Approach to Diarrhea

Welcome back to Run the List, a medical education podcast and partnership with McGraw-Hell Medical. Our host are Dr. Naveen Kamar, Dr. Walker Red, Dr. Emily Gatowski, Dr. Joyce Ow and myself Blake Smith. As a quick disclaimer, this podcast is meant for informational and educational purposes only and should not be understood as medical advice under any circumstances. Welcome back to another episode of Run the List. In the last couple of episodes in our Gashar in Aurology series, we've been covering upper GI bleeds, lower GI bleeds and biliary track stones, but today we're going to turn towards a different topic, diarrhea and how to approach thinking about it. But first, I'll introduce the one, the only, Dr. Naveen Kamar, Run the List founder and attending gastroenterologist at Brigham & Women's Hospital, associate medicine clerkship director at the Brigham and also Harvard Medical School. So without further ado, Naveen, are you ready to run the list? Absolutely. I hope our listeners aren't getting bored of my voice. I've been here for quite a bit, but it's exciting to do this with you Blake. Thanks for having me again. Of course. We're the expert GI attending here, so we're thankful to have you for the series. So I'll begin by introducing the case of a 42-year-old female who presented to the emergency department with a three-month history of progressive diarrhea and worsening abdominal pain. She's been otherwise healthy with no significant past medical history and previously normal bowel movements, but is presenting with weight loss, fatigue, and again, three months of progressive bloody diarrhea that is preceded by crampy abdominal pain. Her vital signs are, she's slightly tachyocardic at 105. Her blood pressure is 115 over 78. She's sat in 99% on room air and has a respiratory rate of 16. She has no significant medication changes and is not currently taking antibiotics, but the patient mentioned that she also had no significant dietary changes nor any recent travel history. There are no notes in the EMR, and she's previously never had any hospitalizations before, especially not for diarrhea. On exam, the emergency medicine resident noted that the patient's afebrile should some tenderness to palpation in the lower abdomen, and she appear to dry an exam with dry mucosa and some skin paler. Labs were notable for an elevated CRP of 85, ESR of 18, and a reduced hemoglobin of 12 and hematocrit of 37. Her CBC showed mild leukocyteosis of 11,000, but with a normal differential. And the remainder of her labs are normal. So Navi, that was a lot, but can you start by mentioning how you think about a common presentation such as diarrhea? Absolutely. And you're right. It was a lot, but I do appreciate having all that information because the differential diagnosis for diarrhea is quite broad, and you really need to spend a lot of time, particularly in the history taking phase, to really kind of begin the process of making a diagnosis. So thank you for all that information. And then I just want to take a quick step back and make sure we know what we're talking about. So I think with diarrhea, the first key thing is to ask yourself, is this truly diarrhea? So the definition of diarrhea is the presence of loose stools. Like you may get a kick out of this, but there's actually a stool chart that's quite commonly used in gastroenterology and also in internal medicines called the Bristol stool type. Are you seeing it before? I have, and, you know, believe it or not, friends of mine have even sent me the stool chart. Friends not in the medical field who've gone on recent trips to Mexico and elsewhere and have asked about it. So yeah. It's awesome. It's making the rounds. Yes, that's awesome. So, um, well, I mean, a lot of reasons I went into GI's because it kind of fit my personality and I do find it sometimes talking about stool, especially for some people who can get uncomfortable. It's a little funny, but in any case, this Bristol stool type chart can actually help you give an objective, uh, health patients, give an objective description of what type of stool, um, they're experiencing. So the Bristol stool chart, it moves, it has seven types, uh, one through seven. Four is generally right in the middle, kind of the most normal stool. And then one through three are the harder, more constipated type of stool you'll see. And then the, uh, stool types five through seven, which you see in, uh, cases of diarrhea. So you want to first confirm that the types of stool that the patient's having is actually lose stool, which would be Bristol stool type five through seven. And then you want to confirm the presence of increased frequency. So normal bowel movement frequency is anywhere from one to three bowel movements a day. It's kind of surprising. I know I have a lot of patients who's too tell me that they're having three bowel movements a day and that, to them that feels like diarrhea, but it's actually by definitions when it's over three, um, stools per day that constitutes diarrhea. So the first thing I do is I make sure is this patient truly having diarrhea, certainly not in, in this case, um, this patient is at that point. I know we didn't have the specifics about the, the frequency, but um, Blake, can you remind me how many times was she going per day when you asked her in the emergency room? She was mentioning anywhere between five and 10 times a day. All right. Perfect. So yes. So now now that we've confirmed that she's having clinical level of diarrhea, the next step is to think about how long have these symptoms been present because there's a, there's a key difference between patients presenting with acute diarrhea and those presenting with chronic diarrhea in terms of when you think about the differential diagnosis. So acute diarrhea falls in the timeline of less than four weeks. And the vast majority of acute diarrhea presentations are due to infection. So the differential is much more narrow, um, in that case. Now compare that to chronic presentations of diarrhea, which are defined as, as symptoms lasting for four or more weeks, the differential is a lot more broad. And although infections are much less likely, you still have to think about parasitic infections based on their risk factors. You mentioned that this, that this patient didn't have any recent travel, um, to an endemic area. So infection is much lower on the list and as we'll get to in a second, uh, the categories for potential causes of chronic diarrhea are much more broad. So after you've defined the presence of diarrhea and you've nailed down the timeline, uh, again, in this patient, she does meet criteria for diarrhea. And in terms of timeline, we're thinking about chronic diarrhea. I then like to apply a framework, a diagnostic framework to help me organize my thinking. Uh, as I'm building a differential diagnosis. So the framework I like to use, there's a lot out there, but I like the three category framework of watery versus fatty versus inflammatory, uh, causes of diarrhea. And the reason I like it is because in your conversation, in your HPI with the patient, their description of their stool is going to lead you into one of these three categories. So you really are utilizing the history to start framing your diagnostic, uh, workout. So let's go through each of those three big buckets. So, uh, in watery diarrhea, there's two main categories that you think of. The first category is osmotic. So this is, this suggests that there's something that's in the intestinal system that is not getting absorbed and is producing an osmotic gradient that's bringing water into the intestine, leading to increased watery output. And so the most common, uh, cause of osmotic diarrhea that we think of is lactose intolerance. The simple fact that patients with lactose intolerance are not able to break down the lactose and absorb it, it becomes a relevant osmotic feature within the lumen that's bringing water and causing diarrhea. The other common one is laxative use. I mean, a lot of our laxatives that we use, especially those over the counter, merilax, milk, amagnetia, magnesium citrate, they're all rely on producing an osmotic gradient sending water into the colon. So sometimes you, they do have these situations where, where surptitious laxative use or, or, or also just patients who don't know what they're taking and, um, surprisingly, it's, uh, they're actually on laxatives that's producing diarrhea and they just weren't aware that that was, what was going on. Okay, so, um, the key thing with osmotic causes of diarrhea, the key question is to ask does it get better with fasting? Because if you're not creating that osmotic gradient, uh, by whatever you're ingesting, the diarrhea will resolve. So, like, do you have a sense of, like, the best question to ask about that to determine when you're talking to a patient? I would imagine maybe changes in, in dietary intake or even if they've fasted recently and see any, any improvements. Exactly. I definitely, I just put you in a spot, but you're absolutely right. And then naturally, what you can also ask is what happens when you go to bed, right? Because everyone, for the most part, fast overnight. And so the key question is, do the bowel movements persist overnight versus do they resolve? Um, and so if they do persist, then you're into the second category amongst the watery diarrhea causes, and that's secretory diarrhea. And so in addition to the fact that these, the, the causes of secretory diarrhea, those presentations will continue throughout the day, regardless of PO intake. They also tend to be large volume stools as opposed to osmotic diarrhea, which is a smaller volume but frequent stool. So with these large volume stools, there are some very rare causes hormonally based that you can think of this, the Zollinger Ellison syndrome, due to hypergastronemia. There are VIP omas. There are carcinoid syndromes. These are all very rare, uh, but there's also some more common causes of secretory diarrhea. And that includes post-colostestectomy phases where the patient is actually dumping bile into the small intestine. The small intestine is not able to absorb, reabsorb the majority of that bile salt. And once that gets the colon, that actually stimulates the colon to cause a secretory diarrhea. And so we can call that post-colostestectomy syndrome is also another entity that we just that includes post-colostestectomy state, which is bile salt diarrhea. And as various causes of bile salt diarrhea, you can imagine any, if the bile salt is going to absorb it in the small intestine, primarily the terminal ilium, if there's any disease state in the terminal ilium, or if you've had a terminal ili resection, you're going to have more bile salt spilling into the large intestine, producing this secretory diarrhea. So I think about osmotic and secretory. And then in addition to those two big categories, I have this other category, I think of this other. And within that other category, it's probably the most common cause of chronic diarrhea, which is a functional or urinal bowel syndrome diagnosis. But then also think about things like hyperthyroidism that are going to stimulate motility, obviously with hyperthyroidism, you're sending off a TSH and you'll see evidence of other manifestations of elevated thyroid within that patient's presentation. So that is watery diarrhea. Let's move on to the next category of cause of diarrhea. For that, I want to bring up fatty, which basically the patient will report features of fat in their stool. Now sometimes they'll say their stools are oily or greasy. Other times they'll say their stool is floating to be honest, floating stool is not uncommon because all that means is that there's some air trapped within the stool, right? So a lot of patients may bring this up, but the key question I like to ask is it oily, greasy, and is it difficult to flush? Because that all suggests that there's some oil component from malabsorption that's driving their diarrhea. These patients may also have some non-specific symptoms such as bloating or flatulence, but those symptoms won't clinch the fact that they're having actual fat malabsorption. I think really trying to tease out are they having true staturia as the key question. So within that bucket of fatty diarrhea causes, you have things, think about things that cause malabsorption. So celiac disease should definitely be high in a differential there. And for that, I send celiac serologies. For the initial workup of celiac, I always start with non-invasive evaluation with serologies like just mentioned. So that's setting a tissue transglutaminase. Now the tissue transglutaminase, you can, the best screening test is an IgA, form of that antibody. So when you send the TTG that's IgA-based, you also have to send a total IgA level. I feel like that's a second level move that I learned during fellowship because if the total IgA is low, which is actually not that uncommon, right? You could potentially miss underlying celiac disease. And if their total Ig is level is low, there's other serologies that you can send to investigate that diagnosis. Now in addition to celiac, another entity is becoming quite common. I think we're just, we have a better knowledge of this condition is SIBO or small intestinal bacterial overgrowth. And then Blake, do you know how we diagnose SIBO? Yeah, I think I remember a breath test and some other clues to malabsorption in small intestine. Awesome. Yeah. So the breath test, it's a lactuals breath test where you actually give the patient lactuals and then it takes a little bit of time. It's usually about a two to two and a half hour test where the patient of every 15 to 30 minutes blows into a bag. And then we measure the gas levels, ideally hydrogen and methane as there's two different forms of SIBO that patients may have based on that gas composition. And then if the gas levels reach a certain threshold, we consider that diagnostic of having underlying SIBO or a small intestinal bacterial overgrowth. And you brought up a really good point about how sometimes you see evidence of SIBO on regular routine labs. And so what Blake is referring to is that you can see B12 deficiency in patients who have very advanced SIBO because the bacteria that have overgrown in the small intestine are actually competing and using up to B12 that that patient is ingesting. And then interestingly enough, the folate actually becomes very high and usually above acid because the bacteria are actually generating folate. And so if you have a patient who you happen to have some anemia labs and you see a low B12 and a folate of acid, that's pretty suspicious for them having underlying SIBO. If they also have the accompanying malabsorbative symptoms. So we talked about celiac SIBO under this fatty umbrella of causes of diarrhea. I'd also want to add in pancreatic insufficiency, which like I don't know if you, I have a lot of patients who are coming asking for this testing. I think it's getting a lot of marketing attention in the general population. And so I mean, I have to say exocrine pancreatic insufficiency is fairly rare. You have to lose over 90% of your pancreatic function for this to occur. So most of these patients have had recurrent amounts of pancreatic or very severe episodes of pancreatitis to get to this state. But if you do have some prior history of pancreatic disease and you have the patient also endorses some malabsorbative symptoms, you can send a fecal alastase. The key thing with the fecal alastase is that it needs to be sent on a form to stool specimen because it's a concentration. And so if you end up submitting a loose bowel moment, a very watery stool, it's going to dilute out the fecal alastase and that will make it look like the patient has underlying exocrine pancreatic insufficiency. All right. So I'm giving a lot here, but let's keep going. We're going to finish up the final bucket. We've done watery, we've done fatty, now let's do inflammatory. And so amongst the underneath the inflammatory bucket, we principally are thinking of patients with inflammatory bowel disease. And the quality of the stool in inflammatory diarrhea is usually bloody as it is in this patient. But then they also may have signs of inflammation in other parts of their body. They often have abdominal pain that's accompanying their presentation with diarrhea. And again, we're thinking mainly here of Crohn's disease versus ulcerative colitis. I do want to mention microscopic clasps because it is a common cause of chronic diarrhea. Although microscopic colitis, despite it causing inflammation in the colon, it does not produce an inflammatory stool is generally a watery stool, a watery painless stool. Don't forget about microscopic colitis when you're using this framework, but just remember that it doesn't actually fit the characteristic inflammatory stool. Naveen, that was awesome. I'm going to let you catch your breath and I'll do a quick recap for the listeners because you offered so many helpful pearls in your framework. So Naveen's framework is kind of a three pronged approach of watery versus fatty versus inflammatory diarrhea. But his first step in general, given that diarrhea, is a common presentation and patients are kind of aware of their own bowel movements. But main question is, is this diarrhea? And so Naveen characterize it as loose stools with increased frequency above three stools daily and also to think about it in terms of duration in acute versus chronic where chronic is greater than four weeks of diarrhea. The framework that Naveen applied is watery diarrhea, which within it has osmotic, secretory, and other fatty diarrhea, which you know, stiateria is kind of the classic feature seen in celiac, but also SIBO and pancreatic insufficiency, and then lastly inflammatory diarrhea, which is marked usually by bloody content in the stool. And it's main examples are inflammatory bowel disease. This patient in our case today did note bloody diarrhea that was progressive for three months. So greater than that four week time span and noted crampi abdominal pain with each bowel movement. And so Naveen, I hope you got a drink of water, a breath of air, because I have another question for you. As you know, we're further evaluating this patient, what else do you prioritize in history taking in addition to stool quality, duration, and timeline? Yeah, let's do it. And thank you for that summary, because I think with diarrhea, you have to keep going over this quite a few times where it to become second nature. So after you've applied the initial framework, the next thing I think about is my patient experiencing any alarm symptoms. Because if they are, that will help narrow my differential, and also give me a sense of urgency in terms of the work up. This is if any of these alarm features are present, I want to figure out what's going on in a sooner basis, and also I would say I'm much more apt to do something invasive to find out what's the underlying cause. So let's go over our alarm features. So the alarm features include an age of onset over 50 years old. So this is, it should be, it's alarming when a patient who's had normal bowel winds for the majority of their life, all of a sudden start having a change in their symptoms. Other, the next alarm feature is any evidence of GI bleeding, so are they having bright red blood, are they having maroon stool or melanin, and going along with that, we can go to the next alarm symptom, which hinges on lab findings. So do they have iron deficiency anemia that suggests chronic ocult or overt GI bleeding, as well as labs that signify elevated inflammation. So elevates CRP, ESR, and then we'll talk about the fecal calp protect in a little bit that's a very helpful stool test for inflammation. I also ask about constitutional symptoms, so are they experiencing weight loss, fever, night sweats, any of these things would raise alarm. And just to take a brief step aside, when we're talking about alarm features, we're really concerned like do they have significant inflammation or malignancy that's causing their symptoms. So when you hear weight loss, you obviously think about could they be having malignancy, but it's also could be a sign of inflammatory bowel disease as well. We talked about nocturnal symptoms before in terms of cause of secretory diarrhea. It's also relevant here because a lot of times patients who have inflammatory bowel disease, and this is where it gets a little confusing, but if you have significant inflammation, you can also produce a secretory diarrhea as well. So ask about their symptoms persisting overnight, and then certainly do they have any family history of inflammatory bowel disease or colorectal cancer. So looking back at our case, as you already nicely summarized, she has, she does meet criteria for diarrhea, timeline is chronic, and then her presentation with, you mentioned how the progressive diarrhea actually was was bloody on further history. So now the fact that she has blood in the stool suggests that all those three categories watery fatty or inflammatory, she fits in the inflammatory bucket. And now we're seeing when we go back and look at the labs that she gave, she actually has alarm features of a mild anemia to confirm that this is iron deficiency. I'd say iron studies as well and get a serum iron and a total iron binding capacity so I can calculate a transfer in saturation and a serum ferritin also, although that may be falsely elevated, sorry not falsely elevated, but it may be elevated in the setting of inflammation. And then also you gave the elevated inflammatory markers of CRP and ESR. So taking it all together inflammatory bowel disease is quite high my differential at this point. Thanks for walking us through that initial diagnostic framework and talking about alarm features and when to need to escalate your investigation of the patient's diarrhea. So now that we're arriving at this diagnosis of inflammatory bowel disease or IBD, what additional workup would you send at this point? Yeah, so here's when I start thinking about what can I do non-invasively? I know this patient's presenting the emergency room, but oftentimes these patients present in clinic and so you have to think, what can I do now and what do I need to schedule for later? Usually when I'm thinking about scheduling, I'm thinking about some invasive testing. So within the non-invasive bucket, I'm thinking that it's still important that we rule out infection. Again, this is less likely because this is a chronic diarrhea, but I would certainly send a CDIF, both because it could present chronically if it hasn't been diagnosed earlier, but also there's a higher risk of CDIF in patients with inflammatory bowel disease and sometimes the CDIF can actually be what causes the flare of the symptoms that leads to the presentation. So I definitely send a CDIF, and then I'd also consider sending bacterial stool cultures or parasitic testing with an O and P and G-arty antigen. If they have any risk factors such as recent travel and notably usually these patients present in the acute phase and may see their outpatient doctor, I'm not sure if that was a case for this patient, but if back to your stool cultures, parasitic testing were never tested during this phase of diarrhea, I would certainly think about sending that as well. And then when I mentioned earlier, the fecal cowl protectant is a really, really helpful test. It measures for inflammation in the intestine. And in this case, I think it would be very helpful to get morph, so to obtain a baseline level of inflammation, you can track the fecal cowl protectant. We're thinking this patient likely has inflammatory bowel disease. So fecal cowl protectant will be something that will be helpful to follow over time. And the reason why it's more relevant for in this case as a baseline is that we are going to proceed with a colonoscopy. Sometimes you use the cowl protectant to decide whether or not a colonoscopy is needed. In this case, we definitely need to do one because she has those alarm features of anemia and blood in the stool and elevated inflammatory markers already. So that leads us to our next bucket of workups and that's invasive strategy here. And so she needs to have a colonoscopy. And I make sure that she gets biopsies throughout her colon as well as the terminal Ilium because that's going to help us differentiate is she having ulcerative colitis versus Crohn's disease. And we'll talk more about this in our next episode, but just briefly to kind of differentiate those two diagnoses. Remember, UC starts in the rectum and then it moves proximally in a continuous pattern and it's circumferential. So it's generally is involving the entire colon as you're moving up to a certain point. Do you? Some patients just have left side UCs and it's really interesting on colonoscopy. You'll see a clear demarcation between where the inflammation is and where the normal tissue is. It's really, really cool and it's typically to see that. But some patients have that inflammation extend all the way through their large intestine. Occasionally, you'll actually see evidence of Iliitis in a patient with UC and we call that backwash Iliitis. That typically is seen when the patients have the inflammation extending all the way to the right side of their colon. And then compare that to the Crohn's disease presentation where the inflammation can be found anywhere in the GI tract. Sometimes they have upper GI involvement. Sometimes it's lower. Sometimes it's small intestinal. Often the terminal Ilium is involved. And I do want to say make another exception here with the general rules, right? So we talk about how UC is in general an inflammation that extends proximally and continuously. Occasionally, you may just see a patch of inflammation around the appendiceal orifice in patients with UC. And that's called a sequel patch. And that is a diagnosis sign of ulcerative colitis. So there are some exceptions to these rules of where the where the inflammation is present, how continuous it is on both sides of the equation. But it is important to kind of remember the general features to help differentiate the two. A lot of this differentiating while you're actually doing the procedure based on what you're seeing. And thanks for providing kind of those classic signs of IBD within which is ulcerative colitis or UC and Crohn's. So let me provide some updates based on this additional workup that Naveen described. The patient's seeded testing returned negative. She mentioned in the beginning that she had no travel history and her infectious stool studies for OMP and GRDR sent by her PCP earlier in her course were also negative. The fecal calprotectin is sent but is pending. And so based on the alarm features and this chronic diarrhea, Naveen performs colonoscopy, the invasive strategy on this patient. And noted erythema starting in the rectum and progressing proximally throughout the colon in a continuous and circumferential pattern. Naveen noticed that there is loss of ascularity in the colon wall as well as friability but no deep ulcerations and the terminal ilium is normal in appearance. He obtained biopsies throughout the colon and in the terminal ilium to confirm but those results are also pending. So what do you expect to see on histology based on the endoscopic findings that you saw? Yeah and so the colonoscopy findings that I found and that you summarize nicely. Note that, so this is consistent with UC, right? Because you're mentioning that we're seeing erythema, loss of ascularity. These are all classic endoscopic features of inflammation in the bowel and the fact that it starts in the rectum. It's extending proximality in a continuous fashion throughout the entire colon. This fits with diagnosis of PAN UC with PAN colitis, especially the part of that there's no TI involvement. So expecting this to look like UC, first of all, you do want to see evidence of chronic active inflammation on the pathology reports and there's various clues into this diagnosis that our pathologists use but I think one specific pathologic feature of UC is a presence of crypt abscesses. And so the pathologists are looking for that type of feature histologically when presented with a case such as this patient but in general, I think just purely based on the endoscopic appearance, this really does look like UC. And then the key piece is making sure there's evidence of chronic active inflammation when there's just active inflammation. You don't have enough features to actually say this is inflammatory embodies because that's a chronic, right? And this is like, that's a chronic diagnosis, so you want to see evidence of chronic active inflammation. Yeah, that's great. So let's pause here as we definitely have covered a lot of material in this episode and Naveen has given us a ton of information on how to diagnose diarrhea in general and how to approach it and more specifically now how to classify inflammatory bowel disease on endoscopy and also on histology. In this patient, the 42-year-old female, we've arrived at a diagnosis of ulcerative colitis, involving the rectum, but sparing the terminal alien, a pan colitis picture, as Naveen mentioned, her histology report came back showing chronic active inflammation with cryptopsysies confirming the diagnosis. So we'll pick up from here in our next episode where we're going to really focus in on inflammatory bowel disease management. But before you go, can you leave us with a few last pearls? Absolutely. Thank you, Blake. Yeah. So, pearl number one is to remember your definitions, really nail down if your patient's actually presenting with diarrhea. And if so, then move on to the second phase of characterizing the diarrhea as acute versus chronic because as you do this, you'll be able to start building your differential diagnosis. Second pearl is use a framework of which there are many, but I like the watery versus inflammatory, versus fatty framework. And one thing I actually didn't mention earlier was medication usage as many medications that cause diarrhea. I mean, typically when medications cause diarrhea, they happen on the earlier side of things, so you probably catch this in the acute phase. But some patients may be on medications for long term, and by the time they present, they're in that chronic phase. So don't forget about checking the medication list for any potential co-factors there. And then a third pearl I want to leave you all with is to use alarm features that list of various signs or symptoms that are alarming that raise your suspicion for the patient having a more serious diagnosis such as inflammatory bowel disease or malignancy. Because as those, if any of those alarm features are present, not only is it going to help you narrow your differential, but it's also going to help you decide on how urgently do you need to work out with the patient and with what tools, definitely favoring an invasive evaluation with colonoscopy and biopsy if those are present. Awesome. Thank you, Naveen. We hope you enjoyed this episode, and we'll join us again on another episode of Run the List. And in our next episode, as I mentioned earlier, we're really going to focus in on IBD management. So we'll see you then.