's. Then you say, okay, I have a patient who comes in, I see all of these lesions, I definitely think that it's ulcerative colitis. How do I know? it's not a UC flare-up that they're having, versus if is it toxic megacolon, do they have any concerns for toxic megacolon right now? Well, I probably should get an abdominal x-ray. How do I know it's not ulcerative colitis versus IBS? Get a fecal calprotectin, ESR-CRP. And how do I know it's not infectious diarrhea? potentially. Well, I probably should get a stool culture, you know, ova and parasite and C. diff assay. If I see a dilated colon, I'm kind of concerned that they may have toxic megacolon, right? If I see a pneumoperitoneum, I may be concerned that they perforated. But if I don't see a dilated colon, I don't see a pneumoperitoneum, it's highly unlikely that they have toxic megacolon, which is really important, right? So that adds to the utility that it helps to rule out toxic megacolon. If I check again that fecal calprotectin and it's elevated and the ESR and CRP are elevated, it tells me there's definite inflammation of the bowel wall and inflammation in the vicinity of the GIT and it's not IBS. So that helps with this utility here. And then lastly, if I check the stool analysis and the stool culture is negative, the ova and parasites negative, the C. diff assay is negative, it's not infectious diarrhea, and it's likely just a UC flare. All of these things are important to understand, not just the diagnostics here. but also to understand some of the potential complications that we can see in flares and ruling out other differentials such as IBS and infectious diarrhea. All right, we move on to the Mac Daddy here, which is the treatment of Crohn's disease. When a patient comes in and they have Crohn's disease, you have to be able to understand the systematic sequence of movements that you'll go through to treat these patients. So oftentimes you can kind of divide these patients into mild to moderate, maybe moderate to severe and like severe slash refractory Crohn's disease. So we're going to go through each one. In mild to moderate Crohn's disease, oftentimes you can't have it anywhere. And if these patients tend to have their lesions in the colon, they can do what's called mesalamine or sulfasalazine, which is just basically 5-ASA. And what it'll do is it's kind of like aspirin. It'll help to reduce some of the inflammatory processes that are going on in that area. And you can oftentimes give it rectally. If it's ileal disease, meaning that it's the most common location, it's in the ilium, you're not going to do a rectal, you're going to take it orally. And usually this is a steroid like budesonide. That's a very common one that we'll give to patients with mild to moderate Crohn's disease, meaning that they have symptoms like they have right lower quadrant pain, maybe some watery diarrhea. But they don't really have a lot of the extensive complications like of extra intestinal and local complications of their disease, which is very helpful. So I thought we would start here. Mild to moderate, if it's colonic, then induce them. In other words, try to really. put them into remission with 5-ASA. If they get a positive response to that, great. Okay, then I can keep them on the 5-ASA because it's a good maintenance drug and they can take this every single day, usually rectally. There is PO option, but rectally is a little bit easier. Ileal disease, all right, you better induce them with oral budesonide. That'll hopefully put them into remission and shut down this flare-up of CD. If they have a positive response, cool. Then you move on to maintaining these patients on the next step here. which is what's called 6-mercaptopurine or azathioprine. So that's why we're going to move into the next step here, which is moderate to severe Crohn's disease. So if a patient has moderate to severe Crohn's disease, this is a patient who has like right lower quadrant pain, watery diarrhea. Now they're developing some local complications, right? Maybe they're having malabsorption. Maybe they're having weight loss. Maybe they're having some extra intestinal diseases that they're starting to experience. And now I got to escalate the therapy. So the first thing is you need to immediately really abort this flare-up and put them into remission. So oftentimes we'll start off with oral steroids like prednisone. Then later we'll kind of help to maintain them and help them to prevent any recurrence with anti-metabolites such as 6-mercaptopurine or azathioprine. So putting this together, patient comes in, they have moderate to severe, you give them oral prednisone. If they have a positive response, then you're just going to maintain them on azathioprine 6-mercaptopurine. That's usually preferred. Maybe later, as you start moving into the next one, you can consider the initiation of a biologic agent like infliximab, but usually we try to save this until we get into the severe patients. All right. We move into the next step here, a severe refractory Crohn's disease. This is a patient who has right lower quadrant pain, watery diarrhea. They have tons of local complications. Maybe they've had bowel obstruction due to that stricturing. Maybe they've had tons of malabsorptive issues, massive weight loss. They're even experiencing perianal fistulas and abscesses. They have tons of extra intestinal diseases. This patient is really, really bad. We need to try to put them into remission as quickly as we can. If we're going to respond to what we've done to this point, we need to up the anti and go straight to IV steroids like methylprednisolone. Once we've done that, hopefully they improve. Other options is sometimes if you don't want to put them on the right side of the body, you can put them on the left side of the body. on a steroid, you can actually help to put them into remission with infliximab. This is an alternative, especially if they have fistulas. They've been shown that infliximab is usually preferred in those scenarios. Another drug that can be utilized is anti-integrins, vetalizumab. And the last one is interleukin-12 and 23, which is ustekinumab. These work on a couple different pathways and they're usually used as kind of alternative agents instead of infliximab. Or if infliximab fails, you can try these agents. So let's actually kind of put this together. Patient comes in, they have really bad Crohn's. A lot of the local and extra intestinal complications and they're not getting better with a lot of the therapies that we're giving them. You can give them methylprednisolone to help to put them into remission or infliximab to put them into remission. If they have a positive response and they respond, in other words, you put them on methylprednisolone, they go into remission. Great. Then maintain them on infliximab. If you started them with infliximab, you put them into remission, maintain them on infliximab. The other option here is that you can induce them with methylprednisolone or induce them with infliximab. And if you don't want to continue infliximab, you can consider one of these two as an alternative, such as vedalizumab or ustekinumab. But oftentimes, it's usually going to be infliximab. Now, in patients who have some of these complications, medical management may not be enough. And you may have to kind of go a little bit further, and it's important to realize what you need to do. For example, in patients who have fistulas, abscesses, strictures, they may require surgery. And you're only doing this surgery not to cure them of their Crohn's disease, but to treat the underlying complication. You may have to surgically repair the fistulas, cut out the abscess, maybe go in and dilate the open of the stricture, or cut out the affected section of the stricture. So these are important things to remember. The other thing is that patients with Crohn's disease, they do have risk of colorectal cancer. It's not as high as ulcerative colitis, but they do. And because of that, you don't want to miss this. So if you diagnose the patient with Crohn's disease, they should get a colonoscopy every one to three years, eight years after you diagnose them. So once they're diagnosed in eight years, they should get a colonoscopy. And then again, every one to three years after that, to see if you can catch that cancer or any kind of development of cancer relatively early. Quick recap with these is again, I want you to remember that we only induce remission with these agents. 5-ASA, steroids which are the most common one, or anti-TNF agents like infliximab. Maintenance therapies are primarily 5-ASA, so this is an interesting one where you can have both of that. Antimetabolites like 6-mercaptopurine azathioprine. Anti-TNF agents, again it's both an abortive or induction agent and remission agent. And then anti-integrins and anti-interleukin-1223 can also be remission agents as an alternative to anti-TNF agents. All right, that's a lot. So, what are the main reasons for But have no fear, because guess what? We're going into ulcerative colitis, which has a lot of this kind of same concept. So it would be a little bit of a recap. Patient comes in with UC. It's mild to moderate. Maybe they have left lower quadrant pain. Maybe they have some hematocresia, some tenesmus. They don't really have a lot of the intense local complications or extraintestinal diseases, though. All right. Well, then what I can do is I know that most of the time it's local. It's in the rectum and the colon. So oftentimes, rectal 5-ASA, the mesalamine sulfasalazine, is the preferred agent. You can also consider an alternative like multimatrix budesonide, which can be PO or rectal as well. So again, it's one of these two to see if they respond to it. And if they have a positive response, great. You don't want to keep them on a steroid, though. And so oftentimes, we'll either continue them on 5-ASA or we'll move to the next step. which is if they're kind of like not doing really great with 5-A, I can consider upgrading them to 6-mercaptopurine or azathioprine as a maintenance therapy. So let's move in. The patient has ulcerative colitis. They have left lower quadrant pain. They have hematocesia. They have tenesmus. Maybe they're starting to develop some mild extraintestinal manifestations. maybe they had a little bit of issues with colitis and to the point where it's causing so many problems that they're not toxic megacolon yet, but they've had some issues with their colitis and that particular scenario. And they're not responding to what we've just given them. We got to upgrade and we got to go to PO steroids. And that's going to help with induction, but remission will be required with the anti metabolites. So give them prednisone, help to get them in remission. If they have a positive response, they're in remission, maintain that with 6-mercaptopurine or azathioprine. This is more preferred, but you can consider infliximab, especially if they're having somewhat of a poor response to this. Let's move into the next one. We go into severe refractory ulcerative colitis, left lower quadrant pain, hematochesia. They also have again the tenesmus. They're having extra intestinal manifestations. And on top of that, they've even had maybe some episodes of toxic megacolon. Maybe they've perfed a bowel. These maybe even they've had other issues. And now because of this, I'm concerned that they are in severe refractory UC. In this particular scenario, we have to shut this down. We have to induce these patients to go into remission with IV steroids. Another alternative is infliximab though. And then we have to maintain these patients on infliximab or an alternative like anti-antagrins like vedalizumab. Let's put it together. They come in, they get induced with methylprednisolone or infliximab, one of the two, it doesn't really matter. But they have to be maintained not on methylprednisolone if they respond positively. They have to be maintained on infliximab or vedalizumab. And usually it's infliximab that's the preferred agent. If they do have complications which can arise, lies. We can do the best we can to medically manage them, but sometimes it may require surgical management. Here's the interesting concept. If a patient has toxic megacolon, they have colorectal cancer, or they perf, we can actually do a hemicolectomy. We can remove the disease segment. We can remove the cancer segment, and believe it or not, it's completely curative. You remove the area that's affected. They require a colostomy bag, but at least they will have no further incidences of ulcerative colitis. That is a big difference between that and Crohn's disease. The other thing that's important is that these have very high risk of colorectal cancer. Because of that, when they are diagnosed with UC, eight years after the diagnosis, they need to get a colonoscopy in every one to three years or more sooner or more frequent, depending upon what they find in the actual colonoscopy, because you want to catch that colorectal cancer early before it's too late. And again, these are the induction agents, 5-ASA, steroids, anti-TNF. Maintain. with 5-ASA, anti-metabolites, anti-TNF, anti-integrins, and anti-endolucan-1223. That was a lot, right? Well, guys, we got through it. We pushed through inflammatory bowel disease, and I hope it made sense. I hope that you guys enjoyed it and learned a lot. And as always, until next time.