0:07 What's up, ninja nerds? In this video today, we're going to be talking about oncologic emergencies. There's going to be many of them, and I really hope that at the end of this video, you take away from this a true understanding of these. And if you do, and you like this video and it helps you and supports you, please support us. You can do that a couple different ways. Hit the like button, comment down the comment section, subscribe. If you want to take your learning to the next level, I suggest going down the desript description box below. There's a link that goes to our website. On our website, we have a lot of other things that we offer, notes, illustrations, quiz questions, flashcards, things that are really going to take you to that next level and help you to excel on your exams. Without further ado, let's get into talking about these starting with neutropenic fever. All right, so let's start with the first oncologic emergency, which is neutropenic fever. This is a really high yield one. I think that there's with no doubt in my mind that you'll be asked in some way, shape, or form a question on this. So let's build our understanding our foundation 0:56 on this concept. So with neutropenic fever it is neutropenia. So a decrease in the number of neutrfils and we'll give the exact number or definition of that and then fever. A fever is an elevated body temperature which again we'll give a number to that as well. And based upon this what this does this puts the patient at risk of very very severe infections especially bacteria which can lend to itself the risk of sepsis. So when we talk about neutropenic fever, we have to remember that the bone marrow, right? So this is our bone marrow and we have the red bone marrow. That's the really really important one. I'll write that up here above. The red bone marrow is the site of blood cell production. But the really important one that we actually care about here is going to be our neutrfils. These are the cells that play a very significant role in fagocytosis. And how do we recognize neutrfils? Just a little test of your knowledge. You have the red eosin acid there and the blue methylene blue base. So 1:57 they have kind of a mixture of that and then they have a you know a polymorpho nucleus. They have multiple different loes usually a couple three to five loes. So the bone marrow is the site of white blood cell production, red blood cell production, right? That's where you're supposed to produce these puppies. So here we're going to have some neutrfils. and neutrfils. What we know about these is that these are very very critical. What's critical about neutrfils is that they help with our first line of like I'd say your innate immunity. So in other words, innate immunity is whenever we have no need for our tea cells to get involved. There's really no antibbody involvement that's kind of triggering this process. It's not a lot of your cytotoxic tea cells, tea helpper cells. It's really just things like your natural killer cells, your uh neutrfils in this case. And so what I want to talk to you about is what happens with neutrfils is let's make this look really nice here. When these neutrfils get out of the bloodstream and they get into the 2:58 tissue space is what neutrfils are supposed to do is be a very important line of defense against different types of pathogens. And so we got a bunch of different pathogens here that I'm just using as an example. And these can get into the bloodstream unfortunately a couple different ways or they can get into the tissue spaces a couple different ways. But you can have a bunch of these, right? So you can have your gram negative bacteria, right? So these are usually going to be I'm sorry, what we talk about gram positive. Actually, we'll put gram positive and you can have things like strepus, right? Let's actually do it like this. Let's put gram positive here. Bacteria. And then here we can have staflacccusarius. It's a very common gram positive bacteria. And then you can have things like sudamonus, ecoli, klebella, all of those. And these are going to be your gram negative bacteria. Well, what neutrfils are supposed to do is they're supposed to help us by doing what? Well, what they do is they'll take some of these bacteria and they'll undergo a process where they take it 4:00 inside. They take it inside of their cell and they put it into this thing called a fagosome, right? And they break that bacteria down. So they're supposed to help with a process called fagocytosis. That's really what their job is is to help with the process of fagocytosis. And this is critical to your innate immunity, right? That is what's really really important here. So let's pretend for a scenario here that we got a problem where there's a drop in the neutrfils because that's where we get the term neutropenic fever. There's neutropenia, right? So let's say for some reason a patient experiences some chemo radiation therapy. So let's say that a patient gets chemo radiation. When that happens and maybe they're getting it because they have an underlying malignancy, right? Very very common. So if you have chemo radiation, you're hitting the bone. What that's going to do is is that's going to injure 5:00 the red bone marrow. Now the red bone marrow starts crying and you get a decrease in the function of the red bone marrow what's the red bone marrow supposed to produce neutrfils and if I destroy the bone marrow and I decrease this production of neutrfils in a patient who already has maybe a little bit of neutropenia. So this is why it's really really important patients who have underlying neutropenias like leukemias they're at super high risk. So if you have a condition where you already have neutripenia or less functional neutrfils and you hit them with chemo radiation you then decrease the number of neutrfils that are being produced then we get a decrease in the neutrfils. So usually what you need to have here is chemo radiation plus an underlying neutropenia at baseline or at least a decreasing number of neutrfils. Then what happens is if you have decreased neutrfils, guess what? This dude ain't going to be able to undergo fagocytosis. 6:00 So you're going to lead to a decrease in fagocytosis and your innate immunity is no longer going to be beneficial. So all the bacteria that are on our skin surface that are part of our gut flora, our urinary tract flora, our respiratory flora, all of those potentially if there's a break in the barrier, they can get into the bloodstream and they can wreak havoc. Now when these do that, guess what they do? They cause damage to tissue. You know, this could be through endotoxins or exotoxins, but there's some type of toxin damage. And then what happens is when the tissues get damaged, what do they do? Well, they alert the immune system. And then they start to try and alert the immune system by secretreting specific chemicals into the bloodstream. And these chemicals, yeah, they're supposed to help to alert the immune system, but what are these chemicals and what happens as a result? These are going to be things like interlucan one, things like interlucan 6, things like 7:02 tumor necrotic factor alpha. Their job is to try and go and really, really ramp up your immune response, right? And that's where we start seeing a bump in these. The problem with these is that these have a lot of effects on our circulatory system and on our hypothalamus. And that's where it's really really important. So when a patient has a decrease in neutrfils and we should actually define what that consists of to have neutropenia, neutropenia is defined as having a absolute neutrfil count less than 500 cells per microl. That is the true definition of neutropenas. You have to absolute neutrfil count less than 500 cells per microl. So patient who has maybe some baseline decreased neutrfils but it's not less than this gets chemo radiation damages the bone marrow drops the neutrfils even more they lose their ability to allow for basic fagocytosis innate immunity and again another thing with these is that they're supposed to also not just kill back uh not only eat 8:02 the bacteria but they're also supposed to release things like reactive oxygen species and so it's not just fagocytosis but we'll talk about this later it's a decrease in other things because they release things like reactive oxygen species and proteases and these and even things like nets neutrfilic extracellular traps. All of this leads to here let's actually add this all of this leads to a plummet in the innate immunity and that's when these patients become susceptible to infections. So the bacteria, if they're not getting killed because of being eaten or broken down, they can start causing tissue damage, alerting the immune system and causing an inflammatory reaction, really ramping up your cytoines. Here's another thing. When we think about this, the bacteria, they're normally coming, usually they're on like our skin, right? They have it a part of your your mucosal linings. What happens if you have something like for example you have a severe let's say cellulitis 9:04 or you have a surgical site a surgical wound that is maybe a little bit open maybe it's a little dehissed maybe it looks a little rough and these types of scenarios when a patient has things like cellulitis or a surgical wound you can have little bacteria here we'll represent in these green dots they're normally a part of our our skin flora and if you have an immune system guess what these bacteria, they try to jump in. Who's going to come and eat these suckers? The neutrfils. Do you got the neutrfils? No. What happens is they start to work their way through here and they get into the bloodstream. Same thing here. Uh when working in the ICU or patients who have cancer, guess what else they have? So ICUs, you see a lot of patients who have like central venus catheters, usually in the uh internal jugular vein, the subclavian vein, the femoral vein. That's all part of the skin. And there's usually a little tunnel when you dilate the skin. it can create like a little space where bacteria can kind of tunnel through there. Another thing is when you have indwelling catheterss that sit in for a long period of time, that's a potential source. So sometimes if there's a little 10:04 bit of space, maybe there's some bacteria that's on one of the caps, maybe there's some skin here that the bacteria kind of like tunnels and gets its way through. Either way, these things can get into your bloodstream. And if you had like an normal immune system for the most part, you'd probably be able to clear some of these. Either way, this is a risk. So, having indwelling catheterss, ah, it's a it's a terrifying things, especially on a patient who has neutropenia or some malignancy and just got hit with some chemo radiation. So, indwelling catheters is another big one. So, either way, let's say that a patient has an underlying malignancy such as let's just say for example, they have AML, they get chemo radiation, but then on top of that they have an indwelling catheter. They may get the chemo, drop their neutrfils, lose the ability to fight off infections. They have an indwelling catheter. The skin flora gets into the circulation. Boom. You have an opportunity for bacteria and not enough neutrfils capable of clearing that. That's when you're going to start seeing these issues. Either way, what I want you to remember is in these scenarios, 11:05 these bacteria are critical to know. So, usually skin and indwelling catheterss, these are really important to know that these are usually going to be your grandpositive bacteria. So these are going to be your Graham positive bacteria. So which one are those? That's your streptococcus. That's your staflacccus arius which is the one that we get really really terrified with though. The scary one. It can really wreak havoc. This is the scary one that I think we think about in patients because we don't want to miss is MRSA methasylan resistant staflauasarius. So we got bactaria this way. What's another way that you can get bacteria? Another one is you know what it's interesting whenever people get chemo radiation especially uh chemotherapy it can cause colitis. So it can cause that it can even hit some of the small bowel a little bit too but whenever you cause mucositis so there's a mucositis from chemo radiation therapy and then on top of that you create little holes now. So 12:05 now you have breakdowns. If you have mucositis you could potentially create little breakdown in the mucosa. So any kind of bacteria that's present in your GI flora, guess what? They're going to move right through there and they're going to get right into your bloodstream. Right? So having situations where a patient has colitis usually this is after. So it's secondary to that's what the two 2x two is secondary to chemo therapy. We see this a lot sometimes even radiation therapy. This is important because then it just causes a mucositis. You get a breakdown in this barrier and guess who can just come flying right out into the bloodstream? Your bacteria. It's important to know what kind of bacteria are part of your GI flora. Primarily gram negative rods. So this is going to be your gram negative bacteria. These are the the scary ones, right? They're they can be really really nasty. So gram negative bacteria. What are some examples of these? EC coli, klepsiella, right? Uh 13:08 you could have so many more. Shagella, you could go down the line, but there's really one scary one that we don't want to miss because it there's specific antibiotics and it's it can be a really nasty one and that's called pseudommonus particularly pseudamonus origiginosa. So we can have a colitis which is very common. So if you get chemotherapy, not only does it knock down your neutrfils, it causes mucositis. And this is not just in the git. This could be colitis. When I say git, I mean the actual small intestine, large intestine. Sometimes it can even be less in the oral cavity as well. So watch out for that too. I would even watch out. And when I say these, let's just actually be more general for the git. Let's say mucositis. Let's actually say muccoitis. And so that can include anything from the oral fernx, the esophagus, the stomach, the small intestine, and the large intestine. It just happens to be the colon is a pretty common one. All right, there's that one. Another thing is the urinary tract. This could be a 14:10 couple different things. Anytime you have foreign material that's present, what could this be? A Foley catheter. So, Foley catheters introduced opportunities because they can travel along the actual tissue, whether it's along the areas of the urethra for the male or the female. It can travel its way up sometimes and get into that actual urine stream right here into the bladder. What's another one? Let's say I got a stone or some type of obstruction here. The bacteria will back up and it'll build up here and then what will happen is it'll then move into your circulation. So in patients who have a foley catheter which is introducing foreign material or an obstruction. So let's say a urinary tract obstruction. And you know what? It's funny. When I worked in the ICU, 15:12 one of the primary problems I never thought that Foley catheters truly caused as much of we see of the catheter associated tract infections as long as they were patent and they were being switched out after a certain amount of time. I found they were have a kinkedked Foley. That was actually more problematic because then you can't drain it and then it backs up and then it moves its way backwards and then that gets into the kidney. That kidney then spills that into the bloodstream and then that's how you get the actual bacteria into the bloodstream. So I found that usually kinkedked foli catheters and urinary tract obstructions create an opportunity for bacteria to get in and again usually you should have an immune system to kind of clear this but if you have neutropenia it's going to be very very fast and accelerated. The last one is usually some type of breakdown in your um your lung tissue. So these are patients who are definitely a little bit more predisposed than risk. You have normal bacteria part of your flora here, part of your respiratory flora. But if you have that drop down in the neutrfils, then it's going to be an easier opportunity for some of these 16:10 bacteras to kind of seed into the bloodstream. So these are the things I really want you guys to remember is when we talk about patients who have the bacterial source a lot of the times really look at the skin look at surgical sight wounds think about indwelling catheters. If they got chemo radiation therapy think about mucositis look for sores or lesions in the mouth and the fernx and think about do they have any abdominal pain diarrhea. It could be that they have some colitis as well. Do they have any history of dyseria, flank pain? That could be something. Consider your analysis. And do they have any potential symptoms of respiratory distress? Oftentimes with neutropenic fever, they don't produce a lot of localizing signs and symptoms. That's what makes it challenging because generally neutrfils are guess what they're supposed to do? Amp up your immune response. So you don't see a lot of those localizing signs and symptoms. Usually what happens is they get very very sick and they become septic. So now that we've talked about this, we got a patient who got chemo radiation. and they have probably some underlying hematic malignancy that puts them at 17:08 risk of neutropenia. Chemraiation shut it down more. They don't have the immune response to clear the bacteria if they're present. Instead, because of the bacteria, they're really creating a cytoine storm, but it's not creating the best localizing signs and symptoms. It's usually more systemic infection symptoms or SERS and septic- like symptoms sources skin and dwelling catheterss for gramositive bacteria. The mucositis is the really important one for the gram negative bacteria especially from some part of the colon the small intestine or some oral cavity fingial areas. Now that we've gotten that and we've gotten the two big scary bacteras that can have a lot of mortality on these patients what would be a way that they would present? Well, we kind of talked about it if you have these bacteria. So here I'm going to represent this as your gram negative bacteria. I'm going to represent this as your you know your strep caucus which is your grandpositive bacteria. I'll represent this as kind of like your cluster. So this is going to be another your stafloccus your grandpositive bacteria. You don't have that immune system to really help you right. So what 18:10 are they doing? They're producing that unfortunate toxin mediated destruction of tissue cells. And I told you that these tissue cells respond by alerting other areas. you know, maybe telling macrofasages, other immune system cells, hey bro, I need some help. And so they secrete these different types of cytoines. Even the endothelial cells do this a lot too. And this is usually interlucan one, interlucan 6, tum necrotic factor alpha. These are really pumped up. And the problem with these is that they have a lot of different targets. And I find this is, you know, the interlucan 6 plays a pretty big role in this. But what happens is is that these love your hypothalamus and they're going to go to the hypothalamus and they're going to stimulate the hypothalamus and they're going to type the hypothalamus, hey bro, there's a there's a lot of inflammation going on. Can you rev up the body's kind of like internal body temperature? Make it a little bit harder for some of these bacteria to survive. When it does that, it increases your body temperature. 19:13 All right? It does that in multiple different ways which we're not going to go into but obviously view through you know changes in vasoc constriction is one of the big ones and so it's going to definitely increase the body temperature and it's going to do it to a point where the patient starts to exhibit a fever. Now how do we define a fever? Well, a fever in these patients is usually greater than 38 degrees Celsius. Whether that is a um usually in this potential scenario is if they have a fever is we look for this to be kind of consistent. Um so they've had a fever for maybe at least two days. But another thing is is that we can have a one time. So like if let's say that you have a one-time temperature where it's like 101° F. In that scenario, we actually could say that that's considered also a fever. And even if it's one reading, that's something especially if the patient has neutropenia. So fever is a really scary one. So when you have a patient who has 20:14 a fever greater than 38 degrees Celsius plus neutropenia, absolute neutrfil count less than 500 cells per microl, you got neutropenic fever, right? The scary thing that we truly get worried about with this disease is that sometimes it can be kind of silent. And what will happen is is that they'll act on the vessels. All right. So, they have little receptors on different capillaries, I'm sorry, arterials. And so, let's say here I have an arterial and I got some receptors for it. When these chemicals hit these receptors, it can trigger two things. One is vasoddilation. All right? So, it makes the vessels bigger, more a larger diameter within the lumen. And the other thing is it makes the the capillaries super leaky. So, you know, it's easier for things to leak out. And the whole point of that is that if you have an inflammatory response like let's say in this area, you want this vessel to be leaky so that white blood cells can get into the area and fight off whatever it is that's going on. So it's going to have a increased vasodilation and increased capillary permeability in 21:16 these vessels. And the problem with that is is that what this will do is is this will cause like a drop in your systemic vascular resistance and it'll drop your blood volume, right? Your effective arterial blood volume. So your systemic vascular resistance will go down and your blood volume will go down, right? Because now you have less resistance because the the larger the diameter, the less resistance to flow. The combination of these is we know blood volume and blood pressure are very you know cons you know very I'd say directly proportional and so if there's a drop in blood volume there is a drop in blood pressure and whenever systemic vascular resistance goes down so does your blood pressure and so what we start to see is that patients can start to experience a drop in blood pressure and so this may kind of rear its ugly head in the form of hypotension right and so that's where we kind of get a a little scared. Could this be a patient who's starting to exhibit signs of shock? And then this is 22:17 a very specific type of shock. Right? So whenever I have a patient who we have, we could define something which we can say is sepsis. There's a lot of different criteria out there. But I'd say this criteria is really kind of concerning. If I have a fever, if I have a decreased number of my neutrfils, which is going to kind of overall it's going to drop my number of white blood cells, right? And if I have a fever and if I have bacteria, if I have bacteria, I have positive blood cultures. So I test, I actually test their blood and I test it for bacteria. If it comes back with bacteria then we technically have sepsis my friends. It's when we get into the combination of hypotension that is when we start getting concerned of has it progressed to shock. And so sometimes patients may come in with a 23:17 fever, a neutropenia, and a bacteria. But then they can get sicker and sicker and sicker and then eventually progress to shock. And this is where we get worried. Let me actually kind of redefine this one. Let's redefine this as septic septic shock. So that's what I want you guys to take away from neutropenic fever. So taking away from neutropenic fever is a patient who usually has an underlying hematologic malignancy where they already have a slightly lower neutrfil count get hit with chemo radiation shut down the bone marrow more suppression and neutrfil production that drops can't clear infections as well because of an innate immunity decrease because of that bacteria that are getting their way into the bloodstream via this different ways can then thrive and cause tissue damage. This tissue damage sometimes doesn't cause a lot of localizing signs and symptoms. It may cause a fever but sometimes it can get progressive enough that this patient can go to get develop sepsis and then sometimes precipitously and I mean quickly develop septic shock. 24:18 So really important to identify that with nutriin fever. We talked a lot about this. We see this primarily in a patient who has some underlying malignancy. Usually it's a leukemia of some sort. That's really the big one. Um and what happens is is usually they have some type of malignancy and they're getting hit with chemotherapy as well. And when you get hit with chemotherapy, what happens as a result of that is that you cause milo suppression, especially even radiation therapy. So you suppress their bone marrow from producing neutrfils. And if they have some type of like hematic malignancy like leukemia that already is producing less functional white blood cells, that's going to create an opportunity where they just don't have the immune system to fight off infections. And plus, when you get chemo radiation therapy, it breaks down that mucosal lining and it allows bacteria to transllocate. they get into the bloodstream, you get bacteria, you run the risk of infection because you just don't got the immune system to fight it off. And so I see this a lot in patients with sepsis. So patients who come in septic and we start working them up and we end up finding 25:16 that they have neutropenia and they also have an underlying malignancy. They just got chemotherapy recently. That's a potential source of that sepsis. But again, I really want you to think about this more in the vignettes as a patient who comes in with a new onset fever who has a history of malignancy, more likely kind of a hematologic one and they've gotten chemotherapy. So, they're suppressing their immune system, destroying the bone marrow that's causing myo suppression. They may already have a reduced functional white blood cells in the first place. Now creates an opportunity bacteria transllocate. They get into the bloodstream and that's when they get the fever. What's a fever? Usually greater than 38 centiggrade. So now you got a patient with a fever. You got a patient with sepsis. They have a history of malignancy. They have a way of having that mucositis or breakdown and a barrier that allows for bacterial transllocation. How do you prove that the white blood cells are low? You get a CBC with a diff. That's going to tell you if the white blood cell count's low. And the differential is going to tell you which one of the white blood cells, 26:09 the neutrfils. But what I really want is that absolute neutrfil count. If that's less than 500 cells per microl, we have a diagnosis of fever plus neutropenia. We got neutropenic fever. The question here then becomes, what do I do next? At this point, you really have diagnosed. You don't have to go further. I think if you're ever asked, well, what do you do once you've diagnosed the patient with neutropeni fever? Well, the most likely thing is you'll start them on broadspectctrum antibiotics. But once you start them on broadspectrum antibiotics, you can't keep them on that forever. You know, you may keep them on it for like, you know, maybe a week or two or something like that. Usually at some point though, we would like to narrow down antibiotics to to be more specifically geared towards that pathogen. And that's where blood cultures are going to come into play. You're going to start them on antibiotics once you diagnose it. After they get their after they've, you know, you've done that, you order the antibiotics, they're getting ready to come, you quick get blood cultures. You do the blood cultures, and you order cultures from other areas or sites 27:09 depending upon their symptoms, but blood cultures is going to be the first one. Another one I like to do is a chest X-ray right off the get-go. So, I like to get a chest X-ray to see if they have any kind of diffused pulmonary infiltrates because that's a very common area as well. So, some kind of pneumonia, bacteria can easily spread across. So, I like to do blood cultures and I like to do a chest X-ray right off the get-go. And if I see these things, I'm pretty concerned. Now, I think the really really important thing here is you want to try and figure out, do I order further tests? You only do that if they have specific signs and symptoms to point to that area. So for example, if they have cellulitis, an abscess, a big surgical wound that looks gnarly, wound culture it. If they have, you know, a urinalysis that's very abnormal with pyura, lucasite eststerase and nitrates that are positive, they have dysura frequency, urgency, get a urine culture. Right? If they're if they've been a long-term chronic catheter uh patient, get a urine culture potentially. Um I think those are really really important to consider. Um, if they have abdominal pain, severe diarrhea, I would consider 28:11 getting a stool culture. Um, I would also get a sputum culture if they have any kinds of respiratory symptoms and their chest X-ray came back abnormal to. The whole purpose of this is that once I get my blood cultures, that'll tell me their bacteria. But then I also can get other cultures to find out where is this potential source coming from. Because maybe it's not in the blood yet. Maybe their blood cultures come back negative, but they have another source in their body. And so these are always kind of things to consider because it helps you to tailor your antibiotics towards the specific pathogen because we'll start them on venkcomy to cover MRSA. We'll start them on piper tasobactum or sephopim to cover your pseudonus and a lot of your other gram negative rods. But once we've done that, that's the broadest spectrum. At some point, we want to narrow it down to the specific pathogen and that's what the cultures are going to help us with. Bulb cultures are going to be the main one. These other ones you can do based if they have symptoms and signs. But either way, this is really the the way of determining their sepsis and infection. How all of these patients will likely most often 29:10 present which is a fever or a septic patient with a known malignancy and they've gotten some type of chemiation therapy that broke down a barrier that allowed for transllocation. So you've gone through you have a patient who has neutropenic fever, right? We talked about how they probably have a hematological malignancies, they got chemotherapy, they now have a fever, they got an absolute nutrient count less than 500. What do you do? You ordered the blood cultures. You're waiting for those to come back. You maybe got other cultures depending upon localizing signs and symptoms. In the meantime, you have to put them on empiric antibiotics. This is going to be venkcomy most often to cover MRSA and then piper and tasoactum or sephop to cover your sudamonus and a lot of other gram negative rods. That's going to be what you're going to do until you get the cultures back which says what kind of bacteria you have and then you narrow down to what it's susceptible for. All right. So, let's talk about tumor lis syndrome. So tumor license syndrome is a really important oncologic emergency. What you really want to be thinking about with this one is that there's obviously it's it's 30:05 pretty easy. I mean it says within the name there is licis of tumor cells. And so I think that begs the question of okay we're obviously talking about oncology here. So what kind of tumor cells is popping is the question. And this is usually when we think about tumor lis syndrome, we see this in patients who have what's called ALLL. So acute lymphoblastic leukemia is a pretty common one. And another one is lymphoma. And there is different types of lymphoma. So if I were going to tell you which one, I would say things like non-hodkins lymphoma, things like burket, things like you know diffuse large bell lymphoma. Those are going to be the more likely ones. So if a patient has all lymphoma, they have a pretty heavy let's say tumor burden. So they have an increased tumor burden, they already got some heavy heavy amounts of tumor cells that are constantly, you know, going through their their replication cycles. So if you have a lot 31:07 of tumorous cells and you hit them with chemo, so then let's say that you give them a pretty good dose of chemotherapy. What's that chemotherapy going to do to these cells? Well, we already know. I I got to point it right at them. It's going to pop these dudes, right? And so now we bust open these cells. When you bust open these cells, you release their intracellular contents. One of the really important ones is going to be phosphate. All right. So phosphate is going to be one of these that'll go up. All right. The next one is uric acid. So we'll write here uric acid and this is just because of a lot of the DNA processes that are going on right a lot of the nucleotide metabolism from whenever you have a lot of cell replication right so a bump in the uric acid would be a pretty scary one and then the last one is what is the most abundant extracellular cation that's pres I'm sorry what is the most abundant 32:09 intracellular cation that we have that's going to be potassium we're just bags of potassium, these these cells of ours, right? So, these are going to be the primary things that leak out of these busted open cells once they get released. Things like phosphate, you know, it's it's one of these that'll actually bind with calcium. So, what it does, it binds the calcium. And when you bind up calcium because that basically it kind of causes like a a chelation mechanism essentially you're going to do what to the free ionized calcium levels? You're going to drop them because now it's bound to phosphate, right? So now you're going to drop what you're calling your ionized or your true like free calcium. So we'll put this as your ionized calcium, right? So you can start to see patients having hyperphospatia with hypocalcemia. The other thing is that uric acid, this is this is pretty nephrotoxic. It actually crystallizes. 33:09 And so what happens is it'll actually kind of get into your nephrons. And when it gets into the nephrons, it causes a lot of nasty damage to your proximal tubular cells. And if you don't actually get enough of this filtered out, but you have a good amount of uric acid crystals, it causes uric acid neuropathy. And uric acid neuropathy usually presents in the form of an acute kidney injury. Um and the most common type is acute tubular necrosis which is an intrarenal AKI. And then the last thing is the potassium we know that it is super critical to our cardiac activity. Obviously it plays a role in our depol repolarization mechanisms and so what happens is it changes a lot of that and so these patients become very very high risk for cardiac arhythmias. So arhythmias is a big one but I think when we talk about arhythmias obviously the scariest thing is that these patients can develop things like well VTAC vib pea arrest um so that's kind of our scary things that we actually get 34:09 concerned about sometimes obviously asy is another one but another thing that we'll talk about with arhythmias is that they can really be something that we can pick up on the exam with EKG changes so we will talk about that so big thing that I want you guys to remember here is when a patient has tumor lis syndrome they have to have a heavy tumor burden and it's usually like a hematlogic malignancy such as all lymphoma. They get chemo, bust them open, release these things and they start to cause a lot of different downstream consequences. So, let's talk about that because I think that will kind of like really hammer down the point of what's going to happen with the high phosphate. Well, we kind of know, right? These cells pop open. What was that first one that I told you about? It was the phosphate, right? So, we got a lot of phosphate. Now phosphate, one of the things about this is that we already talked about it. It's going to lower the ionized calcium. So it'll bind with the calcium and whenever it binds with calcium, it lowers the true ionized version of calcium. So now you got low calcium. The problem is when you have lower amounts of ionized calcium, calcium is 35:12 very peculiar. And what happens is is it is it kind of controls your voltage gated sodium channels. So imagine calcium is if calcium is really high, it can block some of the sodium because it competes with it to a degree and so it can block that sodium because it can repel the sodium from actually moving into these channels. But if you have less calcium, are you going to have as much of that repelling it and competing with the sodium there at that channel? No. So what happens to the activity of that sodium channel? It goes up. And so what happens is you get more sodium, you get an increase in sodium influx and these voltage gated sodium channels. So more sodium is going to be pumping into these neurons. This is a neuron, right? So you're going to have a we'll use a positive symbol here, positive symbol here, positive symbol here. These things are rushing. Not rushing, you know, like you know, like Russian vodka. No, this is rushing into the neuron causing it to 36:13 depolarize. When it depolarizes, it sends signals down and increases action potentials. Bro, when we get more action potentials in these nerves, the problem with this is is this leads to a lot of neuromuscular irritability. That's a heck of a word, right? So, it's going to lead to a lot of things called neuromuscular irritability. Let's write that down. Neuromuscular irritability. All right. So, what are these people just like mad at life? No. No. No. There's specific clinical symptoms that can sometimes be seen. For example, one, and this is, I think, a classic one that you see on the exams because it's just easy to kind of like talk about, it's peroral paristhesia. So, you get kind of like some numbness and some tingling around the oral area. The other one is it can lead to what's called shavesteck sign. Shavesteck sign. What the heck is shavesteck sign? Shavesteck sign 37:16 is basically when you have facial nerve irritation. You take and you tap over where the facial because the facial nerve run kind of runs right here through that parotted. you tap around that area and then they get kind of contraction of that facial uh muscles because the facial nerve is getting activated and so it's changing the muscles of the facial expression. They're getting all you know yanked up right there. That's one sign. So a positive scheme. Another one is a positive tresos sign a positive trusso sign. And this is when you inflate the blood pressure cuff over the brachial artery. There's a nerve there and you start to compress that nerve and then guess what happens? Some of the the nerves that run down obviously we'll kind of get to like that media nerve. It starts to kind of get compressed and then what happens is is you start to have flexion at the wrist and then the flexion of the actual fanges. So you get 38:16 what's called a carpedal spasm and that's usually as you inflate the blood blood pressure cuff off high enough it starts to compress on those nerves. You activate it and it's already kind of like a little sensitive. Boom. You know, so it's like you got sensitive nerves and you're trying to trying to mess with them. The I think the biggest thing and I would say it's not common but that's what I'd be scared of is that in worst case scenarios this can cause seizures. All right, I haven't seen it but it's something that I would say that would be considered the emergency aspect. All right, the next one is you are pumping out that uric acid. Now the uric acid is where I think a lot of the problems u lie in tumor lis syndrome that and and I think the the um the potassium but I think uric acid can can contribute to that as well interestingly enough. So the uric acid, what happens is is that this is um it's pretty nasty, man. And basically what it happens is is it can cause um uric acid crystals. So let's actually just kind of represent these here. Let's do it like this. Let's say here we got like a little bit of you 39:17 know uric acid crystals that you get here. So here's our uric acid crystals. This kind of moves across the glomemeulus, gets into the proximal tubules, right? And then what it does is is it actually gets into these proximal tubular cells. And when it gets into the proximal tubular cells here, I'll do it like this. Kind of like that. It gets into these cells and it causes damage. The cells aren't a great fan of it. It can actually cause nephrotoxicity and then these cells start dying. As these cells start dying, they sloth off. So now let's imagine here's the damaged cells. Here's the damaged cells. These are all damaged. What are they going to do? They start to sloth off. So now, let's imagine I got a bunch of these cells that sloth off. Because I'm only showing a couple, but there's obviously thousands upon thousands of cells here. They start kind of clumping. And as they clump these cells, they form 40:19 a kind of like shape of the the proximal tubial cell, proximal tubular lumen. So these start kind of dumping here in. And what happens is they make what we would call a cast. So they make something called muddy brown casts. And the problem with these casts is is that they block the flow of urine moving down. And as they block that flow of urine over time, what that does is that drops the ability to filter things off from the glomemeilus. All right? So then you lose this ability. And as you lose this ability, what what happens if you can't filter things across the glomemeilus? That's called your GFR, right? So your GFR drops. If your GFR drops and you got these damaged cells, that's when you start seeing potential problems because these cells are damaged and now you can't secrete things and the GFR is lost. And so now you're having a hard time filtering things. So there's 41:19 decreased secretion because of these damaged cells. and there's a decrease in the GFR. Bruh, guess what this is going to lead to? If I can't secrete things like creatinine, potassium, uh, ura, water, all of these things. If I can't filter off potassium, ura, water, etc. This is where you're going to start to see AKIs. So, acute kidney injuries. And how do we truly define an acute kidney injury? How do we truly define if you had to define an AKI? How do you do it? It's an increase in the serum creatinine. Usually we say greater than 0.3 milligrams per DL within at least a 20 usually a 48 hour period. All right, that's how we would be concerned about this. So if I start seeing a really really sharp rise in the serum creatinine, I would be concerned about acute kidney injury. And if uric acid was elevated, that could be the potential cause. I got uric acid neuropathy. So that's where we get concerned is you know these uric acid 42:22 neuropathy. Here's the other thing is with with uric acid nephropathy when you get an acute kidney injury guess what else that happens if you get a severe enough one obviously we know the AEIOU right acidosis electrolyte abnormalities which is the electrolyte potassium. So a patient who gets tumoris syndrome they can cause AKIs. Guess what AKI can do? Increase potassium. What do they already have spilling out of these busted open cells? Potassium. And so if I have potassium that's rising because of the busted open cells and because of an acute kidney injury, I can't filter and secrete potassium as well primarily filter it though. What is going to be the issue here? we get an exacerbated effect here and that's going to cause this hypercalemia to worsen the cardiac arhythmias. So that's what we get scared about is acutely. When this potassium rises enough, you can get cardiac arcas. But if the AKI continues to progress and you still have this, you know, let's say concerning potassium, 43:23 but it's not life-threatening at the moment, this can worsen it. Problem with that is we already talked about it can cause cardiac arhythmia. So obviously we get worried about things like VTAC, we get worried about VIP, we get worried about PA or ascy, right? But the problem is is that often times, yeah, most patients will present this way and you'll have to proceed with CPR. But oftentimes we get these kind of like EKG changes that are worth talking about because this is sometimes how they'll talk about this on the exam because they want to figure out a way of how we can talk about this. So one of the first ways is that these patients will peak their T-waves. Then they'll prolong their PR interval. Then they'll lose their Pwave and then they'll widen out their QRS complex. Then they go into what's called a sine wave pattern and they can break down to VTAC VIB. They can go into a complete flatline. So, these are the things that we worry about is do they have a peaked T-wave? That's the first one. Do they have a prolonged PR interval? Do they have a 44:25 flat Pwave? Do they have a wide QRS complex? Are they presenting in a sinewave pattern? These are the things I want you guys to think about with this because this is what they'll try to test They'll say they have a patient who comes in has a history of all or non-hodkkins lymphoma got chemotherapy all of a sudden they have an EKG and it shows peak T- waves. What is potentially going on? They may have tumor licis syndrome and that's because of the potassium leaking out of the cells. All right. And then they could also say they have an acute kidney injury or there's a uric acid nephropathy. How is that contributing to it? Because an acute kidney injury loses the ability to filter off and excrete potassium now and that's you know accentuating the effect that they already have from the hypercalemia. So that's what I want you to take you guys through here with tumorlyis syndrome. All right, tumorlyis syndrome, al l lymphoma, big heavy tumor burden. You bust open the cells, release out which ones? Phosphorus, uric acid, potassium, and which one drops as a result of high phosphorus, calcium, neuromuscular 45:26 ability, AKI, and lastly cardiac arhythmias. All right, tumoris syndrome. We think about this in a patient who again has an underlying malignancy. I'd say the most common ones are going to be things like an acute leukemia of sorts, right? I'd say all is a really big one. Lymphoma is a really big one, especially your diffuse large B cell, your burket lymphoma, anything like that where they've gotten chemotherapy, right? And in this case, they're not coming with a fever. They're coming with most often things like an acute kidney injury. So if you hear that, you hear things like cardiac arhythmias or neuromuscular irritability, these may peak your thoughts to think about, ooh, could it be TLS? Well, how do I prove that? Well, the primary reason this happens is when you hit those cells, they bust open and they release things like phosphorus, uric acid, and potassium. The phosphorus chilates the calcium and so they end up with hypocalcemia that cause the neuromuscular irritability. The uric acid causes the acute kidney injury and the high potassium causes the arhythmias. Either way, in these patients, you want to think about that 46:27 if they have a new mal or they have a known malignancy and especially if they've gotten some kind of recent chemotherapy. Now, I'm gonna get a CMP because that's going to tell me my renal function, if they have an acute kidney injury, right? It's going to tell me my potassium will tell me my total calcium. I'm going to get my phosphorus to see if that's high. I'm going to get an ionized calcium if the total calcium comes back a little uh elevated. And I'm going to get a uric acid. All of these things are going to help me because what I need is I want to see PUK. I want to see phosphorus high, uric acid high, potassium high, and I want to see calcium low. That's what I want to see. So phosphorus is high, uric acid is high, potassium is high, and calcium is low. I have tumorlyis syndrome. And that's it. The diagnosis has been made. Again, this is more of a thing where you have to have a high degree of suspicion for this. Patient comes in, they got a nuance at AKI. That's not a a quick thing that you're like, oh, it's TLS. No, you have to go through, is it post-renal, is it prenal, is it intraral? oftentimes you'll start and you'll work them up. You know, you say, 47:23 "Let me get a bladder and a renal ultrasound. Make sure it's not post-renal. Let me look at their volume status to see if they're hypoalmic. Let me look at their medication history and go through that to see if they have any kind of drugs, insaids, if they're on some type of ACE inhibitor, if they're on an ARB, if they have some type of hypotension or shock. We go through all of these different things. We do phen. We do urine sodiums. We do urine microscopy to look for any kind of cast. All of those things come up. But once you've gotten to the patient who has a intrarenal AKI, this should be something to think about. When you have a patient who comes with arhythmias, you're thinking about you know potassium related changes, peak T- waves, flattening of the Pwave, prolonged PR interval, YQRS, sine wave, cardiac arrest, etc. Uh neuromuscular ability, you're thinking about this in the patient do a shave sex, tricose sign, peroral paristhesas, maybe worst case scenario, a new onset seizure. These are things I want you guys to be thinking about. So you have a patient comes in, they have some type of malignancy. Usually this is things like all lymphoma, they got chemo. Now all of a 48:22 sudden they come in with an AKI. They have cardiac arhythmias with you know T-wave changes. And you diagnose this. What do you do? Well, the big big thing here is that the things that will kill them is going to be most likely the arrhythmias um as well as the acute kidney injuries. But when you think about these patients, the big problem here is that a lot of the times you have to try and and do the best you can to treat the kidneys first. Because if you treat the kidneys, one of the benefits of that is that you reduce that risk of the further kidney injury and the more kidney injury that get you get, the more risk you'll need for dialysis, the more risk that they'll have of hypercalemia. And so you're really trying to go after that. So the first thing I like to do is I like to consider fluids. fluids for the patient who's maybe getting ready to get chemotherapy and they're high risk. They're already a high risk of getting tumorly lyis syndrome. I'll give them fluids. All right. Usually things like lactate to ringers, normal saline, one of those. All right. The other situation of when I would give IV fluids more likely a little bit more 49:22 volume is when they have an acute tumor license syndrome. We're not It's really I think a misconception when you give fluids to a patient with TLS. It's not because they're massively dehydrated. It's not because you're trying to flush these toxins or electrolytes out of their body. That's not really what you're doing. You're helping to maintain uvalia. You're helping to improve renal perfusion to the kidneys because in that scenario, you already have the uric acid crystals destroying the kidney tubules. And what you're trying to also do is let say, let me just give them enough volume where I don't further worsen their kidney injury. I want to keep renal profusion normal so I don't exacerbate their already present acute tubular necrosis and acute kidney injury. That's all you're trying to do. So you prevent a lot of this by keeping them volume resuscitated just kind of normal uvalia and acute tumor lysis syndrome. You're giving them again volume to just maintain uimmia. It's not for this theoretical flushing out of toxins. All right, that's really important to remember. The the thing I like to talk 50:23 about though in this scenarios is whenever a patient has tumor syndrome, you got to think about it. are busting open these cells. They got chemo. Pop. There comes things like nucleotides. These nucleotides get broken down eventually into uric acid. Uric acid is the nephrotoxic devil. This is the one that's going to cause those crystals. It's the one that's going to cause the acute tubular necrosis. All right. The next drug here is alopurol. And alipurol is kind of interesting because what it's going to do is it's going to act on this enzyme called zanthine oxidase. And zanthine oxidase is interesting because if you inhibit this enzyme, what you're going to do is you're going to inhibit the conversion of hypoanthine and zanthine into uric acid. And so you're going to get less uric acid, which means less nephrotoxicity. And so it's really good at decreasing uric acid before it's formed. And so that means it's not really good in the acute stages when uric acid is already formed in high amounts, right? You may reduce a little bit of it being formed, but once it's you have a massive amount of the spilling out of your cells, it's kind of too late. So this is more of a 51:16 preventative drug. Those who are high risk, I'd probably give this more in the prevention of tumor lysis syndrome plus the fluids, I would do this drug. If the patient has acute tumor lysis syndrome, it's already too late. These things are spilling out uric acid. Uric acid is already formed. Then what would I do? In that scenario, I'd use a drug called raspiricase. Raspberryase is kind of an enzyme where it's going to convert uric acid into allinone. Allen is not nephrotoxic. This is actually easy to urinate. Doesn't cause any destruction or injury to the kidneys. So now by converting uric acid into alenone, what happens to my uric acid levels? Drops. What happens to my nephrotoxicity? Drops. And so that's the beauty of this drug is it's really good in the acute tumor lis syndrome. So IV fluids in both conditions alipurol preventative raspirase more for the acute scenarios. All right. If a patient has things like hypercalemia we treat them the same way we treat hypercalemia. What do you do? Well first thing you got to do is you got to see okay let me give them some insulin to shuttle the potassium into the cells. Give them dextrose if they 52:17 have any hypoglycemia or they're near the range of normal glycemia. Um, on top of that, I would also think consider things like aluterol. That's going to help to shuttle the potassium into the cells. If they're acidotic, you can give them bicarb. But really, the key thing that you'll be doing in those scenarios is giving things like kioxilate to help excrete it through the feces or you give them things like ferosomi to pee that potassium out. And in worst case scenarios, you do dialysis. You're treating the patient who has hypercalemia the same way. If they have tumoris, again, tumoris is just the reason for their hypermia. And if they have instability of their cardiac membrane, so they have any kind of potassium related EKG changes, you give them calcium gluconate as well. All right. All right. So let's now talk about luccoasis. So again, you've probably noticed that we've talked about a lot of these oncologic emergencies in various different types of clinical lectures, right? So this should sound very familiar if you go back to our hematology lecture. We really talked about a lot of problems with neutropenic fever, especially with your acute leukemas. That's a really big one. We 53:14 talked about um tumor lysis syndrome a lot in non-hodkkins lymphoma. We talked about a lot in acute leukemias. And again you'll appreciate luccoasis again we talked about that in acute leukemas. So with that what is the one that we see it most often associated with? Well it's the one where you have just a massive and I mean a massive amount of white blood cells tons of luccoytes and that's usually we tend to see this we you can see this in all. So any acute leukemia, yes. But for your exam, I want you to try and me remember which one it's more associated with. And if you guys go back, we talked about one called AML, acute myoid leukemia. And so this one has tons and tons of these blast cells. And we know that blast cells, you know, there what's different about these is if you kind of go back to them, if you really remember, what were these things that were kind of on the side, the hour rods, right? So your myoblast with a lot of the hour rods. So here you're going to have a patient who has tons and tons of myoblasts 54:15 and it gets to the point where the number of myoblasts causes the total white blood cell count to be extremely high. Now we actually define this as hyperlucytosis. that bone marrow be pumping these things out to the point that whenever these get into the bloodstream and if we were to take a count of the number of white blood cells that are in your entire circulation here I'm just going to draw a bunch of different cells. Here's a bunch of different cells. You take a sample of their blood. What you're going to find is that their white blood cell count is going to be greater than 100,000. That's absolutely insane given that they should usually be somewhere from 4 to like 11 or 12, right? So, usually 4 to 11. So, we call this terminology wise hyper luccoytosis. I mean, this is just a astronomically high white blood cell count. But again, the proportion of it is being made up by the myoblast. Now, myoblast, they're 55:17 they're not mature. They're bigger. They also don't have a lot of the ability to kind of stretch and move and twist and get through small little capillaries. So, because they're larger, because they're less, I'd say they're more fragile and they're not as bendy, these are going to get stuck in a lot of your smaller vessels. So, they may be floating through this arterial fine, but as they get to your smaller kind of like vessels near the capillaries, they're going to start oluding. And as they start oluding, because what happens is when your white blood cell count goes up enough. You got to think about this. I mean, think about this pretty straightforward wise. When you got a white blood cell count that is so high, there's only so much in your vessel. Now, you're making less room for basic plasma. What happens to the viscosity of the blood? It goes up. So, whenever you have white blood cell count is this high, you can expect the viscosity to be through the roof. So now this patient will have a crazy high blood viscosity. 56:18 What's going to happen now to their blood flow? Oh, I'm telling you, it's going to suck. So they're going to have a reduced blood flow because of this increase in viscosity. And the problem with this is when that viscosity is high enough, it's going to start oluding the vessels. So then you start getting what's called microvascular occlusion, which is what we see here. Right? So now these vessels are all kinds of oluded. If that happens because it's by the white blood cells, what's going to happen to your oxygen delivery to the brain, the ability to drain uh venus blood out of the retina or oxygen delivery to the alvoli? It's going to suck. It's going to suck real bad. So now because of that, these patients start to experience organ eskeeia. And that organ eskemia will manifest in a couple different ways because it affects your central nervous system. It affects the retina and it affects your lungs. And so that's 57:18 what we get really really concerned about in this disease process is that if there's enough of these white blood cells that they're really really starting to cause this potential issue, we can see some scary scary symptoms. Dude, you can get patients and we'll talk about this a little bit later. They can have stroke like symptoms, right? Sometimes they may present mildly with like a little bit of a headache, maybe a little bit of confusion. So like a slight change in their mental status. They may come with just a slight bit of blurred vision. Sometimes they can actually have complete vision loss, sktoomas. They could have papa edema because of pressure being too high. They can maybe come in with a little bit of shortness of breath, but then they can come on fullblown respiratory distress, hypoxmia, chest x-ray with infiltrates, dude. It can be pretty bad. So that's why it's really important to remember that in patients who have AML, they're at risk for these lots of myoblasts, really really high amounts of them, that they really plug up the vasc vessels because of high viscosity from total amounts of big blasts obstructing those micro vessels and then you get organia. 58:17 So let's talk about what this would look like. So I told you it can block off vessels to the CNS. Let's imagine here, right? You take a second and you imagine here's a central nervous system, right? You obviously have a bunch of parts of the circle. Wells. If I olude off some of the MCA and it's usually the smaller ones. You're not going to olude off of a large vessel. You don't usually get that. You get, you know, more distally, you know, maybe an ACA, maybe a little bit distal down that one. Maybe kind of a more of a distal PCA, things like that. Because of that, you're going to cause decreased oxygen delivery to the brain. So, what that can look like is sometimes, yes, they can have things like a headache, right? You can have things like an altered mental status, but you can have, and I'm not kidding, you can develop stroke like symptoms. And I think that's where we get kind of like concerned. And that's when it starts getting to the point of where this is like severe symptoms because headache, yeah, it's it's it's not nice. It's not it's not great. Altered mental status not great. If you start developing stroke-l like symptoms where you're developing weakness, you're 59:17 developing sensory changes, that's when I would be concerned because that could potentially, it's not as common, but potentially you could cause a stroke if it goes along enough. Another thing you can also do is is sometimes these can even cause small amounts of hemorrhage. I've seen this where it can even cause small amounts of micro hemorrhages. So this is where I'd be concerned about its effect on the central nervous system is clotting off these small vessels where it starts off with headache, a little bit of a change in their mental status, but then it proceeds to stroke like symptoms and in worst case scenario they can develop a stroke. They can develop micro hemorrhages in the brain. Another one here, the lungs. Think about these guys clogging up the pulmonary arterials. So now you have less blood flow here going to get gas exchange. So now your gas exchange is impaired as a result where you're supposed to be allowing for oxygen to move here, CO2 to move here, and to leave out of this with 1:00:19 proper oxygenated red blood cells. No, you lead to decreased oxygenated red blood cells and this can precipitate in the form of hypoxmia. All right? And that's what we get concerned about is if you have a decrease in gas exchange here because you're kind of blocking off this process then you end up with less oxygenation and you end up causing hypoxmia. Problem with hypoxmia is that yes it may present mildly. So you may start off with just a little bit of dysnia but the problem is is that this can progress right you can get to the point where your respiratory rate goes up but you're breathing so fast and so deeply. So it can lead to things like typnia, right? So that's where I'd be a little bit concerned is has the patient kind of gone into the point of where they're typnic or they're breathing so fast and so hard that they're utilizing a lot of other muscles of uh respiration. So they're causing nasal flaring. There's a lot of paradoxical movement of the chest. Um their work of breathing. They're really really struggling. It's visible. Um that's 1:01:20 concerning, right? So that's what I'd be concerned about. Sometimes these can clog off enough of these like vessels where it sometimes can cause infiltrates on the chest X-ray. So that's another thing to definitely consider is it can cause chest X-ray infiltrates, but it's not super common. A lot of the times this is really a clinical diagnosis where you have a patient who has hyperlucasytosis as defined here and then other clinical symptoms. Usually it's neurological symptoms or pulmonary symptoms. And so this is what I'd be concerned about. Yes, I will write it down here. Sometimes sometimes you can get a chest X-ray um with infiltrates. I'd say that that is not as common as you would have written in the textbooks. The bigger thing is that they may have some degree of respiratory distress. Um and this is the ones that I get really really scary about is whenever their O2 saturation is really low. So, if they have a really decreased um SPO2, when you're reading that on their oxygen saturation, their respiratory rate is really high, their work or breathing is high, that's when I 1:02:21 get concerned about things like respiratory distress. And it's important to kind of like know the differences. And the reason why I tell you this is that in patients who kind of present with this, we need to escalate their therapy. If I got a patient who comes in with stroke-like symptoms and respiratory distress, I can start them on a drug called hydroxyora which will drop down their number of white blood cells, but it's going to take a little bit longer. I need something very very quick acting. It's going to rapidly drop their white blood cells and prevent this excessive neurological and pulmonary symptoms. That's where you use something called lucaperesa. So it is important to know the gambit of how they can present. All right, the last part coming down here is going to be the eyeball. So when we talk about this one with the retina um the biggest thing here is that whenever you have these u myo blast and they really can clot off these these vessels. We can see that it really can clog off the veins more so than the arteries because we talked about a lot of arteries here, right? So we talked about the cerebral vessels, we talked about the pulmonary vessels and these 1:03:21 are usually the arterial circulation. It's more often going to block off the retinal veins. So usually you'll get uh retinal vein olusion and when you olude off a retinal vein what that does is it causes vein engorgment and when the veins get engorged the problem with that is is that it can increase the pressure inside of these veins and then if you imagine let's say that there's the pressure is really really high because blood isn't getting out of here it can cause like little micro hemorrhages. So that's some things that can actually start to happen is you can start to get micro hemorrhages that can occur. That's one thing that I would be concerned about is is the patient developing micro hemorrhages. The other thing that we get concerned about is that obviously micro hemorrhages can cause things like visual changes, right? So they could experience things like visual changes as a result of that. Maybe some blurry vision, maybe some sktoomas can start to pop up. But another thing here is when you engorg these and especially if it's like let's 1:04:22 say that you have an occlusion a little bit more distal down here then you're going to get engorgment right here. And what that's going to do is is it's going to cause a lot of swelling here at the papilla. And so sometimes they can even get something called paplade edema. They get something called papal edema. And again, this also can cause some visual changes, but it's also something that's very easily picked up on fondoscopy. So, I watch out for that. Can you see this on fondoscopy? Because oftentimes what will happen is when you have a patient who has these presentations, you can get a fundos like maybe have a hyperlucytosis and you decide to do a fundoscopy on them and with the fundoscopy you end up picking up, oh okay, they got a lot of these like enlarged and engorged retinal veins and then they have some micro hemorrhages and they have papal edema. This is the one that is easier to talk about on the exam, but do realize you 1:05:22 can pick this up as well on phonoscopy. All right. So, luccoasis, what I really want you to remember is white blood cell count greater than 100,000 high viscosity clogs off the small vessels. Which ones? Brain, lungs, and retina. With that, you can have a gambit of presentation. depending upon that presentation determines if you do therapy that's I got time or if I ooh lucaparesis they need immediate rapid reduction in their white blood cell count luccoasis this is really a clinical diagnosis so this is when that white count is like super high greater than 100 so I'll need a CBC to prove that but how will I even think about this it's a patient who has a no malignancy it's usually AML that's going to be a really really common one that I would definitely want you guys to think about AML but it's a patient who comes in who probably has three systems that are being affected at least one of those three. Neurological because you get a lot of those white blood cells, they get stuck in the capillaries, the micro vessels of the brain. Um, or pulmonary symptoms because they get stuck in the pulmonary vessels or visual disturbances. They get stuck in the retinal veins. And if that happens, you 1:06:24 could have a patient come in with these neurological, pulmonary, visual disturbances, plus they have known AML. All I need is to really say, is the white count greater than 100,000? So, let me get a CBC. Let me get a diff. And that's going to be helpful. The peripheral blood smear is just a little extra step that you can add to see is there a lot of these blasts present and are there hour rods if you really want to go that length to prove that you may have an AML. So if the white count is greater than 100,000 we got hyperlucytosis. If we look at the differential and we see that there's a lot of blast there's a significant left shift that's helpful. And then lastly if I get that peripheral blood smear it shows that the blasts are not lymphoblast instead they're myoblast and you see our rod. So here's an example of some myoblast here. And if you kind of zoom in a little bit, you can see there's an hour rod right there. That's really suggestive of AML. And in this clinical scenario that I see right here, that's almost likely luccoasis. But we could go a little bit further if we really wanted to have extra test to prove that there's like these organs that are being damaged or injured. I 1:07:22 could do a chest X-ray to see if there's any pulmonary infiltrates. I could do a fundoscopy to see if there's any kind of what retinal vein engorgment. if there's any micro hemorrhages, papadeema, a neurological exam would really be the best to see if there's any neurode deficits. Is there alterations in their overall mental status? These are things that we could do, but you could even get a brain MRI and look to see if there's any small strokes or micro hemorrhages. But a lot of the times it's just clinical plus the known hyperlucytosis in the history that would bring about that suspicion. But if you find these things, all it does that really helps you. So again, you get that chest X-ray with the infiltrates, you get the fondoscopy, and you see something like a hyper viscosity retinopathy. Here's that dilated retinal vein. You can kind of appreciate right there. And you got some micro hemorrhages around the place. These are really kind of telling me that I got a hyper viscosity retinopathy. And again, a neurological exam that's kind of altered mental status when you did a mini mental exam. Um, and then you have maybe some neurological deficits like a 1:08:20 focal deficit. This could suggest maybe some potential stroke like symptoms as well. And again, you may go further and say, "Hey, let me get an MRI and see if I have any kind of like large vessel occlusion. Let me make sure that I don't have any kind of well large hemispheric stroke." The CTA would be for the large vessel occlusion, but you're looking to see if there's any likely cause of that. So, is there a stroke in that potential area? In this scenario, again, you have to have a high degree of suspicion, and that's why it's more of a clinical diagnosis. In this scenario, we got that white count that's through the roof, man. Greater than 100,000. I got to get that thing down. Well, there's two ways. One is it's really good. it just takes some time. And that's hydroxyiora. And so this is going to be for the ones where we have the time. They're maybe asymptomatic or they're they're not they don't have severe symptoms. They're not full-on presenting with stroke-like symptoms. They're not in hypoxia, respiratory distress. I got some time. I can do hydroxyiora right alone. And the patient who has severe hypoxia, respiratory distress, visual disturbances beyond belief, they're 1:09:17 almost blind and they have neurological deficits. They got stroke like symptoms. I can't just only do hydroxyiora. I can get hydroxyiora started, but I need to reach out somewhere in the hospital or a facility that does luccoeresis. Lucapharesis is going to be the go-to and severe symptomatic luccoasis because we got to drop the white count rapidly. This does it very rapidly and quickly. This one takes a little bit of time, but they're just about as effective as one another. It just is about which one in rapidity is required. So lucaperesis what you do is you remove the blood from the patient. This is going to contain the red cells, their white cells, their platelets, their everything. And what you're going to do is you're going to centrouge that into their separate layers. Once you do that, you get your red cells. You get your buffy coat which has your platelets, your white cells, you get your plasma. At that point, now what I need to do is I need to start separating out what? Separating out my white blood cells. I'm going to remove these white blood cells and then send back the red cell layer, the buffy coat with the platelets, the plasma back into 1:10:19 the patient. All I'm doing is I'm getting rid of some of the white blood cells. I'm decreasing their white blood count quickly and that's going to reduce some of the luccoasis symptoms. So again, the asymptomatic less severe hydroxyiora and the severe still give hydroxyora, but you also need to do lucopheresis to rapidly drop it and then you continue hydroxyiora after SVC syndrome. Uh when we talk about this one, I think this is again something we talked about more in like the lymphoma lecture. We talked about this also in our encology. Um and we talked about this particularly with I'd say lung cancer. You know when we think about lung cancer, yeah, swam cell carcinoma can but I'd say the more rapid developing one usually it's again more central. Two of the central ones is going to be squamus and small cell but you'll see it much more often given the rapid development the rapidity of small cell lung cancer. That's the one I'd be concerned about because that's nearby. It's near that kind of like central portion where it can compress on the superior vennea. So let's be concerned about that when we think about it. Lung cancer. Yes, we can talk about that one. 1:11:18 But the real big one, the concerning one is small cell lung cancer. All right. So with this one, I think what we get concerned about with this one is that again it can get pretty darn big and with that it can mush. What's this? Here's your internal jugular vein. Here's your subclavian vein. and they're going to join to make uh eventually they make the brachioalics and the brachiophalics combine. I'm just bringing it right here. I'm gonna say that this is the superior vennea. Look at this. We're mushing it. We're mushing this thing right here. That's one area where we can mash on it. All right. The next thing is also lymph nodes. We can get some big lymph nodes, right? Uh especially within the mediainum. Now, lymphoma, you have non-hodkins and hodgekkins lymphoma. And yes, Hodkins lymphoma definitely causes mediainal lymphatinopathy, right? With nodular sclerosis as these usually underlying subtype, but non-hodkkins is very aggressive, has tons of extra nodal involvement. But the concern with this one is when it hits those media lymph nodes, it grows rapidly. They really, really enlarge. So I'd say that you 1:12:19 would see this more commonly with non-hodgkins lymphoma, especially things like diffuse large bell lymphoma, burkets lymphoma. These are the ones that can definitely get pretty decent sized lymph nodes and compress. Again, yes, it's internal jugular subclavian and that goes brachioalic. But imagine there's another brachioalic coming here and then making the superior vennea. So, we're just kind of like going there. Look at this. Look at this dude. This is mashed to bits. So, because it is super super like small lumen, it's really hard for blood to move down the superior vennea. And so, what ends up happening is you get a restriction and flow. And so when there is a restriction in flow here and a restriction in flow here, that's where you get these potential issues. And so now I'm going to have a harder time for blood filling in to the right atrium and filling into the right ventricle. So there is a significantly reduced flow coming down from the superior vennea into the right side of the heart. And again, it's all because of right here. Look, just just look. I mean, I'm going to write it down, but look, look at that. Look how small that is. So you're 1:13:20 definitely going to get a lot of let's say um extrinsic compression of the S of the SVC and this is going to decrease the lumen diameter. All right, that's going to lead to an increase in the luminar diameter. So you're going to extrinsically compress the SVC and that is going to result in a decrease in lumen. That thing is tiny. And as a result, you'll get decreased flow into the right side of the heart. But because of this, you're going to get increased back flow. And what we'll talk about a little bit later is you'll get increased back flow into two potential vessels. And it's pretty easy to think about this guys. Come on. What when we got the brachioalix superva, what is feeding into the brachial phalics? Internal jugular subclavian. So what you're going to get is you're going to get a lot of backflow in the internal jugular. put I JV backflow and then you're going to get a lot of backflow into the subclavian veins and 1:14:21 so we're going to put that as SCV backflow. You're probably like okay what's the big deal about this? Well, there is a big deal about this and the reason why is this really comes down to this the internal jugular vein backflow. It's really really problematic and that's what I want you guys to really understand is what really constitutes an oncologic emergency because I'd say for the most part SVC syndrome is more of an urgency unless you get the rare scenarios of where we'll talk about this. You have emergent symptoms like increased ICP and respiratory distress. So extrinsic compression of the SVC from what structures? Mediosal lymph nodes or central lung tumors small cell lung lung cancer and non-hodkins lymphoma. Okay, when we think about this, let's say again, all right, if we really wanted to be anatomically correct, let's let's be anatomically correct because I don't want please don't like, you know, end me, but yes, there's internal jugular vein, subclavian vein, brachiophalic, and then brachioyphalic. Technically, you have the right and left and then you get this portion of the super vennea. So, at this portion here, 1:15:22 we have compression. So, let's actually kind of show this here. Let's say at this portion, whoop, I have compression. And then what's really compressing it? We can use those two different tumors. One, I'll do half of it is the lung cancer. Right? Here's the lung cancer that's compressing one. And the other one is the medial lymph node. And we'll kind of do this as the other half. This is accounting for the other half. And this is mashing there. Okay. Well, blood is having a hard time moving right through this thing. And then here, right? So as a result this is going to be reduced reduction here reduction here reduction here. So what ends up happening is is blood that is supposed to be flowing here ends up flowing backwards. Blood that's flowing here ends up flowing backwards and that's where we get the backflow problems. So here we'll start off with the subclavian one because this one is actually pretty easy. So you have increased subclavian vein backflow. What does a subclavian 1:16:23 vein get blood from? because this is all Venus structures, right? So, this is getting blood from your upper extremity and parts of your chest. And so, end up happening is all of these veins and I'm not going to draw all of them, but you know, all of these veins, they start to get kind of enlarged and then fluid starts to leak out of them. And as some of that fluid starts leaking out because of that increase in hydrostatic pressure, you start getting swelling and edema and distension of these veins. And so, that's where you start having some problems. You get upper extremity edema and you get chest edema and you get distended upper extremity veins. So that's one way from the subclavian vein backflow, right? All of these things are just going to get plumper. Hydrostatic pressure is going to lead to these things kind of leaking fluid out into the interstial spaces. You get some 1:17:24 swelling of the upper extremity, the the chest, and then you get some veins that might pop a little bit more from the J. This is the one that's that's really terrifying, right? So internal jugular vein backflow. So now we got a problem with this bad boy. So this one is backflowing. Well, with the internal jugular vein, when this one backflows, you got to think back to it. Remember, um a little bit of your anatomy, right? We got all these different types of cerebral veins. So you have your cerebral and technically they're cerebral venus sinuses basically they drain the brain parankma and then what they do is is they drain into eventually the internal jugular vein right these all are supposed to drain into the IG but if you have backflow are you going to have proper drainage age. No. And so 1:18:25 what ends up happening is that these cerebral veins, they don't drain. And as a result, there's a couple things that can happen. Obviously, they're going to get big. But anytime there's stasis of blood flow, you've run the risk of cerebral venus sinus thrombosis. But I think the biggest thing is what's the term called whenever the skull is a fixed space and you increase one of three things? brain, cerebral spinal fluid or blood. Well, if I start increasing the amount of blood, then I'm going to start causing an increase in the intraraanial pressure. So what ends up happening as a result of this is you get a increased blood um in the skull and that violates the Monro Kelly doctrine because we're not supposed to have more blood, more brain or more cerebral spinal fluid and as a result 1:19:25 what happens the intraranial pressure can go up. Now I have worked with a lot of neurological patients um a lot of neurocritically ill ones and I think one of the things that we talk about a lot of the time is that this would be relatively hard to do in general with a person who doesn't have already a brain substrate they have a bleed they have obstructive hydrophilis they have a mass they have something else that's already increasing their ICP a little bit what we always try to do is and This is something that is relatively I think controversial and try to teach about is we obviously try to not impede jugular venus drainage. So that's why patients who have neurological injuries we try to if they have high ICP already we avoid canulating the internal jugular vein for central venus catheters and we prefer subclavian vein because we won't thrombose or decrease the diameter of the internal jugular vein. So that's the concept here is patients who have superior vennea syndrome, you're kind of 1:20:27 decreasing the diameter. If they already have high introanial pressure and you knock off their drainage even more, ICP can go up. This can happen if you got a really severe enough obstruction though, you can cause an ICP crisis. That right there is what determines this to be a true emergency. Another thing is, and we think about this is uh internal jugular vein. it has. So let's imagine here we had the the jugular vein, internal jugular vein. It gives off little branches that can supply the larynx. Now if your jugular vein is distended, it's getting real real enlarged because the blood is just not being able to drain through it. It's little branches are going to get enlarged as well. And so these branches that supply the larynx are going to be problematic. So you're going to get a um increase increased luringial edema. All right? Because you're going to get a lot of fluid that's going to sit here and that's going to start leading to a lot of edema because it's going to again 1:21:29 hydrostatic pressure fluid is going to start leaking out into the surrounding tissues. And so you're going to get what's called lingial edema. And the problem with that is is that's going to narrow as you start causing swelling around the larynx, you're going to narrow the lingial inlet. that can lead to respiratory distress. And obviously one of the ways that we would be concerned about this is if a patient came in and they got strider that's one way because it's inspiratory strider air coming in there's a narrow lumen now or they have hypoxia right so these are the ways that we get kind of scared and concerned when it comes to um SVC syndrome is strider or respiratory distress presenting with hypoxia increased respiratory rate uh work of breathing is going up these are all concerning features so and back flow. Think about cerebravenous drainage is impeded. Think about backflow and increased hydrostatic pressure. So fluid leaking out into larynx causing lingial edema. The last thing is is most of 1:22:29 these you guys think about this this internal jugular vein right is going to run up. But another thing is that you know you're going to have some other problems where you're going to start causing some swelling of the neck and you're also going to get some branches here as well which are going to cause some swelling of the face. And so you're going to start seeing some jugular venus distension. So you may see some jugular venus distension, but you may also see facial swelling or you know the term edema. So that's something else I would watch out for as well. Now this wouldn't I think constitute per se a emergency. And I think that's the really important thing to remember is it wouldn't necessarily constitute an emergency. What I would consider to be an emergency of SEC syndrome is respiratory distress and ICB crisis. Theoretically, you can have hypotension, but the problem is is that the a lot of 1:23:29 people think, oh, it's because you're reducing preload, right? Because if you compress the SVC, you're getting less preload, less Venus return, less stroke volume critic output. Uh there's been studies that actually show that's not really the case. So it they actually say it's more likely cardiac compression. Um and so I would say that you're probably not going to see as much of the hypotension factor in a patient with SVC syndrome due to reduced venus return. It's more if it's a large enough kind of mass that it's actually causing the mass itself is compressing the heart not due to the compression of the SVC. All right, that is SVC syndrome. So you have a extrinsic mass that's compressing on the SVC. lung cancer, lymphoma, decreased movement of blood flow through there. Back flows through J. Back flows through subclavian. If it goes subclavian, arm extremity is you're going to get an edema and swelling of that arm, neck, and the veins are going to distend. I J, the vein of the jugular vein will distend. And then you get some facial swelling. I just wiped away the L and the I mean N. Oopsie. No, some 1:24:33 swelling there. But the real things that constitute an emergency is respiratory distress due to lingial edema from backflow into the lingial veins because again this is the internal jugular vein and these are some branches some lingial branches here right so this one here is the internal jugular vein and these are some branches that are supplying what what is this structure here let's write this out this is your up here the larynx all right these are the big things that constitute an emergency We'll see. SBC syndrome is very interesting in this patient. You're really thinking about this in a patient who has likely a known history of like lung cancer. That's a really really common one especially like central ones. Squamic cell small cell are the big ones. I'd say lymphoma but like a rapidly growing like one. So they have to have pretty significant lympadinopathy. Um Hodgkins not so much. Probably more of the non-hodkins like diffuse large B cell burka lymphoma. You'll see things like that. thymomas uh usually if they get a pretty large thymic enlargement like in T- cell alll maybe u but these are the things where 1:25:34 you got a mass that's compressing on the SVC we see this more likely in in ICU in a thrombotic nature where you got a clot in the SVC and that's reducing flow not as much as of a tumor on the outside extrinsically compressing the SVC but nonetheless let's say that you have these suspicions what would make you think about that you got a patient with a distended jugular vein that's one thing they have facial swelling edema um they maybe have a little bit of a bluish kind of like hue to it. Um usually worse in the morning interestingly. Um and then again arm and chest like upper chest and arm that all you kind of have some distended veins, some edema, some discoloration there as well. That'd be pretty concerning. But if I have a patient who comes in and they have like you know symptoms of neurological def like I and when I say neurological deficits more specifically when you have elevated ICP it's more of a decreasing level of consciousness maybe some nausea maybe some vomiting maybe some visual changes that's more likely to be the presentation you don't think about SVC syndrome and so elevated ICP can result because if you kind of 1:26:35 compress the SVC you reduce the drainage from the J and the drains your cerebral venus sinuses and so if those are compressed. If those aren't draining properly, it increases the blood inside of the skull. Monro Kelly doctrine says the ICP is going to go up and they can have some potential neurological symptoms. That's worst case scenario. And I think another one is the IG is also supposed to pick up feeders from veins around, you know, the larynx and the trachea as well, specifically the larynx. And so if blood kind of backflows into those you can actually get some hydrostatic pressure changes and fluid can actually exude into those spaces into the interstial spaces around the the larynx and you can get some lingial edema. They can get strider. They can get dysnia full-on respiratory distress. And so those are things to think about but again it's not something that you come to right off the get-go. You have to have a high degree suspicion and probably know that this patient has an underlying history of lung cancer or maybe lymphoma etc. Chest X-ray is not the best test. I think it's just an initial test in patients who come in with things like dysnia um or patients 1:27:32 who come in with things like hypoxia, respiratory distress, and you're really just doing it to rule out other causes. But if you happen to see a mediainal mass, which in this one a patient, you can kind of appreciate there's like an opacity here that that could be right around the SVC. I just need to get a better look at it. And so what I would say is you have to then determine their symptomatology. If they're emergent, we don't go and get a CT scan. we actually got to go in and both diagnose it and probably stent it at the same time. So, diagnostic and therapeutic intervention. Um, and but if they're stable, like they're not having any ICP changes, hypotension, respiratory distress, I can probably just send them to CT. And I'll get a CTH of the chest and I'll look at the Venus filling phase. And what I'm really looking for is, if you kind of appreciate this here, here's the aorta, here's the left lung, here's the right lung. They definitely have a little bit more of a kind of like a plural eusion here. But if you look at this, here's the SVC. And you can already appreciate there's like a mass here in the mediainum. And as you continue to kind of go up, this mass gets bigger and 1:28:28 bigger and bigger and bigger and boom, this thing's compressing the SVC. And so you you get almost a complete obliteration of the SVC. So that's that's pretty much diagnostic. I can't treat at this point like with this modality, but I can say, okay, now I have a diagnosis. I can actually reach out to my colleagues and say, hey, should I stent this or should I just reach out to, you know, oncology and say, let's do some chemo, radiation therapy and see if we can shrink it. So that's really what it comes down to. This is more of your diagnostic test. But if they're if they're emergent, right, then that's a different story. But again, I like the CT chess with contrast that venography study because it tells you, is there a reduced caliber of the SVC? Is there something compressing it? And and what is that thing? Is it a lung mass? All right. Is it a lympadinopathy, a really really bad one? Is it a thymic mass or enlargement of the thymus? Those are all really helpful in that SVC syndrome patient. But in the emergent one, we're not going to be doing an image in this kind of scenario. We need to be ready to diagnose and then if it is proven, treat. And so that's where we do an 1:29:26 invasive venography. We'll call out to our interventional radiology patient or team. We'll say, "Hey, I think I got a patient with SVC syndrome. Can you kind of snake a catheter up there and take a look?" They'll go intravascularly. They'll go up. They'll kind of like, you know, shoot some die, say, "Oh, there it is. We see the reduced luminal caliber of the SVC. There's definitely a lot of uh restriction and flow there." there and then what they'll do is they'll deploy a stent and they'll open up and kind of pack back open that SVC that we going to restore flow and help to drain the J so we reduce the cerebral edema uh drain the J so we help to reduce some of the respiratory distress and then relieve compression on the heart uh which can help to improve hypotension so those are the ways that we would kind of go about that and that's one of the beauties of this kind of dichotomy here all right I hope that makes sense so a patient comes in they have maybe ICP's high, maybe they have hypotension, maybe they have respiratory distress. You reach out to the IR team, they go up, they snake the catheter, they say, "Oh, there it is." Boom. Deploy the stent. That's going to be in those 1:30:24 emergent unstable patients where you're going to have to deploy that stent to remain back the patency of that vessel due to the tumor compressing on it. If the patient is stable and you got time, then you can just reach out to your radiation oncology team and say, "Hey, let's do chemo radiation. shrink this tumor down so we can reduce some of the facial swelling and edema uh arm swelling and edema etc. So that's going to be the definitive therapy and that's something I want you guys to think about. All right so next thing is going to be malignant spinal cord compression. So this one is actually a true like it's a scary emergency. We see this a lot in malignancies especially in the neurocritical care. You have a lot of patients who come in, they have unfortunate like neurological deficits, maybe bad blow uh bowel and bladder dysfunction. On top of that, they have potential motor and sensory deficits. You end up getting an MRI of the spinal cord and you find out, oh my gosh, there's an extra tumor. They have some vertebral body kind of erosion from metastasis. And then what do you do? You hit them with decadron and you start calling radiation therapy or radiation 1:31:22 oncology. You call the surgery team, neurosurgery team. and say hey is there any potential options to kind of like you know treat this underlying malignancy that's causing you know spinal cord compression. So thinking about that I think it's really important to understand which tumors are at highest risk. So first one is breast cancer. So breast cancer is definitely one if you have a breast mass this one can definitely spread easily. All right so let's remember breast cancer is a really really important one that loves to spread to the bone. Um another one is lung cancer. So lung cancer is another really really important one. We see this one spreading to the bone to the brain a lot. So definitely think about this one as well if you have a patient who has some type of a potentially vertebral body involvement. Um another one let's actually grab our structure here. Our little orange we see this one. Um and it's interesting because it's not osteoclastic as all of the rest of these are. It's actually osteoblastic. And this is going to be a little hint for you to think about prostate cancer. 1:32:23 So prostate cancer is another one that likes to spread to the bone. Um and the last one that I would want you guys to remember here is lymphoma. So lymphoma can definitely do this as well. All right. And again when we think about lymphoma there is different types. There's hodkins, there's non-hodkins. Um you're going to see this more in the non-hodkkins type. Another one that I will talk about very very briefly is multiple myoma. multiple myoma, which is usually when you have those plasma cells. That's another one that you also want to think about is going here and causing these potential problems. So, I'd say multiple myoma, lymphoma, specifically which of those non-hodkins, prostate cancer, and the last one is going to be lung cancer. All of these have the potential of doing what? Well, when you have these primary cancers, unfortunately, they can seed. So, they can seed into the bloodstream and they'll seed some of these, let's call them tumor emblei, if 1:33:24 you will. Um, we're going to seed some of these, we're going to call this tumor emblei. They're going to get into the bloodstream. And when they get into the bloodstream, they're going to spread. And where are they going to go? Well, they're going to go to your vertebral bodies, right? Sometimes sometimes these can even just invade directly into the dura. They can go right into the dura matter. And so what can happen is you can start off here. You can actually have an extra dural mass. You can have a mass right here. This is called a we'll call this one a extra dural mass. So that's one thing I would want you guys to think about is let's say here I have an extra dural mass and that is compressing on the spinal cord, right? Especially as it gets big enough, it's going to compress. Another thing that can happen here is let's actually show this in two ways. Let's say here we're going to go to this vertebral body. So we'll say it starts off, let's say this one seeds to this one and it starts causing destruction leads to some 1:34:24 cortical destruction of the bone. So now we have some destruction of the bone. But then what happens is when you destroy the bone, you start eroding the bone, it can actually start to let's say kind of erode and displace itself into that dural space, that extra dural space. And so that's where we start kind of getting these problems. It starts off as a little bit of vertebral body metastasis with cortical destruction and then erosion leading to it kind of extruding into that extra space. So it can either cause an direct extra dural mass or it can kind of do it indirectly by eroding the bone and then moving its way and kind of collapsing the vertebrae and kind of retropulsing its way into that space. All right, so that's what I want you guys to think about is an extra dural mass due to a primary cancer such as these seeding their tumor emblei getting into the bone getting into the dura causing these masses to form. Now when they form they start to obviously get big enough that they compress on the spinal cord. So they start compressing 1:35:26 on the spinal cord and as we get kind of compression or mass effect. So mass effect due to extra dural mass that's when we see the potential symptoms. So for example when you think about these we have neurons that go to a bunch of different places. you're going to have motor neurons, right? So, let's call these your motor neurons. These are your motor neurons. These are going to go to your muscles. And so, if you have compression, enough mass effect that you're compressing down on the actual spinal cord and affecting the motor supply to your muscles, then you're going to have decreased motor supply. That decreased motor supply, we'll talk about in a little bit here. that decreased motor supply. That's where we kind of have a lot of issues and that's where you'll start seeing things like weakness and potentially 1:36:28 changes in reflexes and flicidity and spasticity of a muscle. So that's one thing. Another one is you have compression of the spinal cord and it's affecting sensory neurons. So now these are supposed to be sensory neurons picking up information from things like Golgi tendon organs, right? You can even have your muscle spindles or this could be let's just kind of move this bone a little bit or this could be of the skin. This could be your pain, your temperature, your crude touch, your pressure sensation. So here you could have a decrease in your sensory supply and that's really important to remember at this point. If we have compression, enough compression that it's causing a decrease in that sensory neurons kind of action potentials. So here's your sensory neurons as such. The last thing here is we even have 1:37:30 autonomic neurons. Now autonomic neurons usually go to a ganglia and that ganglia will go to places like in this case the two really really important ones are the bladder and the bowel and whenever you have some type of compression here you have a decrease in the autonomic nervous system supply and that will lead to a lot of bladder and bowel changes. Now here's the question that you probably are starting to ask yourself a little bit. All right. I see the basic consensus here, Zach, of how mass effect leads to compression of the spinal cord, which leads to these neurons that are all coming out of the spinal cord leading to this downstream effect. What you really need to understand is how does the mass effect really do that? Just because you're compressing on a nerve doesn't mean that it's actually going to cause this effect. It can, but usually the mass effect, what happens is is it compresses your vein. So it leads to venus congestion. So there's there's veins that run 1:38:31 through the spinal cord. You're going to cause venus congestion of them. That's going to lead to spinal cord edema. Then the mass is also going to cause arterial compression over time and that is going to lead to necrosis or eskeeia to that portion of the spinal cord which will eventually lead to necrosis. So what you have to remember is that the mass effect can first first let's actually write this down first will lead to venus congestion that venus congestion is going to lead to spinal cord edema then the mass causes arterial compression this is later all right later down the line then over time if this is not addressed necrosis if these two you never take care of you will end up with permanent irreversible neurological injury. That's why it's so critical when a patient comes in with these neurological symptoms, the first thing that we see is the edema. What can I give them? 1:39:31 Steroids to reduce the edema. Get them to surgery or radiation therapy to start really treating them before they start to experience arterial compression, which can lead to necrosis, an irreversible injury. That is why it's super important to remember this. All right, so we got an idea here. Tumors seed, get into the bone or into the dura, cause the mass, compress the spinal cord, congestion, edema. Over time, necrosis due to eskeeia. If the nerves are being affected, it's either motor supply, sensory supply, autonomic. You could have one, two, three, you could have all of them. What would that look like? Let's talk about that for a second. So, this spinal cord compression is pretty scary. I don't want to go down because we're going to talk about this more in neurology block. But for right now, when we think about this, you know, we we have our cortical spinal tracts. And the cortical spinal tracts, you guys know, they move down through your your lateral 1:40:34 white column primarily. And then they kind of come in here and they give off these little endings, the termination point, right, to the anterior gray horn. And then these kind of move out and these go out and they go to your muscle. Right? Then they can continue down. So here I'm going to do like a dotted line. And then we're going to continue this one down. And then we're going to do a dotted line here. And we're going to continue this one down. And again can go here. Can go out and can go out. Either way, this is the primary one. This is your lateral cortical spinal tract, right? And then this is the anterior gray horn. And this one is going to give you a motor neuron that goes to your muscle. Usually what happens is is when you have a compression, you have a malignant tumor that is compressing on the spinal cord. If it compresses at this level, so I say that it's usually it's usually compressing extrinsically. So usually 1:41:35 what happens is at this level you compress the lateral cortical spinal tracts is usually what happens and then at this level you lose this supply. So you end up with a lower motor neuron lesion at the level of compression. So you end up with a lower motor neuron lesion at the tumor site and then you end up with a decreased signals going down because you're compressing here. So it's affecting at this level you're having a lower motor neuron lesion right? Then as we go down it's acting as the upper motor neuron and then you're decreasing the signals here. So you end up with an upper motor neuron lesion below the tumor site. And I think this is just basic. I don't want to go too crazy but I want you guys to have a basic understanding of this. And so yes, with these both they'll present with weakness, but usually with a lower motor 1:42:38 neuron lesion, you'll have maybe some decreased deep tendon reflexes. You'll have some flaccidity, right? Whereas with an upper motor neuron, you have hyperactive reflexes and spasticity. And I think that is somewhat beneficial, I think, to talk about in this potential scenario here. So when a patient comes in, they have a tumor, let's say that they have a history um of some underlying primary tumor, let's say breast cancer. All of a sudden, they come in with weakness of a lower extremity. And let's say it's just in this case, let's say it's of the left side and they have at one point they have a hypoactive reflex and they have that muscle just really flaccid, but then another area they have some spasticity. they have some hyper reflexia or clonus that could be again a very very concerning sign that you have compression a little bit higher up all right and so you may see a little bit of 1:43:38 a combination of these two but again I don't want to go too crazy it's the basic concept that you're going to experience overall overall there will be no matter what some degree of weakness all right some degree of weakness that is similar between these two it's just the other associated kind of things that come along with this that determines where the tumor may be. All right, but that's going beyond that's more getting into like localizing and I don't want to go too far with that. What I now want to talk about is the sensory supply. So again, when you think about these, you have different, you know, tracks. You have your dorsal column, right? And then you have uh we'll pick here. We'll pick red. So here's going to be your your lateral white column. And then we'll pick here in like this. Let's do black here. Let's say here's going to be your kind of your anterior white column. Right? So let's say that you have a mass that is compressing. So let's say that you have compression. 1:44:39 Let's say you have compression here. Right? There's a mass that's compressing at this potential site or you have a mass pressing at this site or you have a mass pressing on this site. Well, these are the areas that will start to experience neurological injury. So, what I want you to colorcoordinate these with is if it's the blue that's responsible for things like propriception, right? So, propriception and fine touch, you know, vibr we can go down the line here. I'll I'll do it like this. I'll put um fine touch. What else? Let's put this one. This one. Let's do vibration. We can keep going. Discriminative touch. I'm not going to go too crazy, but either way, you're compressing on this. You will experience a decrease in these symptoms or these these sensations, less vibration sense, less propreception, less fine and discriminative touch. If you compress on these on the red, 1:45:42 this is carrying more of your pain and temperature pathways. So it'll be a decrease in pain and temperature. All right. And then lastly, if it's the black one, if there's compression of this, this is more of your crude touch, your pressure sensation. There could be a decrease in crude touch and pressure. So that's what I really want you guys to kind of associate with these here is that again depending upon here's motor supply here's your sensory supply this is your your ascending tracks this is carrying all of your sensory information if you can press here this one you can press here this one you can press here this one all right the next thing here I don't I know you guys don't know this but behind the camera Rob has severe OCD he sees these black smudges and I think it kind of like literally it's like someone poking his brain So, I'm gonna erase that for him right there. All right, we're gonna keep going here. Um, 1:46:43 so the next part here is let's say that you have again this tumor. We have a compressing on the lateral cord of the lateral column. We get this weakness and then these lesions here of upper lower motor. You compress here on the ascending tracks, you get these sensory changes. Same concept here. You have let's do this in pink so we don't have too many different color color contrasts. Usually there's pathways that come down to your lateral greyhorns from the hypothalamus. And there's a couple different areas like your reticular uh formation, a bunch of different areas, but they usually go to your uh lateral greyhorn, which controls more of your autonomic function. So here, this is going to come here. This is going to go here, and this is going to go here. All right? So what I want you to remember is if you have a tumor that's here and it's compressing on the spinal cord, it's affecting the autonomic supply downstream, usually coming from areas like the pawns, right? 1:47:43 So any kind of tumor that's usually above like your sacral portion of the spinal cord like S2S4, as long as it's above that portion, when you have this, usually what you start to see is is you see a decrease in autonomic supply to the bladder and to the bowels. For the most part, early on in the disease, you then lose contraction of the detrer. The duster just doesn't contract. If the detrusor can't contract, what happens to the ability to urinate? It doesn't happen. And so, unfortunately, what happens to these patients is they experience what's called urine retention. But then, what happens is that urine retention leads to overflow. And that overflow can eventually lead to some overflow incontinents. So, you may see a little bit of both. It's usually in the form of like dribbling uh kind of as an effect here. But urine retention may be the way that these patients present and then that can then play out in the form of overflow incontinence. 1:48:44 Now another thing here is you're knocking off. So if I'm compressing here, I'm compressing these downstream p these upper pathways coming these autonomic pathways coming down through the lateral cord and then losing the autonomic supply here. I also lose autonomic supply here to the muscles that control the ability to poo. If my smooth muscle can't contract, just like the detrus or the smooth muscle within the actual muscular external can't contract, is am I going to be able to empty a turd into the toilet bowl? No, it's going to stay there unfortunately. And these patients experience constipation. Now, sometimes it can lead to like some overflow defecation as a result. But usually this may result in patients experience things like constipation. And again that constipation may lead to over time especially if it's getting severe it may lead to some overflow uh kind of like leakage or unfortunately defecation. So that's the things I want you to remember later on usually this is 1:49:45 early later on in the disease it starts to become a little bit more where you the patients can start to experience a little bit more of the incontinence and a little bit more of that overflow defecation but usually this is something that we would see with the bladder and the bowel changes. So when a patient comes in they say or they present with lower extremity weakness decreased sensation and one of the classic ways that they like to present this is like decreased sensation especially like you know of the lower extremities maybe it's fine touch propriception crew touch all of those things and then they combine that with bladder and bowel dysfunction you definitely have to think about spinal cord compression especially if they have an underlying history of a primary tumor that loves to spread to this What would you do? Get the MRI. The same concept here is because I you probably see, oh, I didn't finish this off. It's the same concept. I probably just didn't, you know, continue this down. This nerve will move down. Go here. So again, it doesn't matter. 1:50:45 The concept remains the same that either way you're blocking, you're compressing these nerve fibers. you're compressing these nerve fibers in the lateral column due to the extra dural tumor and that is knocking out the supply. So either way, it's the same concept here. Probably they got back pain. That's more likely the big thing. And then but I think neurological deficits, new onset neurological deficits where they're presenting with like weakness or paralysis of lower extremities, decreased deep tender reflexes, losses of sensations, um uh bladder and bowel kind of incompetence or incontinence in general may kind of peique your interest to think about. And if they have a known malignancy, things like breast cancer, multiple myoma, lung cancer, these are all tumors that like to spread to the bone um especially to the vertebrae. Um and so that's something to think about. Even prostate cancer can do that as well. So, that's something I would definitely be thinking about and I'd probably just get an MRI of the spinal cord right off the get-go because that's going to be the most clear distinction of the spinal cord. Is there compression or not? So, take a look at this. You can 1:51:41 kind of appreciate here. Here's the CSF in white. Here's the spinal cord in this darker color. Here's the vertebral bodies. Here's the spinus processes. And what do you notice as you kind OF GO, WHOA, WHOA. There is significant spinal cord compression. There's the loss of that CSF. And there's almost complete obliteration of the spinal cord there. So you have massive compression and if you kind of look here you can appreciate a tumor that's kind of an extra dural mass and that's really smashing on a spinal cord dude. So this is a concerning feature and I'd be pretty concerned. I'd probably hit this patient with dexamethasone reach out to my neurosurgical colleagues or my radiation oncology at the same time and say hey what do we do definitively here? But that's definitely going to tell me right away that this patient has some pretty significant spinal cord compression. Now again this is from a primary tumor that probably spread to the bone. It could have eaten away at the bone and then that kind of caused it to extend into the epidural space or it can just go right into the epidural space and extend there on its own. So either way we got a primary tumor that has caused some 1:52:36 problems in the spinal cord. You got a patient coming in, they have a known malignancy. Maybe this is breast cancer, multiple myoma, they got lung cancer, they got prostate cancer. Now they're coming in. They have new onset uh weakness of the lower extremities. They have a decreased anal wink reflex. They have decreased detention reflexes. They have loss of sensation. They have bladder urinary inc bladder and bowel incontinence. You get an MRI, you find that they have spinal cord compression. You see the mass extra smashing on it. What do you do first? Dexamethasone right off the get-go to reduce the vasogenic edema. That's the first thing. What's the next thing? You're going to pick up the phone. You're going to call radiation oncology. You're going to call neurosurgery. Have them take a look at the image. have them examine the patient, say which one of these therapies is best to decompress them and get that tumor to have less pressure on the spinal cord. And if you do that, you have a good chance of preserving some neurological like long-term paralysis. So again, here's the image. We see it. Oh, let's get them started on dexamethasone. After we do that, reach 1:53:31 out to radiation oncology or neurosurgery. What would the radiation therapy do? It's going to help to target it and shrink that tumor if we have some time. But oftentimes more than not, from what I've seen, we have to peel that muffin cap back blue and release that compression immediately with neurosurgical interventions. All right, so hypercalcemium malignancy. This one's really interesting and the reason why again I talked to you about it is it is kind of a paranoplastic thing and we'll talk about that in that video. That's why it's so good. I think one of the things I think we hope to try to accomplish here at Engineered is that you'll see things overlap a lot and that's what you want. You try to want to you really want to be able to make connections between multiple different disease states and pathophysiological processes because I think it helps you to stay in that memory center a little bit longer. So we will talk about this again in paraneoplastic syndrome but it's really interesting because when we talk about hypercalium malignancy you wouldn't think of this as kind of like an emergency but it really can be. I think one of the scariest things is the 1:54:29 massive degree of dehydration that these patients can experience and the severe bone pain and fractures that can happen as well. So, how does this really occur? Well, one potential problem and it's probably going to be clear as day to you once you kind of see it is lung cancer is a really common one. Now, if you guys are if you guys have watched the videos right now, you're probably screaming, "Oh, I know which one it is." Which lung cancer do we commonly see leading to hypercalcemia? Come on, scream it out. Ah, I know you guys said it. It is usually going to be, and we'll do it here in black so we have a good contrast. It is usually going to be squamicell carcinoma and that's usually more central, right? Heavy heavy smokers. So squamicel, we'll put squamic cell carcinoma of the lung is kind of a nasty one. And the reason why is this this can secrete these tumors can secrete something called parathyroid hormone 1:55:29 related peptide. Now parathyroid hormone related peptide and when it's made by this tumor we consider that a paraneoplastic syndrome. What happens here is that this hormone can act on your bone tissue. It can really act on your osteoclass and it can really help to activate osteoclass. So here here we got an osteoclass. Let's stimulate this dude. If we activate osteoclass, what do we know about these? Well, we know that they release things like hydrochloric acid and acid phosphotases. I mean hydrochloric acid and different types of collagenasis, sorry. And what those do is is they start to kind of break down the bone, right? And as a result, they increase what's called bone resorption, which is kind of like you're basically eating the bone away. And what that's going to do is that's going to liberate calcium free from the bone. So osteoclass will become activated. They'll chew away the bone. That bone 1:56:29 absorption will then liberate calcium into the bloodstream. And there goes one way that calcium can go up. So PTHP really what it does, it works on the bone by helping to chew up more of the bone. And that's going to liberate calcium into the bloodstream. PTHrP also can act on the distal tubular cells and what they do is they help to increase uh the movement of calcium. So they basically play a role in increasing calcium reabsorption. So what I'm going to do is I'm going to move more calcium. I'm going to stimulate this process. Let's amp this up, bro. We're going to increase calcium reabsorption. So if I have more calcium just because I'm going to run out of room reabsorption bruh more of that calcium is going to move across the distal tubule into the blood and that is going to lead to an increase in the calcium. So that's that's the ways that PTHP works. Now there's another thing cancers primary malignancies breast 1:57:32 cancer big one. You know what another one is? You know, when we think about this one, I I'd say this is a really really scary one. It's usually multiple myoma. Multiple myoma is a really really nasty one. Breast cancer, definitely think about it. But I'm really really want you to think about this, especially especially with multiple myoma. So multiple myoma and breast cancer. Now with breast cancer, the bone really just I mean the cancer itself. Here's the tumor. it kind of seeds and it gets into the bone. It causes like this litic lesion and then eventually these start kind of like chewing away and you release this kind of like calcium. You have the bone absorption, right? Multiple myyoma can do this through other mechanisms as well. We're not going to go down that line. What I want you to know is that breast cancer, yeah, the tumor itself can cause the litic lesion. Multiple secretes things like osteoclass activating factor and rank lians and things like that. All of these things do the same kind of concept. they start chewing away the bone. So in patients who have multiple myyoma and breast 1:58:32 cancer they can invade the bone tissue. When they get into the bone tissue they can start kind of activating osteoclass but they can also kind of deposit into there and start eroding the bone tissue. They lead to osteo litic lesions. So that's what I really want you to remember. So litic lesions are a problem. All right. So we got tumors causing litic lesions. We got tumors secretreting PTHP. What if I got another one? I have a lymph node here and this thing is as big as a as a Mac truck because a patient has a massive massive massive tumor here. They got a bunch of different types of lymphocytes that are accumulating and accumulating and accumulating inside that lymph node. Now, the problem with this is you might be like, "Okay, how's this even relevant, bro?" Well, in patients who have lymphoma, they increase, especially lymphoma. So let's say here we have lymphoma and you probably ask oh which one is it Zach? Is it Hodkins noddkins? Believe it or not it's actually Hodkins lymphoma. Now with Hodkins lymphoma what happens is there's an increase in what's called alpha 1 hydroxilase. 1:59:34 Alpha 1 hydroxilase is an enzyme that basically what it does is is it helps to convert 25 hydroxy. So it converts what's called 25 hydroxy vitamin D and converts it into one comma 25 dihydroxy vitamin D. This is the active form of vitamin D. What's the name of this? Calcy triol. This is the active form of vitamin D. So what happens is alpha 1 hydroxilase basically just puts an extra one on here. So it puts an extra hydroxy group on here. So what it does, it stimulates this step. And if you stimulate this step, you're going to get more of calcatrial. Why is calcatrial important? Well, calcatrial, it, believe it or not, it does actually work in these pathways, but more often than not, for your exams, it talks about how it works in the git. And what it does, it creates like little channels. Creates like little channels. We'll do a couple of them here. Creates like little 2:00:36 channels for calcium. and it says, "Hey, bro, we didn't have as many of these. I'm going to open up some channels here for you so that any kind of calcium that's in the git, boom, get it right into the bloodstream." So, any calcium that's just kind of like mossying along here, boom, boom, boom, boom. And then what you get out of this is what? You get increased calcium absorption in the git. So increased calcium absorption that increase in the calcium absorption is going to result in what? Boom. Hypercalcemia. So now we got the hypercalcemia. So here's what I want you to be concerned about in these kinds of scenario where patients have litic lesions due to metastasis. they have uh some type of high PTHRP from a squamic cell carcinoma or elevated calcatrial from like lymphoma. Either way, the calcium goes up. What we 2:01:38 would consider to be severe hypercalcemia is to the point where it is high enough that we can define it in two ways. One is it's severe, meaning it's greater than 14 milligrams per DL, or they're symptomatic. So you can still technically have severe hypercalcemia or emergency I should say even if the number isn't greater than 14. It's just oftentimes these go hand in hand. As the number gets higher you become more symptomatic often. Well the question that we then got to talk about is what makes these patients become symptomatic? How do we actually identify that? Well, sometimes, yeah, you may find this on a lab value, but hypercalcemia, a malignancy, often times this can present clinically because it's rapid and it's usually severe. What would happen here is let's say that a patient has a high calcium. So, you have hypercalcemia, right? So, increased calcium in the blood. Well, what happens is is that calcium can be freely filtered. So, if you don't have a 2:02:39 problem with like glometration, what's going to happen? Well, it's going to filter right out, right? So all this calcium that's hypercalcemia that's going to lead to hypercalce ura. All right. Hypercal. Let's actually write that down. Let's actually write that down. What is this called? Hypercalceura. So we'll write calcy ura. Hypercalcemia can lead to hypercalcyura. Hypercalceura means you have more calcium present in the urine. If you also have things like oxalate present and phosphates present, guess what you lead to? you lead to stones. So calcium containing stones. I'm not going to write both of them, but it's usually oxalate. So containing stones, that's usually calcium oxalate stones, calcium phosphate stones. Either way, they accumulate enough that they start to obstruct your actual renal system. And so these patients can develop something called nephrolithasis. All right? And so nephilothiasis 2:03:41 is the is a one big concern that we can have nephiliasis. How will these patients present flank pain right? So they may have flank pain. They may have associated nausea, vomiting, hematia. Often times what we think about when we think about the pneummonic of hypercalcemia is stones, bones, groans, thrones, psychiatric overtones. So with stones we think about kidney stones, right? Right? They can have an increased risk of nephrolithasis stones bones. So another thing here is because of PTHrP because of litic lesions from multiple myyoma because of litic lesions from things like breast cancer or even sometimes elevated costatrial and lymphoma. You're chewing through this bone, dude. Right? You're ripping apart the bone and these litic lesions. What happens is is you lead to some significant bone pain, right? So, they're going to have bone 2:04:41 pain, but I think the most concerning is just just think about this for a second, dude. I mean, just really really think about it. You got these litic lesions. Look how little of the bone you got left that you just eroded to. Tell me that's not an easy way to snap that bone in half. So, not only can bone pain be a potential, but also you can lead to pathological fractures, right? And that's I think where it gets really, really scary is is the risk of pathological fractures. If it's chronically over time, obviously this can lead to things like osteoporosis, which again lends to that risk of pathological fractures. So bone pain, pathological fractures is another one. So stones, bones, groans. Now this is I I think it's important to remember this one because yes, it can cause changes in your smooth muscle contraction, but one of the things that we talk about with um pancreatitis. So it does increase the risk of pancreatitis. Um this is hypercalcemia. So hypercalcemia I don't want we talked about this in the pancreatitis lecture. I don't want to like spend time talking about this too much because I don't think it's super relevant to this. But 2:05:43 I'm going to quickly tell you without writing it all out. I just want to make sure that you guys understand this. The calcium can activate pancreatic enzymes, zyogens, pancreatic proteasis, lipaces, amalaes, nucleases. all of those things get activated. So if you cause um activation so stimulation of pancreatic zyogens pancreatic zyogens all of those different types of inactive pancreatic proteasis lipaces amaises guess what it's going to do boom you activate it inside the pancreas when it's supposed to be in the douadenum dude you're only supposed to activate in the dueum if you activate in the pancreas it's going to start digesting the pancreatic tissue pancreatic tissue is made of proteins lipids nucleic acids carbohydrates, you will start digesting it. So, that's one thing that we worry about. And if you have pancreatic pain, what's it? Stones, bones, groans, oh, abdominal pain. Thrones, this is the one I actually think is really scary. When a patient has hypercalcemia, 2:06:44 hypercalcemia is kind of a it's actually kind of cool this mechanism. And again, if you guys have watched our videos, you know this already. There is receptors that are present on the collecting duct. These are your V2 receptors. Your V2 receptors are what respond to a hormone called vasop prein. Um, also known as ADH. When calcium is way too dang high, it basically blocks this interaction. ADH ain't doing ain't doing what it's supposed to be doing. We block the ADH. What is ADHD supposed to do? ADH is supposed to open up aquaporin subunits. Usually this is aquaporn subunits, right? And um when we open up the aquaporn subunits, guess who comes through? Water. Aqua. But if you have no ADH that is theoretically present because it's being blocked by high calcium, this water that's supposed to be reabsorbed. It's supposed to be driven by ADH. Right now, you don't have this signal. There's no 2:07:46 stimulatory signal. So we'll say that's an inhibitory signal. Are you going to allow for this aquaporn to be open? No. Is water going to go through? No. So you have decreased water um reabsorption. All right, let's write that down. Decreased water reabsorption and as a result the water is going to be lost into the urine. You're going to peep out a lot of water and you're going to have a increased amount of watery urine. So increased what we call dilute urine, but it's going to be a lot. So we call that poly ura. If you lose a lot of water in the urine, you don't reabsorb enough of it. What can that lead to if that happens severely? It can lead to two things. One is it can lead to dehydration in the form of hypoalmia and the sodium can go up when you have less water in comparison to sodium. And so we risk hyperetriia and we risk 2:08:48 dehydration because we're not bringing as much water as we should into the vascular system. Dude, that's why when they say stones, bones, groans, thrones, you're peeing all the time. This is the scary one because of the risk of dehydration. We have to give these patients a ton of IV fluids to help to replete their vascular space. The last one is psychiatric overtones. So psychosis is a very very concerning one as well. That'll give you the big thing to take away from the hypercalcemia malignancy. Hypercalcemia malignancy is again this one's interesting because you don't really have a lot of the times symptoms of it but if you have pretty severe hypercalcemia I'm talking greater than 14 um you can you can sometimes get pretty dehydrated with this one. So you can get significant dehydration. So polyura but again you think about the stones. So you know gallstones is kind of a risk factor but primarily it's going to be a nephrolithis. So kidney stones, bones, they're going to have bone pain, osteopenia, pathological 2:09:49 fractures is another one. Crohn's, so abdominal pain. This could be due to kind of changes in their overall GI motility, but also pancreatitis is a big one. Peptic ulcer disease, maybe kind of you can get some ulcers as well. That's lower risk though. Um and then thrones is polyura. So they can develop ne nephroenic DI. They can lose a lot of volume and they get pretty dehydrated. Um and then the last one is um your psychiatric overtones. So things like psychosis and confusion etc. That would also be something to think about. But I think the big thing here is when a patient has hypercalcemia if they have a serum chemistry that comes back and it's greater than 14 oh that's severe. Or if they have greater than 12 but they're symptomatic that's also severe. And so what do we want to do is we want to prove that. So I like to get an ionized calcium. The reason why is it tells it tells you the exact true amount of free calcium in the blood. If that's elevated you you're you're in some trouble. So then you got to determine is this PTH dependent or independent because if PTH is high then it's coming from the parathyroid right it's likely coming from the parathyroid and then you this 2:10:50 isn't a malignancy process if the PTH is low then that would tell me that something else caused the calcium to go up and that suppressed the parathyroid to decrease the PTH level right so that's what I want to check but also when you order these panels for hypercalcemia you also often times will order like a PTHRP you'll get a phosphorus you get a calcat trial which is your vitamin D level and you may also add on an alkos level. What I like to do is look at the PTH first. If the PTH is low, it's PTH independent. And then I want to know which of the other one is high. If the PTHRP is high, it could suggest squam cell carcinoma of the head, neck or lung. If calcatrial is high, it could suggest lymphoma. And that would be some ways that I can determine right away if this is a malignancy of the lung, a malignancy of the uh the lymph nodes, right? Right off the get-go, right? But let's say that the PTH is low, but the PTHRP in the calcata trial is normal. That's where I would maybe consider the ALK FOSs because if the ALK FOSS came back super high, there's lots of bone turnover. And that could suggest some type of like 2:11:50 litic lesions. And so what I would do then is I'd probably get a skeletal survey. I want to see is there litic lesions of the skull? Is there litic lesions of the ribs? Is there litic lesions of the vertebrae? Because that could suggest things like breast cancer, multiple myoma, lung cancer, so many primary cancers that spread to the bone. And so that's what I do. And it would look a little bit like this. You can see and appreciate there's a bunch of skullitic lesions here. You can appreciate some litic lesions here. Um, and you can even do it right here in the rib. You can see some right there. You know, so this I'd see this a lot in multiple myoma. Breast cancer can also do this. Lung cancer can do this as well. But yeah, the bone one that that's that's a nasty one. So that's kind of the way that I would think about the hypercalcemia malignancy. This is a patient who has some type of squam cell carcinoma of the lung. They have some lymphoma. Maybe they have a primary tumor where they're getting lots of litic lesions of the bone. Breast cancer, multiple myyoma, really, really big ones here. Lung cancer. They have these tumors and they're causing the 2:12:46 hypercalcemia. Well, the first thing is when you get hypercalcemia, that hypercalcemia, especially when it's greater than 12, 14 range, it can cause massive dehydration. I need to give back those fluids and maintain you. So, I'm going to hit them with IV fluids right off the get-go. probably two three lers normal saline most often that's going to be when it's severe greater than 14 or they're symptomatic and usually symptomatic plus greater than 12 I'll hit them with this the next thing is once we've addressed the most acute thing which is the dehydration I got to get that calcium down the fluids aren't going to pee out calcium that people think that's going to be the answer it's not it's just going to help to replace the volume and maintain you the way to get the calcium down is going to be calcetonin at first so we got to treat the calolytic lesions with calcetonin and then after that we're going to pick something like bisphosphinates or domab and if that doesn't work then we reach to dialysis is going to be the way that we go but here let me let me let me take a second here so we have something called rank lian usually plasma cells and B cells 2:13:45 make this and what it does it acts on the rank receptor on our osteoclass that activates osteoclass to release hydrochloric acid collagenasis this kind of erodess at the bone releases calcium and phosphate from the bone which can cause litic lesions but also can cause hypercalcemia The other thing is that on these osteoclass, they have receptors for calceton. And calcetonin is great because it's very quick. It's short, you know, onset. So, you're going to quickly get it some some bang for your buck when you give this drug. And so, what's going to happen is it's going to hit the osteoclass receptor. When it does, it shuts down the hydrochloric acid collagenase. That shuts down the litic lesions further. That shuts down the calcium resorption from the bone. And then it also activates osteoblast to help a little bit with the bone deposition and putting some of the calcium back into the bone. So you get a quick drop in the calcium, but then we need something that's going to be a little bit more longterm. So calceton is just kind of like a short-term patch. You need something longer term. That's where bisphosphinates or domab come into play. So bisphosphinates are going to be 2:14:40 probably the more powerful one. You may use those um you may use denosimab in things where a patient has severe renal failure or really bad kidneys and bisphosates are a little bit tough on the kidneys sometimes. Osteoncrosis of the jaw, severe esophagitis, and they're just, you know, they just have some kind of like contraindication to it. You may use denosimab, but bisphosates are great. This is your alendron, your zylendron, your paladron, all those guys. What they do is they they basically kind of like inhibit the osteoclass from proliferating. So, you don't have as many of those to release hydrochloric acid and collagenase and rip up the bone. The other thing is it actually kind of kills these osteoclass. It causes apoptosis. So you have less of these again to cause hydrochloric acid release and collagenase release and that leads to less of the destruction of the bones. So that's one of the beauties of bisphosphinates. Denosmab kind of comes back to this rank lian. So domab is a monoconal antibbody. It's going to bind to the rank liand and when it does that it then can't bind to the rank receptor and then if you can't bind to the see how these bind you can't bind to the 2:15:38 rank receptor you can't trigger this whole process and so you don't get the litic lesions and the calcium released from the bone. So it's kind it's pretty cool to think about that. One other drug that you could do is if you give them on fluids, you give them calceton, you give them bisphosphinates or domab, you can consider steroids and the patient has lymphoma because steroids will inhibit the lymphoma from increasing alpha 1 hydroxilates which causes the calcatrial production. All right, so that's one other consideration. All right, the last one is malignant cardiac tampenon. Now, out of all of these, I'd say this is the like it's the most dangerous one. This one will actually like I'm not killing it will it will kill you. Most of the patients who get cardiac tampenot most of them go into cardiac arrest because it's a pretty severe kind of condition. So it is a really important one but I think in the the the the gambit of all of the ones that we talked about it's probably the least likely one that you'll be tested on the exam. When it comes to cardiac tampenod, there is two different types. Um, if you will, with regards to I'd say more hemopericardium is usually things like 2:16:39 you have an aortic dissection. You you get hit in the chest with a tomahawk and you puncture through the left ventricle. You have some unfortunate left ventricular rupture and your just left ventricle explodes because you had an MI there and then blood leaks into that space. you had some cardiac surgery or you know maybe a radio frequency ablation that you just happen to create a small hole in in a part of the one of the chambers of the heart and the blood's kind of leaking out. So there's a lot of different things with those those develop rapidly and it only takes a small volume of that rapid blood blood accumulation to increase the inparicardial pressure boom you squeeze on the heart and it just doesn't get enough blood flow in and blood flow out. With these usually malignant paricardial eusions, those are slower eusions. So they're more cirrus or cerosanguinous. This is things that you think about with like you know pericarditis, you know, tuberculosis. Um you think about this with malignancies, you know, and so that's what I want you guys to talk about here and understand. So with cardiac 2:17:40 tampenodon, we have a couple different, you know, cancers that I'd say can spread and it's usually just things that are close in proximity to the heart. And so think about it. The lungs are pretty close in proximity. Oh my gosh, look at that thing. That that thing got butchered. So there's a butchering lung there. But lung lung cancer can definitely be a very very common one. So lung cancer is a big one. Um, another one is the boobies. Breast cancer. This is another one where this can easily spread. And I'd say the last one is going to be um some type of lymphoma. So lymphoma can definitely do this one as well. So lymphoma, breast cancer, and lung cancer I'd say are pretty common malignancies that these can actually start to seed their tumor emblei or you know they can they can spread directly and they can go and invade the paricardium. So here we have these tumor cells. They're all over the paricardium. 2:18:40 What happens is is once these kind of uh tumor cells spread to the paricardium, they increase the capillary permeability within the paricardial cavity. So you have you have vessels that are on the parietal in the visceral paricardium and what happens is you're going to cause those tumor cells to agitate the vessels there. They're going to they have cytoines like interlucan one, interlucan 6, TNF alpha. They're going to increase the capillary permeability and fluid is going to start leaking out. But the problem is is that this fluid leakage. So let's kind of represent this as dots here. These blue dots. This is the fluid that's kind of leaking out. Right? So here you're going to have the tumor. Let's call these tumor emblei again. So tumor emblei. They're going to get into that paricardium. Right? And they're going to increase the capillary permeability. And then what's going to happen unfortunately as a result here of them increasing the capillary permeability 2:19:43 is that fluid will start leaking out and over time you'll have what's called a paricardial eusion. Right? So it'll start off with just a little bit of fluid and you'll get what's called a paricardial eusion. Now here's here's what I want to write out. This paricardial fusion again it's usually going to be more cirrus or maybe even a little bit cirrus but primarily cirrus. But the paricardial fusion doesn't mean that you have cardiac tampenon. Once the fluid inside of the paricardial cavity builds up enough where you have enough volume and pressure inside of the paricardial cavity that it's actually compressing the right atrium first, then usually it's enough pressure to compress the right ventricle. And if it's severe, it can compress the left atrium. So it's usually in that f that fashion that order. Usually enough fluid accumulates over time that it gets large enough that the pressure inside of the paricardial cavity increases that it compresses the right atrium then the right ventricle 2:20:44 and in severe cases the left atrium. You have to understand that when this compresses so here we're going to say compresses let's actually write this down for you which one is in order. Right atrium then right ventricle then left atrium. These are going to be the way in which we kind of compress these. What happens is when does this occur? When does this fluid get to the point where it starts to squeeze in the heart? If you have a little bit of fluid, it's not really compressing in the heart. At what point do we get to that? So, here's what I want you to understand. Let's say here the dotted line. This is what's called the parardial stretch limit. So, this paricardium has got it's got a little bit of give, right? Has a little bit of give. In other words, let's say fluid you get blood that goes into the paricardial cavity. It stretches but you fill it up quickly. It doesn't have enough time to stretch. It reaches this paricardial stretch limit too quickly. Not enough time to actually accommodate that space. 2:21:44 Starts to then squeeze on the heart. That's when you get cardiac tampon usually from a rapid development. So let's say in situations like a hemoparicardium we'll represent that in blue. Here's volume over time in the x- axis and intraaricardial pressure on the y- axis. And when you have this scenario, whoop, that's rapid. That's a rapid development. This is usually usually your heo paricardiums. Most of the time, this is your hemoparicardium where you have rapid development. It's rapid development. All right? So something had to develop pretty quickly. Whereas in these scenarios, it's usually slow where you're accumulating. I actually have to kind of move a dotted line here. So, I'm going to have to go dotted. Boom. Boom. Boom. Boom. Boom. Boom. Boom. We'll kind of do it like this. And then we reach that limit. So, what happens is that in these patients, it's slow. They're slowly and progressively increasing volume, increasing volume, increasing 2:22:45 volume. Because what happens is you get a little bit of volume, the paricardium has time. It stretches. It accommodates. You get a little bit more volume over the next day or two. It stretches. It accommodates. A little bit more volume. Stretches. Accommodates. But eventually you get to a point where it says, "I can't take no more volume, bro." And you've reached that stretch limit. It can't accommodate for that space. And then what happens? It squeezes on the thing that it's right next to, which is the right atrium, right ventricle, left atrium. So this is usually slow development. All right. Thus the time on the x- axis and then here this is usually your cirrus paricardiums. This is the ones that usually are more likely to develop from things like paricarditis, right? Things like malignancies, tuberculosis, hemoparicardiums. These are very very rapid. They develop very quickly. And so that's kind of the differences that I want you guys to understand. With malignant paricardial eusions that can lead to tampenod, it is a slow 2:23:46 development of paricardial fluid over time due to the tumors seeding embleizing here and causing increased capillary permeability. Once it gets to the point where it no longer can stretch anymore that paricardium, it compresses in the heart. What will that do? Well, it's mainly the right heart. Yeah. So, you're going to reduce venus return. What happens if we reduce venus turn? Let's let's talk about this for a second. We talked about this in cardiology. So, I don't think we need to go too crazy, but you guys know that in cardiac tampenod, there is something referred to as beex triad. Beex triad. We can say that if you got enough fluid in here, all right, you're supposed to have a little bit of paricardial fluid, but not like a massive amount. When I got a lot, and I'm trying to oscultate. So, here I I got my I got my stethoscope right here. Right. And I'm going to try and listen. I'm going to try and oscultate over the heart. When I do that, I should be able to listen to the heart sounds. Right. So, the heart sounds should be traveling towards my stethoscope. But if 2:24:47 it has to go through a further distance of fluid, that's going to dampen that sound. And so what happens is the sound that gets picked up by the heart uh by the stethoscope is going to be sounding like it's very distant and muffled. So what you'll have is you'll have what's called distant or muffled heart sounds. And that's just because whenever you have that S1, S2 that's being produced, right? So you get that S1, the S2 heart sounds, those are going to be very muffled. And that's what I want you to guys to remember. And that's just because of all that fluid. Now, another thing that can happen, it's not super like, you know, consistent upon this, but you know, whenever you put like EKG electrodes, right? So you you actually put the electrodes on the chest, the electrical activity that has to get picked up by the electrodes also reduced. And so guess what else you have? You also have decreased QRS voltage. And so that is something I want you guys to think about, but again that goes this is going a little bit beyond I don't want to take it too far. This is something that you get more in your your 2:25:47 cardiology um section. So we'll we'll stop it there. What I wanted you guys to know is that when this paricardial fluid is it's it's building, right? I got enough of this paricardial fluid in here that it's really really building. It's reached the paricardial stretch limit. As it reaches the paricardial stretch limit, this is where we get kind of scared. We already talked about this a little bit, but look what we got compression of the right atrium. Look, we have compression of the right ventricle. Look, we have compression of the left atrium. So, here's the problem is when you have this mass effect. So, you get compression here, compression here. This is the big thing. Blood is supposed to move down here and then right in here. But this is being impeded. It's being reduced. So, what you're getting is is you're getting a reduction. What's really happening here is you're getting a d a reduction in venus return because the right heart is the one who's supposed to be getting a lot of blood from your systemic circulation. Right? When you get a reduction in venus return, you drop your preload. When you 2:26:49 drop your preload, what happens to your stroke volume? Drops. What happens to your cardiac output? Drops. What happens to your blood pressure? Drops. What can this present like? Oh, dude. you can get a patient who is in obstructive shock. So that's what I want you to know is that a drop in venus return drops preload, stroke volume, cardiac output, blood pressure and this can present. This is the scary thing. These patients can be sick. They can have very very low blood pressure that they're depending upon vasopressor support or fluid resuscitation to try to be able to keep them alive. All because of what? because of right atrial right ventricle compression because of the paricardium that fluid and that right there is the basic pathophysiology right here's another problem to think about because you got venus return that's reduced 2:27:51 blood is supposed to be coming through two ways one is through the inferior vennea right so it comes through the inferior vennea and it comes through superior vennea, right? If you're compressing the right atrium, is blood going to go down? No. And blood's going to backflow. It's going to backflow into the IVC and it's going to back back backflow into the SVC. Now, dude, we don't we can't see if someone's got an inferior vennea that's big and plethoric. You could if you did an ultrasound. So if I did a echo cardiogram, I'd be able to see that they have a very enlarged IVC. If we really want to, I will write that. So sometimes you actually can get you get an echo. You get an echo. You'll see IVC dilation, but that's non-specific. There's a lot of things that can do that, right? So the echo will show the presence of IVC dilation. Right? So 2:28:51 that's what I want you to remember there. But what we actually look for is clinically something else. What will happen if blood backflows from the superior vennea up to the brachioalic? Where's it going to go? Jugular vein. So another thing that happens is it goes and causes jugular venus distension. Right? So you're going to get jugular venus distension. So oftent times Beck's triad is jugular venus distension. Right? So here's let's say one. The second part of the triad is low cardiac output. Low cardiac output. And the third is distant or muffled heart sounds. The last thing is pulsus paradoxis is sometimes kind of tested. They can kind of throw this one in there a little bit. And all I want you to think about with this one is that when you see a patient who's taking a deep breath in, normally when you take a deep breath in, you increase your venus return, which should actually increase your blood pressure a little bit because you're theoretically 2:29:52 you're increasing your cardiac output. In patients who have cardiac tampenod, they're compressing their right heart. And so whenever they try to take a deep breath in, they do the best that they can to suck blood down into the right side of their heart. But unfortunately they don't get enough venus return enough stroke volume enough cardiac output and their blood pressure drops during inspiration to where it's greater than or equal to 10 millm mercury drop in their systolic blood pressure during inspiration. That's a paradoxical decrease in the systolic blood pressure during inspiration. That's called pulsus paradoxis. It's not exclusive to cardiac tampon. You can see this in things like asthma and other conditions as well. You can even see it in tension pumothorax. But what I want you guys to remember is that in cardiac tampon I've remember Beex triad as we said here here and here in the possibility of pulsus paradoxis. What makes you think malignancy and underlying history of a primary cancer? How would you really determine this? The unfortunate way that we can truly only determine this is we'd have 2:30:52 to do a biopsy. I'd have to biopsy the paricardium. oftentimes we would find the underlying cancer like a lung cancer, breast cancer, lymphoma. But with these oftentimes the only way that we can truly diagnose the condition is to do a paricardioentesis after we've done an echo and take that fluid off and if they have improvement in their hemodynamics, we can technically diagnostically and therapeutically figure this condition out. All right, cardiac tampenon. So with cardiac tampenodon, this is not something that you think about with a malignancy, right? But if they have a known malignancy, so I think about this in breast cancer, that's a pretty common one. lung cancer really think anywhere in that vicinity. So I'd say breast, lung is a really really big one and lymphoma. Lymphoma is another one as well. I say those are your three cancers that can spread to the paricardium and when they do they cause a lot of that cirrus kind of production of fluid. They cause more leakiness of the capillaries and you can get a paricardial more of a cirrus paricardial eusion and as that grows and grows and grows it reach the paricardial stretch limit. Can't stretch 2:31:47 anymore. So what does it do? squeezes on the heart like it's squeezing out some orange juice, right? And because of that, you can get things like nuance of hypotension from obstructive shock. You can get distant heart sounds because you got fluid around the heart that you can't hear it as well those heart sounds and JVD because of reduced filling into the ventricle. So it backs up into the jugular veins. So at this point you say, "Okay, what would this make me think? This this is screaming like Beex triad, right?" Subex triads is that constant new onset hypotension and distant heart sounds and JVD and really the hypotension is kind of interchangeable to a degree with a reduced cardiac output. It's just the way that we think about cardiac output. It could it correlate to their blood pressure? It can't depending upon what the resistance is and how that's adjusting. But yes, in this scenario, an echo is going to be the first thing that I would do. The echo is is going to tell me is there a paricardial eusion? Is there collapse of the right atrium and the right ventricle? Maybe even the left atrium that's occurring during diasty. That's really going to be the key. If you see 2:32:41 something like this, you run for the hills. No, no, no. You got to get ready to stick a needle into the paricardial cavity cuz you can see there's a paricardial eusion for sure. And then you can see here's the right ventricle. And that thing is like fluttering as crazy as could be because it's getting compressed during filling processes. And the right atrium is being compressed. Left atrium not as much, but I definitely see a pretty significant degree of compression here um from that paricardial fusion. So I'd be concerned about par um paricardial tampon. And so what I would do is I would get a paricardioentesis. I would do a subzyoid approach. You know, that's one way you can go about it. You can also do different parernal views and kind of t that way or an apical view and you can tap in that way. Either way, you got to get that fluid off. And the reason why is there's um a writer for internet book of critical care. Um his name is Josh Varcus and he he talks about how one of the best ways of really determining a patient who has cardiac dampen by doing a paricardiosis. Because if you think about it, if you tap in, you pull off maybe a couple cc's, 10 cc's, 20 cc's, 2:33:38 whatever, you're removing fluid that's giving more time for the paricardium to stretch. It's not squeezing on the heart as much. And so what should happen? You should see an improvement in their hemodynamics. And so if I see an improvement in their hemodynamics, I can then therefore diagnostically and therapeutically say that this patient has cardiac tampon. So it's kind of a beautiful thing when you kind of combine those two tests. All right, malignant cardiac tampon. We kind of already talked about this in the diagnostic algorithm where you have a patient with a beex triad. They have maybe underlying malignancy. You get the echo. You see, oh geez, they have a paricardial fusion. They got cardiac tampon. What do I do? Paricardioentesis. That's going to be the best way in a patient who is unstable, right? And it's going to be diagnostic and it's going to be therapeutic. We talked about that. But in a patient who has malignant paricardial eusions that keep forming recurrently that puts them at risk of cardiac tampenade, we need a more permanent solution. And that's where a paricardial window will come into play. Right. But again, just paying homage to 2:34:32 the paricardioentesis. You can tap in subzyoid. You can tap in in the paristernal. You can tap in apically. Either way, these are going to be quick fixes. We need the long-term fix. What's that going to be? We got to basically create a window between the paricardial cavity and somewhere where this fluid can drain. And that's where we'll do a paricardial window. We'll kind of open it up and allow for that fluid to drain maybe into the parrot's name in this case. So that we don't keep dumping that allowing that fluid to just accumulate and accumulate in the paricardial cavity. increasing that stretch beyond that limit. Boom. We can't stretch anymore. Start smashing and squeezing on the heart like an accordion. And that's where you're going to get cardiac tampenon. All right. Woo baby. That was a long lecture. I'm really sorry. I know that sometimes these lectures can be really long. I think we try to focus on learning, understanding, making sense of things, having fun, um to make learning more enjoyable because I know it can be tough sometimes as a student. I've been there and I'm there for you all. I love you all. I really hope that at the end of 2:35:29 this you feel more confident. You feel like you got you know you got something out of this and um I just really thank you guys for being such amazing supporters for always sticking with us and I really wish you all the absolute best and I truly mean that from the bottom of my heart. So thank you guys so much. I hope you learned a lot. Love you. Thank you. And as always until next time my friends [Music]
