Episode 408 – Clinical Unknown Series with Dr. Kirtan Patolia

Welcome back, clinical problem solvers. Maddie and Yusuf here. At CP Solvers, our mission is to make clinical reasoning accessible to learners worldwide. We invite you to join us for our live virtual morning reports, where we break down cases and sharpen our diagnostic reasoning together. Now over to you, Youssef.

Thanks, Maddy. Just a quick reminder, this podcast is for educational purposes only and is not a substitute for medical advice. Patient details have been modified to protect their privacy and the views expressed through our own, not those of our employers. Now, let's dive into the case. Enjoy the show. Hello, everyone. Welcome to another episode of the Clinic Call No series.

My name is Debra. I'm a Brazilian, graduate on Argentina, and I am currently living in North Carolina, studying to apply for residency. And I'm here with my dear friend Noah. Hey everyone, I'm Noah, a Brazilian physician and now internal medicine resident in the States. And we also have Mark here. Hey everyone, my name is Mark. I'm from New Jersey and I did my medical training in Philadelphia and I'm currently a second year hospitalist at Stanford.

The Clinical Unknown Podcast is a series that have us three as leaders, and in the podcast we present a medical case in aliquots to a guest that has no details about the case. The guest goes sharing...

their thoughts and insights. Our brilliant guests are part of our team. Besides the podcast, we also have a website with diagnostic schemas and illness scripts. And we also host daily free zoom-based morning reports where guests present clinical knowns to our team live much like our podcast the links go out on a mailing list found on our website

And we also have the Clinical Problem Solvers Academy, who is a group run by medical students, residents, fellows, and attendants, whose mission is to disseminate and democratize the teaching of clinical reasoning. We are a nerdy but fun group.

who would love to talk about medicine, clinical reasoning, medical education, life, and all things in between. We invite people that are active in our virtual morning reports to join the CP Solvers Academy and learn together. Visit our website to learn more.

Hello everyone, welcome to another episode of our Clinica Know series. Today we are going to present another fantastic episode with a great discussion and I'm the pleasure to be here with... Noah and Mark. Mark, do you want to say hello? Hello, hello, everyone. My name is Mark again. I'm one of the CP Solvers Academy members.

First year, but secondly, now second year hospitals at Stanford, which is crazy. The year is flying by. And I can't wait to discuss with our wonderful CP Solvers Academy member. I will let Noah introduce him. Hey, everyone. I'm Noah. I'm a Jar now, not a Nintendo anymore, a WashU. I think Jar is so funny. Look aside, it always reminds me of Jar Jar Blinks from Star Wars. And I'm super excited to have you here.

discussing the case. My dear friend, Curtin, who will be joining us very soon. Curtin, do you want to say hello? Thank you so much for inviting me to this podcast. Like I have been waiting to come here and learn from you guys. And always when I'm in the gym and I'm listening to you guys, the initial five minutes, you always do so much fun. And I'm jealous that.

In our podcast, we never got a chance to do such kind of fun. So finally, I'm excited that I'm here. And also on the serious note now, Noah is going to become PGY2. And already I have heard so many good stories. about Noah's PGY1 from Marcela that how he's so smart so talented but also mischievous so I want to see how he handles the stuff when he becomes PGY2 and I would be

grateful that I would be at the WashU with Noah to see how he is doing and we will have fun learning together and also excited to be with Mark. It's always fun discussing with Mark that takes off the pressure of me so I think it would be great. And again, thanks to Deborah as well for inviting me. And how are things going with you Deborah? All good?

Yeah, it's going great. We are super happy to have you here today. And I always think that is so funny. I know when Marcela has a group chat with you, when they have doubts, they send to you. You are almost like their chat. I think it will be a great journey for you and at WashU. We are really happy for you. And trying to do an icebreaker, I want to know.

For you guys, which superpower you guys would want to have it? I think I would probably want to be invisible, you know, sometimes disappear a little bit. Be on my own. Sometimes hear some conversations from other people to see if they are talking about me. And yeah, let me start with you. Kirchan, what would be your superpower? Perfect. This is the favorite part of my podcast. This fun stuff. So I would like to mention.

two superpowers one the serious one and one the funny one so the funny one i would say so during my recent interviews i always used to say that when people will ask me that what's your story like tell me about yourself and the first thing i will say is

that you know what I am from state of Gujarat the western part of India and we love to eat lots of sweets and that's why we are sweet people you know and then everybody would be like oh you know things like that so my superpower would be that if I can eat sweets all day long and not get diabetes not get any kind of cardiovascular disease if that happens oh my god it would be so good and the second superpower would be they're like this is more like serious one you know they're like

we love the signaling pathways we love the molecular pathways but i always used to wonder when i was a kid that like how did scientists ever figure out that okay this molecule is like ras or something this molecule is like G protein copper receptor like how do they attack it and how do they visualize it so like if there was super power that I could be small enough

I could go inside the cell and I could literally see all these pathways, you know, like playing along, interacting with themselves. That would be so fascinating. So yeah, those will be the two powers I would like. I love it. I think everyone wants to eat sweets and don't have any diverse effect. Noah, what would be your superpower? I think I'm also going to have two superpowers, but there are two kind of...

silly superpowers one i just wish my day would have 48 hours instead of 24. so like i'm constantly running behind and there's like so many things i want to do I just started senioring on medicine and I want to get home and I want to rest, but I also want to read about medicine and dig deep into my patient's chart and really think about what's going on. So that's my first superpower.

And the second superpower is I wish I didn't feel temperature. I was impervious to temperature. Here right now in St. Louis, we have such a bad heat wave. That's like you go outside for 10 minutes and you're like actually feeling ill. And thinking about it, you know, imagine how nice would it be for you to just go on winter wearing normal clothes and not have to, you know, do the whole put your jacket on, put your jacket off or go out in summer.

on those days and just be able to run around so those are two very silly superpowers but i think that my life quality would increase so much what about you mark Well, no, I definitely want to hear more about this mischievous activity that Kirtan is referring to, but maybe we will talk offline about that.

I think the superpower that I always think about is flying. I just like love to travel. And I feel like if I was able to fly and kind of see that bird's-eye view of the world, it would be awesome. And like, you know, like... who wouldn't want to like fly to like japan after a day of work right so i think it would be a good way to you know come down from a week of work so yeah i would love i would love to fly

Amazing. I love it. All the answers. Noah, do you want to start off with our case? Sure. It's going to be a great case and I'm super excited to see what you're going to make out of it. So we began by hearing about a 61-year-old bell that comes to the emergency department with two hours of Russian chest pain. He also is complaining of a cough and a fever. for a week or so. And I'm going to stop here. Marcos, I think we have an interesting chief complaint. Which one would you focus?

on this case. Yeah, no, this is a, this is a great chief complaint. I mean, this is something that we see day in and day out in the hospital. You know, me as a hospital, seeing an elderly patient with acute. chest pain, fever, and cough. It's just, it's one of the most common, I think, syndromes that comes into the emergency department. So I think the first thing I'll just talk about is the chest pain, right? Because I think

you know, that's really the most deadly symptom that the patient has. And, you know, we have a great mnemonic in the CP solvers, the four plus two plus two mnemonic of like the no missed causes of chest pain. So, you know, you think about things like acute coronary syndrome. For the cardiac causes, aortic dissection, takotsubos, a pericardial effusion slash tamponade. For the pulmonary causes, you can think about a pulmonary embolism and a pneumothorax.

And then for the esophageal causes, you can think about esophageal rupture and impaction. But then kind of think about, you know, of those cardiac causes, you know, which of those cardiac causes can cause inflammation or fever, right? Um, it kind of rule, it kind of narrows down that list a little bit, right? Like for instance, acute coronary syndrome.

And doesn't tend to cause fever. Now you can maybe think of unique causes of acute coronary syndrome, say a patient that has endocarditis with a coronary artery embolism. Now that can cause, you know, fever and chest pain. But again, extremely, extremely rare. You know, you can think about someone with pericarditis that has tamponade and has chest pain. And the many causes of pericarditis, you know, can also has fever. It's commonly cited that a pulmonary embolism.

is a cause of fever. I would say I see a lot of patients with pulmonary embolisms and blood clots. I haven't seen too many cases present with fever, but it is on the list. So it is a consideration. But I would say within the four plus two plus two mnemonic, you know. I mentioned the acute coronary or vascular causes that could cause this fever, the pericardial causes. But Kirtan, I'm curious how you would kind of layer in maybe the cough as well and how that would influence your differential.

Perfect. Thank you so much, Mark, for laying down the framework for me. And I agree with you that whenever we are dealing with three or four complaints and all of them are relatively common, it's better to tackle the one which is life threatening and you don't want to wait for it.

you can figure out along the way and often it can also happen that maybe one of these complaints was not relevant at all like it didn't pan out the way we wanted it to be and also the fewer part is kind of interesting that This patient has chest pain for two hours, but how would somebody feel that they started having fever two hours ago, right? It's kind of unusual that...

Almost always it is possible that maybe patient was feeling a little bit malaise, little bit fatigue, maybe like kind of feverish at home. And now you are documenting the temperature. which is like let's say about 38 degrees in the ER and you think that patient has fever. So I think again clarifying the history a lot more will be helpful to see that when did the fever start. And I agree with you that the cough part that how it can overlap. with this crushing chest pain.

ACS usually would not cause it but let's say if somebody has pericarditis then I have many times seen that the posterior part of pericardium often touches the bronchi and it could touch the left bronchi depending on the anatomy that's why often pericarditis is cited as one of the kind of cryptic causes of cough, hiccups, and so many different things related to the airways. So that is when we were thinking about it, that if this person really had, let's say,

classic acute onset viral myopericarditis then it could end up causing crushing chest pain, some degree of fever and also cough. So that is great. The other possibility is that although Noah has told us that the chest pain is crushing.

It might be perceived differently by the patient so it is also possible that maybe the chest pain was let's say stabbing in nature then suddenly pleuropericarditis would be high on our differentials and so many entities which can cause pleuropericarditis or serocitis including acute pneumonia or viral infection. can end up causing fevers and cough as well. So I think moving ahead, what we can do, we can get the history a lot better. We can at least get the EKG, we can get the troponin.

And as Mark was saying that we have to rule out all those other etiologies of must not miss of causes of chest pain. So we will get the city chest as well. And then we will move ahead. That's a great discussion. And I really like how you mentioned that the crushing nature of the chest pain is not really specific nor assistive ACS. So giving a little bit of more information.

um those patients when they go to the ed we always have their vitals right so uh his bp was 110 over 70 his pulse was around 110 his respiratory rate was actually 32. His temperature was 101, and he was starting 88% on room air, which slowly increased to 93% on 5 liters. When you talk to him, he tells you that he's been feeling kind of...

ill for the past week or so with subjective episodes of fever at home. He's been coughing quite a bit and he's actually been having some bloody expectoration seen in the AED. So you actually see the bloody streaks in his sputum. And then this morning, he started having this episode of chest pain, but once talking more to him, he describes it as more of chest tightness associated with increasing feeling of shortness of breath.

he was really unable to do all his activities and that's why he came in physically exempt for him was kind of unremarkable he had some full of systolic murmurs, had some crackles and bilateral bases, no lurchion and edema, nothing else remarkable in the physical exam. So you take a break, you know, go try to review him a little bit, look at his past medical history.

not really much he has hypertension mitral valve prolapse status post by prosthetic valve in 2016 and he had a few episodes of perxismo afib which is not on any attack population. As far as MADS, you're just on Bazinopril for the hypertension and it's considered to be well controlled. Kyrton, what does information add to your thoughts now?

perfect thank you so much noah for giving the additional piece of information so just so as to make sure that i don't miss anything i would like to summarize it so we are dealing with a 61 year old gentleman who is presenting with almost one week of generalized fatigue, some fever and malaise. And along the same time, the patient has also been experiencing intermittent hemoptysis.

and over last couple of days the patient also started having cough dyspnea which was limiting the exercise abilities and now the patient also has chest pain for last two hours and now we are seeing him. So this helps us in getting a good picture of what's going on that things didn't start two hours ago things actually started like one week ago and this has been brewing slowly what is relevant in past medical history is that this gentleman has bioprostatic valve and

patient has AFib, not on any relevant medication. So when I think of hemoptysis, I always ask myself that is it life-threading hemoptysis or not? because that can guide us that whether this patient belongs to ICU or this patient belongs to general medicine floors. On our CB solvers website, there is a wonderful EMOPT-SC schema and I would recommend all the listeners to take a look at the schema. I have personally utilized the schema many times when I'm on boards. So it is anatomically driven.

that the most common cause of hemoptysis in general are bronchitis and bronchiectasis. Now bronchitis either comes in the acute flavor or chronic flavor. and by and large most of the people who have bronchitis either they have acute onset of viral infection or they have chronic bronchitis from let's say COPD.

then you go down the path of bronchiectasis and bronchiectasis has so many potential causes but bronchiectasis is one of the important causes of life-threatening haemoptysis because the bronchioles get their arterial blood supply from the bronchial artery which is like a high pressure arterial circulation. So it's always something which makes clinicians worry. This patient can decompress it really fast. And then we go down the lungs, you will find that people can have endobronchial lesions.

like tumors let's say either vascular tumors or foreign bodies which can cause hemoptysis and then in the lung parenchyma you can have cavitary lung lesions which can cause hemoptysis. At the microscopic level you can have pulmonary capillaritis.

and that's the different schema of diffuse alveolar hemorrhage and in the DAH schema there are so many potential causes like there are vasculitic causes and non-vasculitic causes and under the non-vasculitic causes one important bucket to consider is the cardiac causes because you could imagine that when your heart is not functioning well often the pressure in the pulmonary capillaries can rise and that can end up causing hemoptysis and the reason why i am bringing this up is that in

our patient although all the causes which i mentioned are possible so far and we will have to think more to figure out which one of them fits best but in the history we have this evidence of bioprosthetic valves now often although Noah told us that he didn't hear any unusual murmurs but sometimes it's difficult to hear the murmurs from the bioprosthetic valves so

It is conceivable that if the valve is not functioning well then the pressure in pulmonary capillaries can go high and it can end up causing hemoptysis and also this gentleman has paroxysmal afim so which can also cause left atrial remodeling.

And that could further contribute to the possibility of hemoptysis. So I'm keeping the left atrial problems at back of my mind, which could be causing hemoptysis. Now, if we take a step back and then layer on to what Mark was saying in the first aliquot that.

is it possible that this gentleman has let's say ACS from endocarditis and which would explain the fever and chest pain right so now that we have our prosthetic wall that hypothesis is kind of reasonable to at least entertain that maybe this person had

endocarditis and which ended up causing fevers and cough and maybe through some septic emboli to the lung parent chemi as well so although that is more common in the right side if you have right side endocarditis but it can happen at left side as well now

What are the other possibilities which you can layer upon? So another common thing is that maybe this person has let's say pneumonia or lung abscess and which is a very common cause of hemoptysis fever and cough and this chest pain like as we said that it's not very sensitive whether it is crushing or stabbing kind so maybe that lung abscess or pneumonia itself is contributing to the chest vein so that will be my thought process going down the anatomical pathway

and then figuring out that where is the localization. I love that, Kirtan. That was such an awesome schema on homoptysis and such a great job how you layered in the foreground and also the patient's background into that homoptysis schema. So I love that. Yeah, I'll say just practically too, I feel like anytime I see a patient with hemoptysis, one of the first things I also do check is their nose as well, because I've been fooled a couple times.

And patients that have, you know, pretty significant epistaxis that are swallowing their blood and then also coughing it up. And you can think that the patient's having hemoptysis, but they're actually having epistaxis, which really is its own differential and its own. So I always.

to ask patients about that and take a look in their nose. And then always just make sure I'm not also missing hematemesis too, because sometimes patients can confuse, you know, they're coughing or vomiting of blood. I think here we have a lot of momentum towards the lungs and thoracic cavity.

because we have cough, we have chest pain. So it makes sense that the patient's having homophysis with the other symptoms that they're having. And then I'm just thinking about, just like you wonderfully summarized here, I'm kind of summarizing this as like an acute... inflammatory thoracic syndrome centered around hemoptysis, right? In a patient with a previous bioprostatic valve. And then honestly, I'm pretty worried about this patient, right? This patient is tachycardic, they're tachypneic.

They're hypoxic. I would say the hemoptysis, at least based on Noah's description, is probably the thing that's... It always worries me, but it's worrying me probably the least out of those vital signs, you know, that I mentioned. It doesn't sound like it's massive hemoptysis, but I'm very worried about the patients, again, hypoxia, tachypnea, and tachycardia. And I'm thinking about like...

What causes of hemoptysis, if we're assuming this is hemoptysis, can cause a patient to be this sick this quickly? Bronchitis, typically being from viral infections. An immunocompetent patient doesn't typically make patients... sick this quickly, but I would definitely get a respiratory viral panel on this patient. But I'm thinking about things like cavitary lung or cavitary pneumonia, right? So patients can get like an acute staph or strep.

Klebsiella, Pseudomonas, Cavitary pneumonia, and be this sick and have homoptysis and be this hypoxic and tachycardic. So I think we're going to make a lot of progress on the chest X-ray and the CT of the chest.

Now you'll hear that anytime we hear hemoptysis, I think we're always classically thought pulmonary embolism. Like that's the one thing that we don't want to miss. And that's good because, you know, pulmonary embolisms are very deadly and they have a very high morbidity mortality. But I'll say. It's only about 10% of patients with pulmonary embolism that present with hemoptysis. So while it's good to think about, it's definitely not the most common cause.

But I think there's really not a role where this patient doesn't get a CT PE protocol. One, obviously to roll out PE, but then to just get a better look at their parenchyma. This patient's really just too sick just to stop at the chest X.

because, you know, chest x-rays can also miss, you know, cavitary lesions, especially if they're on the smaller side. So while, you know, everyone's going to get it, at least in the U.S., would likely get a chest x-ray in the emergency room, I would go right to the CT PE protocol. And Kirsten, I forever will fear prosthetic material in the body. Maybe because...

My wife's an infectious disease doctor, but also I've seen just many complications of prosthetic material, that be prosthetic joints, prosthetic valve. So anytime someone has a prosthetic valve, I just think endocarditis, endocarditis, endocarditis, right? We're going to get blood cold.

in this patient. And in addition to what you said, like, you know, obviously, if it was more right sided endocarditis, we would think of, you know, septic pulmonary emboli. But kind of layering in with you also said that say this patient has mitral valve endocarditis.

And then they have mitral valve rupture or, you know, severe mitral valve regurg. Acute pulmonary edema can also cause hemoptysis and blood tissue as well. So I definitely am going to want an echocardiogram and blood cultures in this patient. But yeah, no, I'm pretty worried. about this patient. I'm very curious where this is going next. And I'm just really excited about the chest imaging that you guys got.

I'm really excited too. And I have a question for you too. When I hear like hemoptysis, I always like think how much the patient is having like... It's something that I don't know if we can measure, but how you two deal when... And when had a patient with this complaint and to try to figure out if it was a lot, if it was not too much, you try like to ask a question or something like to make more easy for us to understand.

How has that happened? Because I think it's something that we cannot have dimension or, I don't know, have control to know about it. Because I think if a patient sees blood, probably starts to be scared and go to the hospital. Do you guys have any tips for that?

Yeah, that's a great question. I think you'll see this commonly asked on like, you know, board questions, and then also see them like different algorithms, say like an up to date algorithm on what, you know, defines like massive homoptysis, but I think nothing beats the clinical.

assessment right going to the bedside and seeing if a patient is in distress and how humanically stable they are right so if i walk in a patient's room and they're you know sitting on the edge of the bed tripodting i see their vital signs they have a softer blood pressure they're very hypoxic, right? They're very tachycardic, and I see them actually coughing up blood. I don't

I'm not going to care about how much really that is. I'm just going to activate like my massive hemoptysis kind of treatment algorithm and really support that patient's like hemodynamics and their airway. Now, I think sometimes. when I talk about this I'll say that like if someone I'll ask someone like have you been cut

coughing up cups of blood, as opposed to just streaks of blood. That's sometimes a way that I differentiate. But I think honestly, at the end of the day, just that kind of bedside assessment of a patient being sick or not sick is the most helpful for me. But I'm curious.

helpful for you no i agree with you that when i was intern i also used to asked i used to get asked this question by my icu colleagues that they will quantify that you need to have like 50 ml in certain hours or like let's say 400 ml over last 24 hours but you could imagine that it's so cumbersome and like how can you keep track of each and every time

patient is coughing sometimes patient is so uncomfortable that they will end up coughing not in the cup you gave them but just outside right maybe they are in the washroom when they are having this coughing fits and how can they cough in the cup which you gave you so this quantity

never matters and what mark said like i have seen patients who have just literally sticks of hemoptysis but then literally one hour later they start collapsing their work of breathing gets crazy you get the abg or vbg and they are severely hypoxic next thing you know they are intubated and next day they have like one liter of blood pulled out of them in form of DAS right so like blood can stick around in the lower airways and it may never come up

so you would be fooled into thinking it's just like GI bid right there's so many people do not have like overt like melina or something but you look at their hemoglobin and it's like six right so where did all that blood go because it's still in their system maybe the patient hasn't pooped yet right so similarly like

you sometimes we have seen that there is a massive blood clot which is in the bronchi which is literally causing wheezing and which is choking your airway so no blood is coming out because you have blocked the bronchi right so

Often the clinical judgment takes precedence. So in this our gentleman who is like severely tachypneic hypoxic and I'm sure that when they did the ABG it would saw some signs of like hypoxia or hypercarbia so i would be more worried about intubating this patient rather than not intubating it was very nice hearing kirtan discuss it because he kind of telegraphed this patient's clinical course

So for some workup and additional information, his initial CBC, WBC count 14, hemoglobin 14, platelets 140. CMP was normal, except for creatinine of 1.2. from a baseline of 0.8 a month ago. EKGs were normal, no signs of ischemia. His troponin was 83 and then slowly downtrended. His NT-pro BMP was 2000. And as those labs were coming back and as the bulk cultures were being collected, the patient started decompensating from a respiratory perspective. He was put on a non-reparietal mask.

and he was still hypoxic so he was ultimately intubated and sent to the ICU. In the meantime he also got a CTP scan which didn't show any pulmonary embolism but did show some peribronchovascular consolidations and bilateral pleural effusions. In the ICU, they're able to get a quick echo, which show moderate prosthetic MR, mild to moderate...

prosthetic mitral stenosis with a normal LV ejection fraction. Those echo findings weren't too far from the patient's baseline from about a year ago. Wow, now this patient... I took a turn. I'm very sick. I feel very bad for the patient, but a very interesting case. The only just two questions I have for you now is what was the baseline hemoglobin and baseline platelet count? So his baseline hemoglobin was around 14, and his baseline platelet count was around 220.

Okay, awesome. Thank you. And maybe you can just go back and forth because there's a lot of data here. Maybe I'll start to talk about the initial lab first. And then I would love to hear you chime in as well. But, you know, I would say in terms of this, I'll talk about the CBC and BMP, right? The CBC.

has a neutrophilic leukocytosis. I don't think any of us are surprised by that, right? This patient has acute thoracic inflammatory syndrome. We really expected a neutrophilic leukocytosis. So I'm not surprised by that. You know, the hemoglobin being normal, you know, that does not rule out DAH. There's a, you know, I want to say there's about like a 10 or 20% of patients with DAH that actually don't have a normal hemoglobin at start.

We might check the hemoglobin tomorrow and it might be like much lower. So I think it's very important to trend the hemoglobins in this setting. And I think we've all been taught a similar concept in GI bleed, right? Say someone. Say someone is having an active GI bleed right in front of you. If you check their hemoglobin.

because they're losing whole blood, the hemoglobin actually might be normal or what it was prior. But then if you check it hours later the next day, then it might be much slower after there's a fluid shift. So we're going to keep a close on that hemoglobin. And then, you know, this patient, you know, has a mildly decreased platelet count from their baseline, right? So they're about in the 140s from a baseline in the mid 200. So I'm definitely going to track that.

you know, as we probably cure them, we'll probably talk about because I know one, I think we're both thinking about and two, he loves diffuse LA over hemorrhage, you know, there's definitely some autoimmune diseases that have a propensity to cause thrombocytopenia. Right. So I definitely want to keep a close sign that platelet count. And then for the basic metabolic panel, I think the thing that I'm keeping my.

uh close cyanide is the kidney function right this definitely isn't a significant aki but it definitely is an aki i think the first thing i'm going to want right away is the urinalysis right it wouldn't be surprising if this patient being sick for a week was having decreased oral intake because they felt ill, and then just had a prerenal AKI from hypovolemia, right?

And so I definitely want that urinalysis because, you know, say maybe we give the patient fluids and we check the creatinine tomorrow. It's totally normal. Then that's likely a pre-renal AKI. And that's not really part of the diagnostic problem we're trying to solve. But if we get the urinalysis.

and it shows hematuria, proteinuria. Now we're building a case for possibly a pulmonary renal syndrome. And, you know, there's many causes of pulmonary renal syndrome. I'd like to tackle that part. But I would say, Noah, the things that I'm keeping my eye on right now is that... I really want to turn that hemoglobin.

I'm marking the platelet down as possibly either signal or noise for the final diagnosis. I really want a urinalysis to see if there's an active urinary sediment. And then I'm glad the patient, at least the EKGs, the troponin, there's really nothing going for.

coronary syndrome at this moment, which really, with everything else going on, that was much further down the list. After you revealed more data, but it's always good to roll it out. And then, you know, the last thing I'll just mention is the NT-BRO-BMP. You know, in the setting of an acute, you know, thoracic syndrome, like.

and an AKI, a lot of times some patients can have an elevated, you know, antipropion P. It's always important to compare it to their baseline. So maybe this patient with, you know, atrial fibrillation, atrial fibrillation at baseline, and especially when you have AFib with RVR.

can increase your NT pro BMP. So I'll be very curious about the patient's baseline, but... um i'm not overly surprised about again another thing that i'm tracking and i'm glad we got the echo um that didn't show at least any dysfunction of the mitral valve and honestly no based on the description of the ct chest it didn't show like there was

really strong evidence, I guess, for pulmonary edema. There wasn't a lot of interlobular sexual thickening, a lot of GGOs. There was bilateral pleural fusions, which, again, is another thing to track on the problem list, but... For now, I'm just going to keep it as another thing to think about. But yeah, Kyrton, what are you making of with this initial data and then also like with the CT scan as well?

Perfect. Thank you so much, Mark. I must comment that, you know, you said that your power, the invisible power that we'd like to have is like flying. And I must say that if you.

do end up flying you would be an eagle you know because your bird's eye view is still so sharp that you covered so many things you know and still tackled everyone so thank you so much for that so i agree friends that if we just create a problem list then what we have we have like a 61 year old gentleman who has like one week of symptoms and the big things we are tackling is lung findings on the CT scans which is a bronchovascular fusions, hemoptysis, possible AKI

and possible thrombocytopenia and we're trying to figure out if there is a unifying cost or at least if we can make progress in the long aspect which is the elephant in the room right now right so for the lungs i was thinking that maybe i can tackle the causes of what we are seeing in terms of infectious autoimmune neoplastic iatrogenic causes and then while we are discussing that

causes we can try to find the overlap with the AKI overlap with thrombocytopenia. So common things being common and I think this is what Mark was asking in the first eliquid that he would like at least the respiratory viral panel right. Because whenever we see the peribronchovascular markings, it's kind of non-specific. And to be honest, any virus can do it. So common things being common like influenza, parainfluenza, respiratory syncytial virus, adenovirus, any of them are a fair shot.

Although the viruses may not have such dramatic lung findings but you could imagine that once you have viral infection there is always a chance that you will have superimposed bacterial infection because many viruses kind of impair your mucociliary clearance and predispose you to secondary infection. getting the RVP would be the first step. Now if we go down the bacterial category then what kind of bacteria can do this? At least we are not able to see any

big consolidation, any lung abscess, which would make us wonder about strep pneumonia, pseudomonas, clepsiella, the classic organisms. But the atypical organisms, classically like legionella, mycoplasma, can definitely end up causing peribronchovascular. markings and consolidation. So I would keep those at the back of my mind and legionella specifically because it has propensity to cause real AKI as well as thrombocytopenia. So I'm tracking that. What about some fungi?

so in the fungal category although pjp we are classically taught that not to cause diffuse ggos but it depends on how good is your immune system so it can still end up causing such long findings actually as we have in our case so i would like to get HIV, syphilis, and hepatitis serologies as the part of basic workup. If I go down the path of the rare infections, like zoonotic infections, and this is where I want to layer on the thrombocytopenia category more.

that oftentimes when we think about the tick-borne infections which can cause some percent of penia you might be wondering that well why don't they have other classic findings or why don't they have systemic features why don't they have like any evidence of tick bites on their skin well often time it happens it depends on how do you acquire those organisms so if you inhale let's say leptospira then you might end up getting sore throat and dh similarly

although tularemia can end up cause lymphadenopathy and skin rash if you inhale the tularemia directly you can get hemoptysis as well so what are the infections i'm thinking about so tick-borne that would be rickettsia, alrechia, anaplasma and babesia and what about other rat-borne infections I would be thinking about leptospirosis, hentavirus and Other rare zoonotic infections would be tularemia.

All of this can end up causing thrombocytopenia as well as hemoptysis depending on the mode of acquisition. So I would like to know, I would go to the bedside, ask the patient any other pertinent risk factors, any exposure to water, exposure to pets or not. Two other infections I wanted to mention which are on our actually DH schema. One of them is VZV and another one is trungyloids. Now both of these infections have propensity to get in your lungs depending on

How good is your immune system? So if you're immunosuppressed for any reason, VZV and trondyloids can end up causing DAH. So I would be keeping those two things at the back of my mind. Now let's switch the gears and go to the rheumatology bucket. So Mark already laid the framework for us that this AKI could be pre-renal in nature given the fact that patient probably is not eating well, patient literally has so much volume loss in terms of this hemoptysis.

But what if it is real intrarenal AKI and maybe the UA can corroborate the same for us? Then the big categories I would be thinking about is ANCA-associated vasculated TDS because again... Remember that anchor is vasculitis which involves your pulmonary capillaries but it can also end up involving pulmonary arteries as well and it can cause bronchovascular sheathing rather than the classic DAH which we are expected to see every single time.

So I will definitely get the NCAR serologies then SLE can have so many different forms although we don't have any other classic findings but DAH as an index presentation of SLE is also not unheard of and given the base rate it's reasonable to get the ANA as well.

possibility would be good pastor's disease which is the antiglomerular basement membrane disease which can affect both your capillaries in the kidneys and the lungs so i would like to get that as well now what about the heart part so we were initially thinking that

left atrial dysfunction, mitral dysfunction can end up causing this regurgitant jet and that is sometimes known to cause so-called bland DAS that without inflammation. Now although Noah told us that There is nothing there is no change in the degree of regurgitation of synosis from the baseline but we have to understand that this gentleman has a bioprosthetic valve and the sensitivity of TTE in quantifying the structure of valve.

may not be ideal and often times you might need advanced imaging studies like let's say transesophageal echocardiogram and even cardiac PET scan to definitely glean at the valvular structure in a better detail so and although we don't have

classic findings of formular edema. I'm still keeping that down in my list so that we don't miss that cause because in history it is glaring at us. Now the last part, the iatrogenic part I wanted to mention was that Although Noah told us that there was nothing of relevance in the past, like social history or recreational history, but I would still ask the patient if there was any kind of inhalational exposure, like cocaine, marijuana.

any passive smoking or any let's say electronic cigarette related stuff because all of this can end up causing various forms of lung injury including let's say hypersensitory pneumonitis, DAH and even organizing pneumonia kind of stuff. So I would like to know if this patient had any of these receptors. And maybe I can quickly ask Mark again if any other thoughts that he had while I was discussing and then maybe we can ask Noah to give us more data.

I don't have any more thoughts. And I always learn so much from listening to you. But I will do I will say that, you know, when you're talking to because you're teaching me so much, it does trigger.

other thoughts in my mind. And I also was thinking about the pleural fusion as well, because I think that's an interesting landscape to think about, because, you know, especially a lot of the rheumatological conditions, I think a lot of us at first think of like anchor associated vasculitis as kind of the prototypical

renal syndrome with DAH, you know, ankylosociovasculitis doesn't typically cause pleural fusions in its classic form. And those pleural fusions that were on the CT chest that no shows were pretty significant. So I'm kind of thinking about, you know, while we're laying in this. you know, peribronchovascular infiltrates that we think are possibly DAH, but, you know, we're evaluating for other infectious causes that you mentioned.

this, uh, AKI and this cardiac history, like what is our kind of overlap of everything that's going on? Right. So pleural fusions, you know, big things to think about are like the three organs, right. That can cause volume overload, right. The heart, the liver, the kidney, you know. We got our transthoracic echocardiogram, right? That didn't show, we didn't hear a radial pressure, but it sounds like if Noah didn't mention, I'm assuming the radial pressure on the echo is probably normal at three.

So we don't have really a lot going for at least a cardiac etiology of volume overload. I'm not necessarily saying that we don't have, you know, evidence for endocarditis, because I think we'll have to wait for the blood cultures and possibly advanced imaging, like Kyrton said, but I don't think we probably have. a heart failure resulting in pretty moderate sized pleural fusions, right? I think when we get the urinalysis, I'm definitely gonna play close attention to

the protein rate. And I'm definitely going to quantify if there's any protein to a urine protein to creatinine ratio to see if this patient has significant proteinuria and possibly nephrotic syndrome that could be leading to, you know, significant pleural fusions.

It doesn't sound like we have anything going for the liver, right? We don't have any really signs of, you know, cirrhosis that we can blame, you know, pleural fusions on. But the other thing I'm thinking about when we think of the rheumatological bucket too is just cirrhositis, right? rheumatological conditions that can result in serositis and DAH, right? So things like lupus, right, for instance, it'd be...

Probably a little more atypical presentation of SLE, but SLE can definitely cause DAH and serocytes to lead to pleural fusion. So like I said, I think those pleural fusions are interesting. I definitely want to see how much proteinuria the patient has. And then, you know, if the patient doesn't have much... I wonder if we're dealing with some like serosal inflammation. It also would be kind of atypical for an infection to cause pretty.

bilateral symmetric pleural effusion, you know, you certainly can get unilateral paranormal effusions is extremely common. And that's probably one of the most common causes of the unilateral pleural effusion. But to have bilateral symmetric pleural effusions from an infection is definitely a little less common.

But, you know, I would just say practically speaking, given how sick this patient is in the ICU, all patients like this are going to get broad spectrum antibiotics, you know, targeting MRSA and pseudomonas for severe. pneumonia just because of the morbidity and mortality is so high. So a lot of these patients will probably get vancomycin and either piperacillin, tazobactam.

or cefepine, in addition to azithromycin for atypical coverage. So that's going to be happening on day one in the ICU. But I'm really excited to kind of to hear about the additional investigations that Kirtan mentioned. Back to you, Noah.

So this patient went to the ICU and he was not doing well. He was put on pressures and he was on maximum vent settings. They sent off a very broad infectious workup and they also started, like Mark said. very broad antibiotic coverage and vasopressors for the patient. So HIV, hepatitis, syphilis were negative. Diginella was negative. Blood cultures resulted negative.

All the workup for tick-borne infections were also negative. Here in St. Louis, we have a lot of rhodochia and anaplasma, so those are always in our minds. The patient underwent a bronchoscopy, which revealed DAH. like we were suspecting. And they actually sent a PCR for all the infections that Curtin mentioned. Leptospirosis, antivirus, and VZV, those are all negative. I know Mark is dying for the UA.

And the way is with 50 RBCs, more than 50 actually, some trace protein, and the UPCR is 300. So this patient was critically ill. it wasn't improving with broad spectrum antibiotics and the initial infectious workup was coming back unrevealing. The team decided to pull the trigger on immunosuppression and he underwent.

post-osteroids, and two sessions of plaques. Given the patient's worsening respiratory status, he was transferred to my hospital, which is an ECMO-capable center, for consideration of ECMO. while he was receiving immunosuppressive and while his lungs had a chance to recover. Upon arriving to my hospital, the biggest notable finding among his labs were that the platelets downtrended to 73,000.

Nephrology was consulted, rheumatology was consulted, and they decided to stick to the plan of continuing the post-dose steroids and the PLEX sessions. Nephrology also wanted a renal biopsy for confirmation of... possible pulmonary renal vasculitis. In terms of his rheumatological workup, his C3 and C4 were low respectively at 55 and 7.3.

His CRP was 13.6. His rheumatoid factor was less than 10. His ESI was 32. His ANA was negative. His double-stranded DNA was negative. ENA negative. ANCA was negative. Anti-GBM was negative, MPO was negative, PR3 was negative. Notably, all those labs were obtained upon arrival at my hospital after post-dosteroids and after PLEX. The outside audioimmune labs were still pending at time of transfer. Wow, what a turnover. Kirtan.

Do you want to share your thoughts about the case? Perfect. So thank you Noah for giving us all the data. I could imagine it's a very complicated case and it's commendable that you guys took care of this patient and did good for this patient. So, so far, what are we dealing with? So initially, we were, this centermine is hemoptysis. We were trying to figure out the causes and eventually on bronchoscopy, we confirmed that it is diffuse alveolar hemorrhage.

and further labs have suggested that the UA had active sediment which means we are considering possibility of glomerulonephritis and the labs show that the platelet keeps on down trending. an extensive set of infectious workup and the rheumatologic workup so far has not given us the final diagnosis. Now let me first comment on this rheumatological workup part and then maybe I can ask Mark to

tell us more about this thrombocytopenia aspect. So these labs were taken once the patient had already underwent the plaques and steroids. Now in general you don't expect the antibodies to suddenly become negative.

it can happen in some let's say rare hematologic causes of vasculitis that maybe after doing the plaques you were able to take out let's say ADMTS certain inhibitors and maybe now you cannot diagnose CTP or something but in terms of ANA, ANCA, even after plaques maybe they won't be falsely negative.

But having said that it is important that many cases of encastrochial vasculitis are seronegative. So only way to diagnose encastrochial vasculitis in such cases is by biopsy, like renal biopsy or the lung biopsy. So I'm still keeping... on my mind the possibility of vasculitis although the serologies were negative. Now the fact that complements were low kind of makes me move away from ENCA and IgA vasculitis because both of them tend to cause normal complements.

as long as they are present in isolation. If there is a secondary factor going on in the body then maybe complements could be low but they don't tend to cross complements low. Then the question becomes that is this lupus which can cause immune complex mediated glomerulone aphritis or Is it something else which is non-rheumatologic, which is causing immune complex formation? So those entities would be endocarditis, something which we have been suspecting from the onset itself.

Some drugs can do it, but there is no suspicion of any iatrogenic drugs or any recreational drugs. And hematologic malignancies like lymphoma, leukemia.

including multiple myeloma are known to cause immune complex mediated glomerulonephritis in by terms of antigen antibody complex formation so how to make the progress so although the blood culture so far have been negative but what about so-called fastidious organisms or culture negative endocarditis kind of workup so given that we have prosthetic valve we know that these people are at heightened risk for this unique infections so i would

definitely like to get the help from the infectious disease colleagues to see if we can get the PCRs and antibodies both because we know that if you just get antibodies and not PCR then maybe the sensitivity is not that good i would like to check for bartonella brucella coxiella and other like classic has set group of organisms to see if anything turned out from that aspect And now maybe I can ask Mark that how he is putting together all of this along with thombocytopenia and burgeoning status.

Yeah, that was a beautiful summary. And I echo your concern about culture negative endocarditis. I think Robbie has taught us that really anytime you before you pull someone with steroids, and I'm not saying that's the wrong thing to do whatsoever, but it's just something that now is a reflux for me.

Anytime you pull someone with steroids that you're concerned for glomerulonephritis, just make sure you check those complements, which they're always checked in these settings. But if those complements are low, always consider, can this be? culture-negative endocarditis-associated glomerulonephritis, right? Because if you give someone with coxiella, post-losterase, that can make things a lot worse.

You know, most of those bugs that, you know, the three most commonly zoonotic organisms that cause culture negative endocarditis being like here at the mention, Coxiella, Brucella, Barnett. Bartonella, most of those, there's not really a high association with diffuse alveolar hemorrhage. Now, if the patient had, again, like we mentioned in the first Alquant, if the patient had culture negative endocarditis,

issues with their mitral valve, and then they have like acute pulmonary edema, right, leading to diffuse alveolar hemorrhage, that would be bland DAH, not capillaritis, which Kiersten talked about. That's possible. But it seems like the mitral valve is... At least if someone had such high degree of pulmonary edema that it's leading to intubation and a diffuse hour hemorrhage.

You probably would see some sort of abnormalities on the transthorasso echocardiogram. You might miss a vegetation for sure. And I'll say most of the time, we do miss vegetations for culture and negative endocarditis on TTE. But I agree with Kirith and I want advanced. Probably if we're able to, this patient's very sick, but a lot of times, even when a patient's intubated, sometimes we can get a transesophageal echocardiogram to see how the mitral valve is doing or a PET scan.

PET scans, PET CTs for endocarditis actually perform pretty well for prosthetic valve endocarditis. I'd be very interested in that.

Because I'm just very worried about that prosthetic valve and those low complements. But sorry about that tangent, kids. I just wanted to mention that, that again, low complements, glomerulonephritis, just make sure it's not endocarditis related at glomerulonephritis. But in regards to the platelet count, you know, thrombocytopenia in critical illness is so common. So I would say most commonly a patient in the ICU that's getting a lot of antibiotics and is in septic shock.

A huge proportion of those patients develop thrombocytopenia, but, you know, let's layer it, layer it into our. problem representation, right? I would say that APLS is sometimes the forgotten cause, I feel like a diffuse alveolar hemorrhage. It's definitely something to consider. You know, APLS usually isn't super hyper inflammatory, right? patient had a week of fevers.

a week of fevers and kind of, again, like inflammatory thoracic syndrome. Now APLS can be inflammatory if it's secondary APLS associated with other autoimmune diseases. So for instance, if this patient has SLE and they have APLS, they can get...

you know, DAH from their SLE, but also DAH from APLS. So I would definitely probably send APLS labs in this patient, but I probably have a lower suspicion. But what I was getting is that APLS can also cause thrombocytopenia, right? So it's something to consider. APLS can cause thrombocytopenia. through many mechanisms, just on its own, or through a TMA, a thrombotic microangiopathy. So, like I said, usually in the ICU, it's, you know, critical illness is very common, but...

You know, I would work it up further by doing usually everyone with severe thromocytopenia. I'll get hemolysis labs to make sure there's no evidence of destruction. DIC labs as well. Again, further evidence of destruction. I would love a blood smear to see if there's. anything abnormal on the blood smear.

Um, also a patient in the hospital, I doubt this patient, I, this is probably not even worth saying, but was getting heparin products given they were having, um, DH, but you know, sometimes a patient might accidentally got heparin. So, um, I would definitely check if the patient got heparin and make sure that heparin induced trauma. cytopenia is not also decreasing their platelet count. Why are they in the hospital? So yeah, and then, you know, really,

The rheumatological causes, again, care that I'm not too familiar with really ANCA-associated vasculitis on its own, maybe through secondary, you know, etiologies, but really on its own causing thrombocytopenia. But I think in the DAH, thrombocytopenia overlap in terms of rheumatoid. I'm really thinking about SLE, APLS.

Not really cryoglobulinemia or Bichette's. Yeah, I think that those would be my main, at least, rheumatological causes. But I would always, again, make sure that that patient is not hemolyzing, having DIC, check a smear.

And I would kind of go from that, yeah. No, Mark, I agree with you that in acute illness, many times that we go down this rabbit hole of figuring out what is causing thrombocytopenia, but then... extensive workup eventually is negative and as the patient gets better platelets kind of get better on their own as well and especially when platelets are not severely low i know they are kind of downtrending but if platelets are like let's say five

or like 10 then definitely i would be very suspicious of something sinister going on and i would run before it but right now 70k we can still focus on the bigger picture and regarding the comment which you made that in general vasculitis let's say anchor tends to cause thrombocytosis because of inflammation so i remember there was one one of these vmrs where we discussed that if you have autoimmune diseases especially vasculitis

along with cytopenias then first consideration should be are there any medications just like how you have related radicardia first thing you think about is beta blockers so similarly when you expect radicards to be high and if they are low think about medications is the patient with any kind of immunosuppressives is the patient that's taking

cocaine with levamizole and levamizole can sometimes cause fervocytopenia by terms of agranulocytosis and lastly given that this patient is older and I know that we don't have any other signatures in terms of MCV but Over the years we have refined this thinking and we know that Vaxos syndrome does not necessarily present with high MCV.

And so many people who are diagnosed with, let's say, giant cell arthritis or NK associated vasculitis or inflammation in the lungs, eventually they turn out to have VACs. So since there are cytopenias, at least thrombocytopenia i would still keep like this big category of vexas at back of my mind if all infectious workup is negative and patient is not turning around then down the line we can think about that and also since this patient is too sick i would also like to get the

Paraproteinemia workup just to make sure I'm not missing an N spike. which can sometimes end up causing glomerular nephritis and weird things can happen with M-spike. So I would still like to get the M-spike. And yeah, Noah, would be enlightening to hear from you any further this culture negative workup, which Mark was mentioning, if we got it.

The last thing I just want to mention, because I just want to emphasize this, because this is something I've really paid attention to as I gain more experience, is that you're really just the... characteristics of the test fee order, right? And so I'm so glad that you mentioned that, you know, there's a significant proportion of patients with encovasculitis that have negative enco serologies, right? It's more common to have enco positivity and GPA, right? About 90% of patients.

will have ANCA positivity. But there's some, you know, studies that show you almost like 50% of patients with MPA can have a negative ANCA serology. So I think it's really important to just to know what's the sensitivity, what's the specificity of some of these tests.

we're ordering, especially in this critically ill patient, and just to help tailor your post-test probability. And I think, no, a patient like this too, if there's family around, obviously, unfortunately, we can't talk to the patient, but I would love to hear from the family. Hey, does this patient have a history of chronic sinus issues, right? To make a...

to point towards GPA, right? Does this patient have a history of asthma to point towards eGPA? This case doesn't really fit well with eGPA, but I'm just saying I would do some of that targeted review of systems for at least the family to see if there's any hint at the... uh vasculinities but yeah very very interested to hear more this discussion is so rich it's giving me a headache i'm gonna have to go back and re-listen to this podcast episode many times because

I feel like you all are extracting so much information from this case, information that I didn't even think about. So that's superb. That's so amazing. I do have some more information that you all requested.

As far as the isimoglobin, it downtrended up to 8 and then kind of stabilized around 8 and 7, between 8 and 7. This platelets downtrended to 50 and kind of stabilized between 50 and 60. His DIC labs, his INR was 1.6, his PTT was 23, his fibrinogen was 54, and his D-dimer was more than... 128 000 which is the upper limit of detection in the lab when he got here we were also concerned about endocrinitis so they asked for a repeat echo and the repeat echo

actually didn't show any signs of mitral regurgitation nor mitral stenosis. And the outside echo was reviewed by our cardiologist, and he confirmed that there was mitral regurgitation and mitral stenosis in the previous echo. For the culture negative endocarditis, coxiella was obtained, which was negative. Bertonella and bricella were not obtained. For the hemolysis labs, those were all negative, and this mirror was unrevealing.

The patient underwent renal biopsy for confirmation of the suspicion of a pulmonary renal vasculitis. The kidney biopsy showed acute pubular injury. thin glomerular basement membrane consistent with Alport syndrome, global glomerosclerosis, interstitial fibrosis, minimal, and some atherosclerosis. which was actually not consistent with fast ladders Wow. Thank you so much, Noah, for all this information. So Mark, what all this add for you? Where are your differential now?

Yeah, I'm going to kind of talk about a lot of the pertinent negatives and then I'm going to hand off the renal biopsy to our... expert glomeropathologist, Kyrton Batolia. But yeah, you know, I'm glad that Noah's team got to look at the echocardiogram and scrutinize that a little more. It seems like really, at least from the transthoracic echocardiogram, this really knows.

concerns for any acute valvular pathology. So it definitely makes me feel a little better about the lower likelihood of a culture negative endocarditis leading to a glomerular nephritis. You know, I think, you know, I mentioned that we did get Coxiella serologies. I definitely would still want Bartonella and Brucella serologies as well, just to kind of, you know, finish off the kind of three most common zoonotic diseases that present.

culture negative endocarditis. The other thing that I thought was interesting was some of the coagulation parameters, right? This patient had, I believe, an INR of 1.6 and a very low fibrinogen. It doesn't sound like there was a smear consistent with schistocytes, and it doesn't sound like there was hemolysis labs that were consistent with hemolysis, but it sounds like this patient might have, you know, disseminated intravascular coagulation. You know, there is a DIC score.

that we can use, that you can use on MDCalc that helps you refine your probability of having DIC because a lot of the different signs of DIC are either sensitive. and not specific or specific and not sensitive. So if you put together

the coagulation parameters, the fibrinogen, the platelet count, then it gives you a score. And this patient would probably score pretty high because, you know, hypofibrogenemia is a pretty specific sign for DIC. You know, patients with liver disease can have low fibrinogen, but we're not. having any you know evidence of liver disease in this patient and sometimes there's like different congenital diseases that

wouldn't really present at this age with a low fibrinogen count. So I'm worried that this patient's having a consumptive coagulopathy. And the question really, is this the... Is this causing the diffuse allele over hemorrhage or is it a result of the patient just being?

you know, acutely ill in the ICU. So I think in these instances, you know, we really support patients with product, right? The most common triggers of acute DIC in the ICU are usually infections, which we've really ruled out most infections. in this case. And then also just critical illness and shock can lead to DIC as well. There's kind of more subacute and chronic causes of DIC. Sometimes that cancers can cause them more.

subacute to chronic DIC picture, prostate cancer being the most common, but really nothing going for that here. So I think in this instance, you're really just going to support this patient.

with product to improve their coagulation parameters and their platelet count, especially given their bleeding, and then see if their DSC improves once their critical illness improves. But, you know, Kirsten, I think really here... um all of the money is in the renal biopsy so i'm very curious about what you think of the renal biopsy perfect thank you so much mark for

giving us a broad overview of what infectious workup still needs to be done and how we may get a diagnosis from that. So the renal biopsy, we were obtaining it from the perspective of it telling us if there is a possibility of pulmonary renal syndrome and evidence of glomerulonephritis either chrysantic or non-chrysantic but some evidence of vasculitis but

The renal biopsy was kind of a surprise and there was no evidence of vasculitis on it. What we did found was there was thin basement membrane and as Noah told us it could be consistent with Allport syndrome. So now what we know about Alport syndrome and thin basement membrane disease that both of these diseases are kind of similar to each other that they have a problem with type 4 collagen which is one of the component of the basement membrane and that's why

often these people tend to have chronic lifelong hematuria and sometimes they don't even have progression to end-stage kidney disease but in some cases they might end up having progressive proteinuria and eventually ESRD as well. In our case

we didn't have any kind of background data if the patient had like hematuria for years and years along but from what i can remember and maybe mark can correct me if i'm wrong that albert syndrome in general tends to affect your kidneys tends to affect your eyes and in some people their ears like so they can have hearing loss they can have some lens changes but in general they don't tend to affect the lungs prominently

Even if they might have caused some subtle lung changes, but it would be hard to imagine that someone would be this sick and this much evidence of BAH from thin basement women's user Alport syndrome is just not one of the classic features. How do I make the progress? Maybe we will say that the kidney injury is something which may not have final relevance to what was diagnosed in the lungs. So we will accept the kidney pyopsy, but...

Probably the more workup still needs to be done from the lung perspective. And what Mark said, all those infectious studies, BAPLS studies and down the line, even... maybe the biopsy of the lungs if needed to figure out that what is going on at the level of hormonary capillaries and other infections I was thinking to round up the discussion of Mark that

which Noah hasn't given us yet probably is maybe the parasite like strongyloid so just to make sure that we don't miss it although it would be kind of unusual for strongyloids to it can definitely cause this but then we will have to explain the thombocytopenia part separately or maybe it is just part of critical illness it's hard to say uh what do you think about any other infectious any other final touches that

No, I totally agree with you. Really, this case is, I would say, incompatible with Alport syndrome. Alport syndrome doesn't present in an acute manner, like you mentioned, in an acute inflammatory manner. And then also, you know, just for good measure, I would ask the family, you know, has this patient had, you know, bilateral sensorineural hearing loss, which is also very common.

you know, elderly adults, but you know, if they say that, you know, they had hearing loss since they're a young, a young adult or a child or, you know, any ocular findings, but you know, it's just not an acute disease that presents in this like hectic, acute inflammatory way. So

And I'm also glad that we got the, you know, anti-GBM antibodies as well, because, you know, the PEPA physiology is very similar. But again, anti-GBM as well is an acute inflammatory, typically disease and really just an isolated pulmonary.

renal disease. But Kieran, I totally agree with you. Like, strong aluities, I think, is something... I am now thinking about a lot more as I feel like I see a lot of patients with eosinophilia and I've been sending a lot more strontoloides antibodies and I've seen actually so many strontoloides antibodies that have been positive in the Bay Area and have treated a decent amount of strontoloides now.

So I think anyone with DAH really should get strongyloides antibody sent. I don't know how well that would fit. Um, really with the renal findings, I don't typically think of strong deludes as causing really a prominent glomerulonephritis. So, but you know, Hey, uh, you know, patients can have as many diseases as they want. Right. So, but yeah, Kirtan, are you familiar with, um, like. Strongolodes presenting as like a glomerulonephritis, per se.

No, Mark, you are right that in general, from what I know, cystosomiasis is more reported to cause immune-complex-mediated gumboine arthritis. Trondyloids, I am not aware of, but probably even if it did,

at least in our biopsy as Numa told us that there was no evidence of domino-naphritis so you are right that it would be hard to explain the renal aspect from it unless maybe the renal biopsy was like false negative and it missed some kind of staining to be done but you are right i am not aware of

a concrete association. All right, now we're dying to know what happened to the patient. So those were the very puzzling case because everyone felt very strongly it was going to be a vasculitis. And then when the renal biopsy came back negative, we were left scratching our heads. Reviewing the case and looking at the discrepancy between the echoes and reviewing the possible cause of the age, like Kerten mentioned, mitral valve problems are

a possible explanation. We consulted cardiology and they actually came by and did a bedside TEE which revealed flail mitral valve with severe mitral regurgitation and severe bioprosthetic valve dysfunction. The patient's actually scheduled for mitral valve replacement. It was supposed to go to the OR today, but... something came up with the schedule and he's going later this week. What do you think of the case?

So, Mark, kudos that we got it finally. And as we were discussing initially that we have discussed so many cases of so-called bland DH. And in fact, I remember that Ravi and Kara specifically did VMR on this. And in fact, I also, I think, presented a case probably on the podcast or somewhere that a patient just has mitral valve issues and just the flail, leaflet, there's so much pulmonary edema which ends up causing DAH.

it's kind of interesting that how people get low platelets from something unrelated and that is why mark reminded us so early on that Although we are doing our due diligence, checking the necessary infections, but more often than not, people will feel better and platelets will start getting better. So-called thrombocytopenia of critical illness, right? It has got no relevance.

although we say pulmonary renal syndrome but we have to establish that there was vasculitis in both the categories to say it as pulmonary renal syndrome because there are so many other things which mimics pulmonary renal syndrome.

It's a perfect case Noir thank you so much and again it emphasizes the point which we were saying that what's the sensitivity of test we are ordering that we got echo we can get five echoes you know we can get six echoes it's like saying that oh you know what I have a stroke let me get

five CT scans. Well, you're doing CT scans, right? You don't have MRI. So it's kind of similar logic, right? That no matter how many times you do TTE, it won't give you the same stuff and it's better to get the TEE.

or cardiac PET if you are thinking that valvular lesions are high on our suspicion. So yeah, Mark, what do you think? I have so many trust issues with transcerotic echocardiograms. I have seen so many differences between TT and T. tte and pet and obviously you know we can't get everyone a trans esophageal echocardiogram or a pet but in someone like this that has risk factors for this condition and is so sick i think they just need advanced imaging so i will continue to have trust issues

with the TTE. And I also continue to love discussing with Kirtan. I always learned so much from him and that was just an awesome journey and an awesome case note. I really wanted to bring this because I felt like this was such a... interesting and niche diagnosis is not very common to see mitral valve regurgitation causing dah and we're all also chasing kind of another zebra right pulmonary renal vasculitis

So this case was really a good illustration of victims, victims. The patient can have as many diseases as he damn well pleased. So ATN from shock, the operation being incidental. thromocytopenia of critical illness the fevers that mark is mentioning in the chat that we don't know the ideology for and they just self-resolved even though all the workup was negative so it was a really

kind of humbling case and really to keep you on your toes. Thank you so much, Noah. And now I will share some teaching points about the case. Diffuse a vellular hemorrhage is bleeding into the alveolar space due to a disruption of the alveolar capillary membrane. In this case, the mitral valve dysfunction leads to a pulmonary venous hypertension, causing capillary rupture and hemorrhage.

The cause can be broke down in three buckets, vasculitis, diffuse alveolar damage, and bland DAH. And the cardiogenic cause can be in this bucket. There's a really good schema in our website about it. And going for the clinical presentation, amoptysis cannot be seen in one third of the patients. So if a patient can... don't have hemoglobin, you can look for if the patient is having some acute respiratory failure, new bilateral infiltrates, dropping hemoglobin, and...

You can all start suspecting for DAH. And the gold standard for the diagnosis, it's bronchoscopy with ball. And in this case, of course, echocardiogram can help you find degeneration in the mitral valve, a regurgitation, an elevated left atrial pressure, and pulmonary hypertension. So a takeaway point from this case that I learned is always consider valvular dysfunction in an unexplained DAH. Causes of cardiac can be...

reversible and recognized with the help of echocardiogram. Thank you all. I hope to see you all in the next episode. That's a wrap, everyone. Thanks for tuning in. If you enjoyed this episode and want to be part of our community, join us for our live virtual morning report, where you can present the case or discuss with us. Visit our website for details. We would love to have you.