DIP Episode 481 - The Clutch Inclusion Bodies Podcast (for Step 1-3)

Welcome, my name is Divine. This is episode 481 of the Divine Intervention Podcasts. And into this podcast we're going to be going over inclusion bodies. So let's call this the clutch inclusion body podcast. Now personally, I tell people this. With these inclusion bodies a lot of the time, the thing that makes the most important sense to know is the clinical presentation. Most times on your USMEL exams, you're going to be getting these questions right by clinical presentation. So many of them, honestly, trying to memorize how they look on histology in my experience is not a particularly high-eal activity. Most times you get more bang for your buck by knowing how to identify these things, I mean, from a clinical perspective. But at the same time, I am also going to talk about some unique features that you may see on histology. So I'll encourage you as you listen to this podcast or after you listen to this podcast, whip up some Google and do some searching. But again, I kid you not. Most times is the clinical presentation that's going to be your helpful fact here. Okay, so let's begin. So what do they give you a question about a 65-year-old man? And they tell you that for the past few months, he has had a lot of slowing of his movements. And they tell you that he has a lot of tremors and whatnot. Well, if you see something like this, I would really hope you're thinking about Parkinson's disease.

Now remember, Parkinson's disease, the primary place that's affected is the substantial Niagara. So these people obviously have very low levels of dopamine. So the substantial Niagara is affected, so they don't have adequate amounts of dopamine. That's why if you notice, it makes sense that many of the Parkinson's drugs, they just stimulate dopamine receptors. So things like bromocryptin or carburegoline, or they increase the release of dopamine in the central nervous system like a mantidine, or you're giving them straight-up dopamine, like carbidopa, levodopa. Or you're giving them things that inhibit the breakdown of dopamine, things like intacapone or tucapone or selegelin or acagellin. So what's the big thing you want to know about the inclusions you're going to see in Parkinson's disease? Well, the critical thing to know that you're going to see is you're going to see inclusions of alpha-synuclein. You're going to see Louis bodies. That's the term. You're going to see Louis bodies. But the thing is, I've noticed that many times with these inclusion bodies, one thing they love you to know is, where do we find them? Although that doesn't always matter, but many times it does. What are these things made of? And what are the disease processes that relate to these things? So you're going to see Louis bodies. These Louis bodies, they're going to be made of alpha-synuclein. Alpha-synuclein. Alpha-synuclein.

And the thing is, you may wonder, what in the world does alpha-synuclein do? Well, alpha-synuclein is actually involved in double-stranded DNA-breaker repair. So the thing is, when you have this mutated alpha-synuclein in people that have, like, these Louis bodies, they're going to have essentially mis-folded proteins. And these things can trigger cell death. So if you think about if a lot of cells begin to die, that's probably not a good thing. That's probably not a good thing. That's probably not a good thing. So again, people that have these mutated alpha-synucleins, they're going to have issues with DNA-double-stranded breaker repair. Remember, if you cannot repair DNA-double-stranded breaks very well, then you're going to have an increased risk of, like, cells dying and whatnot. And that's obviously not a good thing. And remember, these Louis bodies, we don't only find them in Parkinson's disease. We also find them in Louis body dementia. In fact, we find them in some of these Parkinson's plus syndrome. Like a Parkinsonian variant, something known as multiple system atrophy. We tend to find Louis bodies in that as well. Again, remember, mis-folded proteins can cause a lot of problems. In fact, let's make a few integrations here on mis-folded proteins. I just said that, oh, this alpha-synuclein issue many times, it's a mis-folded protein issue. Or think about it. When people have alpha-synanti-tripsin deficiency, believe it or not, it's also a mis-folded protein issue.

It is also a mis-folded protein issue. So those mis-folded proteins, they're going to accumulate in the liver. They're going to start causing death of the liver cells. That's one of the reasons why people that have alpha-synanti-tripsin deficiency, they're going to liver failure. If you also look in terms of mis-folded proteins, think of a lot of amyloidosis. A lot of amyloid, basically, you have, like, some bad proteins, some of them are mis-folded. They aggregate together and form amyloid, and then you run into a bunch of problems. Now, what if they give you a question about a person that is, like, 47 years old, and this person has started having weird behavior, started seeing things that are inappropriate, putting things in their mouth, just having very disinhibited behavior. If you see something like this, what should you pick as your diagnosis on an exam? Here's the thing. The USML is very smart. Otherwise, USML examinerator do option A, haunting tense disease, option B, frontal temporal dementia. Because by putting that agent of 40s, they know that some people's minds will almost like reflexively think to haunting tense disease. But don't be haunting tense disease. Hunting tense disease, they're going to give you predominantly the core form movement. They're going to have a lot of core form movements. You won't see disinhibited behavior as the predominant feature. So, people that have haunting tense can have some disinhibited behavior.

But people that have frontal temporal dementia, they have a lot of disinhibited behavior, seeing inappropriate things, acting inappropriate ways. Believe it or not, frontal temporal dementia, which we call pick disease, is actually the most common cause of early onset dementia. That's actually a very high yield to know. It is the most common cause of early onset dementia. Many times people that have picked disease, they usually have between age 40. The onset is usually between ages 45 to 65. Typically, these people, what's the clinical inclusion you're going to see? We're going to see pick bodies. What are these pick bodies? These pick bodies, they're basically a bunch of hyperfossilated tau proteins. Hyperfossilated tau proteins. That's probably about as much as you need to know for frontal temporal dementia. What if you give you a question about a person that's in their 40s and their 50s? You see them over the last few months. They started having trouble using their hands, they tell you that they have a positive Babinsky sign, they tell you that they have some muscle atrophy, and it's doing different muscle groups and whatnot. When you see them, they also have hyperreflexion of the extremities. If you see something like this, I really hope you're saying, oh, divine, this sounds a lot like ALS, right? E-myotrophic lateral sclerosis. Remember, in ALS, people that have ALS, they have problems with both upper motor neurons and lower motor neurons.

It's a motor neuron disease, both upper and lower motor neurons. So you're going to see upper motor neuron symptoms. You're going to see lower motor neuron symptoms. What are you going to see as the inclusion? In fact, if they give you a question and they tell you that, oh, you see an inclusion with the motor neurons. But again, you see the appropriate clinical context as I've described. Think of ALS. These inclusions are known as Boninna, but it's BU-NI-NA. B-U-NI-NA, buddies. So these buddies are made of SOD1, right? So of them are made of TDP43. Again, believe it or not, I know some of these things may be like, man, the fine distance looks like real oiled stuff. Once you then see them on the exam, even step-toe step-toe step-toe, and you're like, wait, what? So again, it's just important to kind of know these things. So these things, the inclusions, they accumulate within the cytoplasmic inclusions, they accumulate within motor neurons. That's the critical thing to know. And again, they're part of the pathophys behind a mitrophic lateral sclerosis. Now, what if they give you a question about a patient? And they tell you that this patient is European. And this person has had a very significant anemia, and it's been found in many family members in the Rosydecanemia. And that this person got a procedure like a year or two ago. And then they ask you, what do you expect to find on a blood smear?

And you're like, oh, divine, this sounds like hairdresser's ferocious cytosis, which it is. And you notice that sphero site conspicuously is not one of the answers. And then you're like, man, which are so bright-pick. I really hope you're saying, let me pick the answer that says, how are jolly buddies? You're like, wait, what? Divine. How do you think jump from hairdresser's cytosis to how are jolly buddies? Well, let me explain. Here's the thing. The thing is, one of the ways you treat hairdresser's cytosis is what's reflected. Because remember, in hairdresser's cytosis, there's more dominant disorder, spectra and anchoring, and some band proteins I'm using. Those are riblocell membrane proteins. They don't work very great. So since they don't work great, the riblocell is very small. It's very, very small. So because it's very, very small, you know, it doesn't look like a normal red cell, looks like a spherocyte. The splinic macrophages don't like that very much. So the thing they do is they pretty much damage those cells. That's how you get the himalosis. So many times for these people, one of the ways you can treat a disorder is by doing a splinectomy. Basically, when you do a splinectomy, surprisingly, those splinic macrophages go out of the way. They go out of the way. And you stop killing these perfectly good, but a little abnormal spherocyte. So if you don't splinectomy though, obviously, you're going to start having how jolly buddies.

So maybe I think it may be helpful to think about what's a how jolly buddy. Basically, how jolly buddy is a nuclear remnant of a riblocell. We know that riblocells in the terminal form go in container nucleus. Many times before they won't leave the bone marrow, many of those nuclear elements are removed. But sometimes it's not. Sometimes you still see some remnants. So those remnants are removed by a splinic, they are basically filtered out by the spleen. They are pretty much filtered out by a healthy spleen. But if you don't have a healthy spleen, because you either don't have it, because you've had a splinectomy, or you see a person that has sickle cell disease, because remember, people that have sickle cell disease, they essentially undergo an all-use plenectomy, they essentially infarcts their spines and pretty much over lutes over time. That can basically take that spleen out of the equation. And that can cause those people to have how jolly buddies. Again, remember, it's a nuclear remnant. Now, how do you identify a how jolly buddy? The thing is, is something you can see on a regular H&E stain. A regular H&E, my toxin and Eosin stain. And it's going to be like one, it's basically going to be one single, like blow a purple spot. Okay? It's going to be single many times on your exams. But again, as I said, don't just use the picture alone. They're going to give you a clinical presentation.

The USM Lists can not just write a question and just throw a picture and throw like zero context. Again, that's one thing I try to really emphasize to people. You're going to do much better on the USML exams by knowing context, not just memorizing random details. If you've ever attended any of my classes, you'll see that the USM Lists can't just write a question and you'll see that almost all my classes pretty much have context, clinical presentations. Because that's the way your real exam is going to look like. And by the way, if you're taking any of your exams, soon, I have a bunch of classes that may help you. I'm studying on Thursday. Actually, Thursday, Friday, Saturday, I have classes that are applicable to step one or the way to step three. I have a test taking class on Friday, 20,5 hours. I mean, on Thursday, 20,5 hours, I have a bio-stats class, 4 hours, on Friday. Then I have a five-hour social sciences, quality improvement, and ethics class, and health care systems class on Saturday. These are applied to step one or step three. The next week from Monday to Saturday, I have a step one class, it's 25 hours, it won't be mid- or Wednesday, but again, it's all over Zoom. And also the class is also helpful for people that are taking step two or step three, and have very poor step one foundation. Let's see, it's filled in step one exam. Maybe a good class for you to take. And then the week after that, I have a step two or step three classes, a 20-hour class.

And the main people are taking these classes and finding it to be profoundly helpful. So if you're interested, just shoot me an email, and I can give you some more information. Okay, so let's continue right here. So again, how do you all do this? Again, you're going to be a single blue spot, a single purple spot. And again, you don't need to stain the red blood cells especially to see them. Most histology images, you're going to see on your exams, or H&E stains, in my talks, in an EOSM. There's nothing particularly special in terms of staining with these stains. You don't need a special stain. So the EOSM is many times, we'll not mention a special stain. And you're still going to be able to see how jolly, but again, remember, it's not only in sickle cell disease, you're going to see this stuff. You can also see this in a person that has had us connect to me. Let's say, so there are many different ways they can test this. Again, remember the EOSM is, what they love to do a lot of these days is, is the same classic stuff they've always tested at the test. But they just find unusual ways to test that classic thing. Because many times we'll think that they just invent all these new concepts. No, that's not really true. They're just taking the same old concepts, just finding more inventive ways of testing them. So you can see like this, how jolly body question went over. Literally, I went over it in the context of a person that had been treated for heterotusitis.

But believe it or not, you can also see the same kind of question. And a person that has been treated for immune thrombocytopenia, because remember, it's preneptomy, is a third-line treatment treatment measure for ITP. Or they can give you a question about a person that had mono, right, towards in contacts, or dealing with it into their physician, had like acute abdominal pain that resolved over time. But if pretty much ruptured, they're splints, right? Believe it or not, even people that have like really bad splints from some kind of like hematologic malignancy, they can also have how jolly bodies. Basically, if you're splitting those in function right, you can potentially have how jolly bodies. Okay, now what if they give you a question about a patient? And you tell you that this guy, he's like a 32-year-old male. And for the past like three months, he's been having a lot of abdominal pain, a detailed physical exam, he has like a restrile food drop. How's all this peripheral neuropathy? And then they tell you that the person's hemoglobin is 8.2, and the person's MCV is 71. Well, if you see something like this, I'll really hope you're saying, oh, divine. This sounds an awful lot like lead poisoning. They're like, wait, what? Lead poisoning? Yeah, lead poisoning. So how do they like to test lead poisoning on the exams? Well, the USM is the love to give people to have lead poisoning by Corsitic anemia. That's one, two, they're gonna have abdominal issues.

Many times they're gonna have abdominal pain. Number three, they're gonna have peripheral neuropathy. And not saying they're always giving you all those things, but those are classic signs and features of lead poisoning, of lead poisoning. So what's gonna be the intracellular inclusion, you're gonna see in a person that has lead poisoning? Well, the thing you're gonna see is you're gonna see Bysophilic stiplin. You're gonna see Bysophilic stiplin. Basically, these Bysophilic stipples are made of RNA, just like ribosomes, basically. Ribosomes, basically. Essentially, whenever you see Bysophilic stippling, think of screwed up erythropoices. Think of screwed up erythropoices. Right? So how does lead scrub erythropoices? Well, it's gonna do that by basically inhibiting ferroquilities and eally dehydrates. Those are two enzymes that are necessary for hymnsynthesis. So those two enzymes when they get screwed up, you're gonna have erythropoices problems. Again, they wonder like, why does this happen? So you can get this Bysophilic stippling because lead pretty much inhibits the degradation of ribosomal RNA. And if you inhibit the degradation of ribosomal RNA, then that can certainly cause those things to accumulate. So that's how you get those Bysophilic stepples. Please don't confuse, and maybe before I jump into another thing, let me see something about Bysophilic stippling.

One thing that's gonna help you know that oh, I'm doing Bysophilic stippling is you're gonna see multiple dots in the ribosomal RNA. Many times they're like blue. They look like blue. So like multiple blue dots throughout the ribosomal RNA. Multiple blue dots throughout the ribosomal RNA. That tells you that, oh, wait, this is very likely Bysophilic stippling. And please don't confuse Bysophilic stippling with a ring-sideroblast. A ring-sideroblast is also something you're gonna see in lead poisoning. But how does that happen? Remember, lead inhibits ferroquilities. What does ferroquilities do? Ferroquilities basically takes iron and protopry and combines them together to make him. And also, lead as we know, inhibits ailey dehydrates. Ailey dehydrates is more upstream in the synthesis of protopry. So essentially, iron is available, but protopryne is not being made. Because again, you have an upstream inhibition and a downstream inhibition. Upstream your inhibiting ailey dehydrates. Downstream your inhibiting ferroquilities. So you don't need protopryne at all, because you literally need ailey dehydrates to make protopryne. So if you don't make protopryne, iron is just gonna be standing around, saying, wow. Okay, protopryne, it's waiting time. Where are you? But protopryne doesn't show because lead is shutting everything down. So iron will just pretty much hang around the mitochondria.

That iron hanging around the mitochondria is what forms a ringed cedar blast that we see in lead poisoning. Now, remember, rings cedar blasts are only seen in lead poisoning. We also see them in my ludisplastic syndrome. So again, just something I wanna keep in mind. But many times lead poisoning is the big area you're gonna find out of one of the exams. So again, because with a philix dipole, you're gonna see multiple blue dots. Now, another thing you may see with lead poisoning that I guess may be helpful to identify are these Papandheimer bodies. I think you spelled as PA, WP, EN, HE, IMAR, Papandheimer bodies. They are pretty much iron inclusions. That's actually pretty high autonome. They are iron made, right? They're essentially inclusions of ferritin. So you may wonder, man, how do I differentiate this thing from philix dipole? I said that philix dipole, you're gonna see multiple blue dots throughout the red blood cell. Well, Papandheimer bodies, you're gonna see like one, two, or three blue dots. I mean, in times it's gonna be periferial in the red blood cell. It's gonna be like eccentric. It's gonna be periferial in the cell. It's not gonna be distributed throughout the red blood cell. I don't mean be something that I think will probably help you on the exam. So again, let's just kinda summarize real quick. How do you really bodies? You're gonna see a single blue big dot, right? Philix dipole, you're gonna see multiple dots kinda throughout the red blood cell.

Papandheimer bodies, you're gonna see like one, two, or three dots. Sometimes it can be a little more than three, but you're gonna be periferially located. Okay? It can be periferially located. Many times you're gonna see more than one dot on your exam. But again, please don't just be relying on these dots, also relying on the clinical context, right? And again, maybe just to throw in one integration that I think can really break open some people's understanding. Because I know put a listen to this podcast they largely wanna try to really understand what's going on. I just said that C, that lead, essentially inhibits protoproferin synthesis, right? And iron is available, but iron is just not, doesn't have any marriage partner to form him with. So iron just builds up, builds up, builds up. So believe it or not, lead poisoning, iron are going lead. So people that have lead poisoning, what do you think is trophy a ferritin? The ferritin is actually pretty high. I will not be surprised if this really high ferritin is what then ultimately leads to this ferritin just clumping, clumping, clumping within the cell and forming these pop-in-himer bodies. That's just a presupposition. But pop-in-himer bodies for sure, I made a ferritin. Just maybe something that may help you remember that pretty well. Remember ferritin is high in lead poisoning. That's actually quite unusual in micro-city canemias.

Although sometimes anemia of chronic disease can cause micro-city canemia your ferritin will be high because of the hip-sidine business. I've talked about that in many podcasts in the past, right? But in general, iron deficiency anemia your ferritin is pretty low. But in lead poisoning your ferritin is pretty high. So that's kind of explained why because iron acumulates because it doesn't have any peripheral freinage partner. Just a nice way to remember that. Now, what do you think of your question about a person? And you tell you that the person recently took like a dapsone for some stuff. Remember, you can use dapsone for things like I think I use it for this thing we find in Celiac disease dermatitis or proteformis. You can also use it for some stuff in HIV. And you can also use it to trick leprosy actually. I think leprosy is treated with a combination of dapsone, or a frontin and clophazamine. I remember it with DRC, dapsone or a frontin, clophazamine. I think you have to take it for like two years or something like that. That's a trick leprosy. And I think the HIV angle and dapsone I believe goes with animosistis-dravetsi. Again, these are all things you can look up that's not the focus of this podcast. But it's a very powerful oxidant. We see a person that has recently taken father beans. And then now they're having like a fondle-puller, they have inshotness of breath, they have anemia. Obviously this is going to be a person that has a person that has g6pd deficiency.

Again, remember women cannot get g6pd deficiency on your exams. Because as it so happens, it's an excellent, recessive disorder. So it's going to be almost exclusively males on your test. Now, what are you going to find in g6pd deficiency? Well, on a blusmer you're going to see hyens bodies. These hyens bodies are just dematured hemoglobin. Because if you think about it, g6pd is part of the critical enzyme. In fact, it's the real-metre enzyme of the oxidative phase of the pentose phosphate pathway. Glucosex phosphate dehydrogenase. It helps you make any DPH. Any DPH helps you regenerate your glutathione. So you can deal with oxidative stress in a red blood cell. Because think about your red blood cell kind of carries oxygen. Oxygen is good for a rose, but it's kind of dangerous too. It's kind of toxic and all these things. So all that oxygen, because red blood cells, that in people that have g6pd deficiency, another thing you would make any DPH, the problem you're going to run into is that the Fe2 plus in the red blood cell, that's the fair cyan, it's going to be oxidized to a fairychir, that's Fe3 plus. Another Fe3 plus, right? If it's in that state, the hemoglobin is going to be dematured. So that dematured hemoglobin is what forms a hind's body. That dematured hemoglobin is what forms a hind's body. Now here's the critical thing. You cannot see hind's bodies on a H&E stain. You need to stain the red blood cell specifically to see a hind's body.

So typically, you're going to use something known as the supervidal stain, the supervidal stain, the supervidal stain. So the red blood cell is not going to look like a regular H&E stain red blood cell. You're going to see a red blood cell that looks very well stained. One thing I would just say is, you almost will not be able to pick out hind's bodies without an appropriate clinical presentation, like a present that has g6pd deficiency, or they give you a father-been business, or they give you something about taking a very powerfully oxidized drug, like DAPSON or Primer Quake, for example. When you see something like that, think of hind's bodies. And then those red blood cells that contain hind's bodies, when they literally get to the spleen, the spleen macrophages will literally take a bite of those hind's bodies out of the red blood cells. You're going to find from these bite-bites cells. So again, hind's bodies are very almost impossible to differentiate from many of the other things, many of these other inclusions. But again, like I said, if you see the work supervidal stain, they're pretty much telling you that, oh wait, this is a hind's body. But again, I'm telling you, like 99% of the time, you're probably going to get the answer right, by just looking at the clinical context and presentation that is given to you. Okay, now let's go ahead and wrap this up. Just a few more quick things I'm going to go over here.

I remember if you see a person that has anemia, they have fever, they just went to some foreign country, and they just came back, they can make this a military question. And they show you all these inclusions that look like bananas within red blood cells. Obviously, there's going to be malaria, right? Plus, plus, plus more, more problems. Okay, and then what if you see a person that also has, he has, he has like, he molasses, has fever, you notice that the endorebular ribin is up, and they've just visited the New England area, and you'll see a red blood cell, you know, you see fever, see all these things, right? I think about these uses, right? Babesia, Babesia might grow, remember, you're going to see this multi-scross pattern. Remember, Babesia is carried by the exodistake. The exodistake carries an plasma, carries Babesia, and carries a Borrelia Bocdofer. That's pretty, pretty high autonope. Remember, Babesiosus causes an anemia. Okay, causes an anemia. You're going to see that multi-scross pattern. Basically, you're going to see a cross in a red blood cell. Okay, now, what if they give you a question about, actually, there are many ways they can test the same concept. They can either give you a newborn that has parabenitricular calcifications on brain imaging.

They can have microcephaly, they can have hearing loss, usually, of the sensory neuro-variety, or they can give you a question about a HIV person that has eye problems, right, like red nitase, or they can give you, like, some post-transplant patient that has, like, a bloody diarrhea and all these things. Right? And then, they show you, like, something that looks, you see a nucleus that looks like an outside. Right? An outside nucleus. Right? That's going to be CMV. These are all the different ways they can test CMV on your, on your exacts, right? They can test the outside nucleus. Basically, you're going to see, like, a lot of, like, almost like a dark blue, and you're going to see, like, white around it, a perinuclear halo. Believe it or not, that can be the term they use, right? They can say, oh, biopsy of blah, blah, blah, blah, blah, shows you cells with a, with, you know, nucleus that has a perinuclear halo. That perinuclear halo is just them choosing to not see outside nucleus. So just be careful. You can remember the USML is the love derivatives. It's also saying outside nucleus, they can just call it a perinuclear halo. When you see that, think of CMV. Remember, CMV, we're going to manage that with GANS-Cyclovir. We gung up on CMV with GANS-Cyclovir. Obviously, GANS-Cyclovir does not work. We're going to go ahead and try out for false carnage. That's the pyrophospheda, I know. Okay. Now, what do they give you?

A question about a person that comes to the emergency room, and the person who's for the last is, like, a 60-year-old man. And for the last two hours, he has been bleeding from his nose, bleeding from his ears. And then they tell you, you know, you get, you get labs like a CBCU. Notice the person has, like, a really nasty anemia. And the person has a really nasty thrombocytopenia. But their white blood cell count is elevated. And then they show you, like, a white blood cell, like a blood cell. And you see this long stuff inside it. And when you see stuff like that, I want you to think of an outer rod, this person clearly has a Cucromylocytic leukemia. It's a cytoplasmic inclusion, where we tend to find it within these myloyblast cells. And what does an outer rod contain? An outer rod contains lysosomes and lysosomal enzymes. They look like sticks. This is something you absolutely need to be able to identify when you examine. So what's the path of this behind a Cucromylocytic leukemia? Well, you have this 15-17 translocation. You have this 15-17 translocation. And then you have this problem. And when you have this translocation, it's going to prevent those blood cells from maturing father. It's going to prevent them from maturing father. So they're going to be stock as blast cells. That's how you get these things. And the thing is, these blast cells, they are big and bulky. So they take up a lot of space in the bone marrow.

So making other blood elements is not going to be very efficient with those blast cells that are just getting big and beefy, big and beefy, big and beefy. So you may wonder, why does acupromylocyc leukemia present like this? Well, this person that I just described has a DIC. So again, they can even give you an acupromylocyc leukemia question and give you a bunch of hours as your answers. Where you ask you for things like platelet count, PT-PTT, D-Dimers, Fibrid Negotiation products, and things like that. Make sure you can do those things. Obviously, if you have DIC, your platelet count is going to be decreased. Your D-Dimers are going to be elevated. Your PT-PTT are both going to be elevated. Your bleeding time is going to be elevated. Can you just see the way the USMD is? They are just so many things they can test for just seemingly mundane pathologies. So that can be just like a unique novel way to test acupromylocyc leukemia. They know that, oh, you know the hour or you've memorized all that stuff. Find no problem. But you can just choose to say, you know what? Let's do this fancy shmanse fan of trying to see if you can pick out DIC labs for an acupromylocyc leukemia question. So why does acupromylocyc leukemia, though, cause the IC? Why does it do that? Well, the reason is that these blood cells, these leukemic cells, and acupromylocyc leukemia, they actually contain pro-coagulant granules. They contain pro-coagulant granules.

Remember, why do cell have a ton of granules in them? So these pro-coagulant granules, they can actually trigger the coagulation cascade. And this is actually pretty instructive. This is why when people have acupromylocyc leukemia, we don't give them traditional chemotherapy. Because if you think about it, many chemo drops, they cause lysis of cancer cells. They cause the lysis of cancer cells. Well, here's the problem with acupromylocyc leukemia. If you like those cancer cells, I wish you all the best, because guess what? You're going to be releasing all these pro-coagulant granules into the circulation. You're going to trigger the coagulation cascade, you're going to give the person DIC, then they're going to die. You don't want that. So how do we treat acupromylocyc leukemia? Well, we're going to use all trans-retinoic acid. We're going to use atra, all trans-retinoic acid. What does all trans-retinoic acid do? Well, basically what it does is, it converts the blast cell to a neutral field. It pretty much causes, though, it doesn't explode the cells. No, it doesn't do any of that. Because excluding the cell is not what we want, but only gives the person DIC and kills them. What happens is, it's going to overcome that maturation block. You get from the 15-17 translocation, and then you're going to form neutral fields. Neutral fields generally don't divide any further.

So since they cannot really divide much, you've pretty much cured the malignancy after that, because you're differentiating the blast cell to a terminal cell that will die off, and then the person is going to be fine. Again, I'm not saying neutral fields can never divide again. But atra basically causes a terminal differentiation of those blast cells. So the cancer will stop propagating essentially. And then the last thing I'm just going to talk about here is don't forget your bar bodies, bar bodies kind of matter. Although they are things that matter more for step one. It's pretty much an inactivated X chromosome. Females should have one bar body. Because remember females have 46 XX. So they should have only one, they should have one bar body. But why me, you find a bar body in a male on your exam? So it's going to be Kleinfelter Syndrome. Remember Kleinfelter. Kleinfelter, people that have Kleinfelter are, you know, XXY. They're going to have, because most males are 46 XXY, but they would have Kleinfelter, they're like 47 XXY. So they have two X chromosomes. So one has to be inactivated. That's a bar body. So if you see a bar body on a chirootype, usually they're going to test bar bodies in the context of chirootypes. You see a bar body on a chirootype in a male? I want you to think of Kleinfelter Syndrome straight up. People that have turned their syndrome remember those people are 45 X.O. They only have one X chromosome. Generally, they shouldn't have bar bodies.

And how do you get bar bodies? How do you inactivate these X chromosomes? Well, you're going to inactivate them by a process known as lionization. You may be like lionization. If I'm please spell that for me. Yeah, I'm going to spell this. L-Y-O-N-I-Z-A-T-I-O-N lionization. Basically, it's just something I want to recognize for a step one. You may see it on your exam and be like, whoa, where's this word? Well, now you know. And how do you inactivate these X chromosomes? Well, you're going to do methylation. Remember, whenever you methylate his stones, we methylate DNA, especially at like CPG islands, these CPG sites, you know, cytosine and guaninsite, is going to cause the DNA to pretty much shut down. It's not going to be transcribed as regularly. So that's something you just want to make sure that you know. Now, one weird association you also want to know with bar bodies is that bar bodies are much fewer in breast cancer cells. Because if you think about it, right? And that should sort of make some sense. Because when people have cancer, right? You have like uncontrolled cell proliferation. So it would make sense that you don't want to be inactivating your chromosomes. You want them to be like heavily, mightily, majorly expressed. So breast cancer has an association with breast cancer cells. Have an association or having fewer bar bodies than his brain. Okay. So again, I think I'm going to go ahead and stop here. There are other inclusion bodies I did not discuss.

But those ones have discussed many different podcasts. And those are ones where like, honestly, context is what matters. Things like phariginous bodies, in asbestosis, contrary type A bodies and what not. And all those things. Those things are just more better discussed from a clinical context. Honestly, these are the ones that I will say that clinical context is where you're leading to be focusing your energies. But trying to just memorize a bunch of histology images. Okay. So I'm going to stop here. Again, I offer one or one to learn for step one to step three and med school exams, including shelf exams. I help with era's applications, personal statements, reclators, walk interviews. I can have review classes for step one or the week of step three. I have these podcasts on the major apps Apple Google and Spotify. I have a You Tube channel, Divine Intervention, USMD podcast and videos. That's where I post the videos that I make. And then finally, I have a new website called Divine Interventional Lifelessens.com. In fact, there is an Apple podcast associated with it called the Divine Interventional Life Lessons podcast. Many people have said that, oh, Divine, I love your life lessons. So what did I do? I made a separate website. And pretty much every week, I would very few exceptions. I post two new podcasts from a biblical perspective and address a life lesson. Many times, they are like 10 to 20 minutes long. I should have tried to put them up on Fridays and Sundays.

So just listen to those. I think you'll find those to be pretty helpful. I think they have more than 210 of those podcasts at this point. Okay. So thank you for joining me today. I'll see you in episode 482. Have a wonderful rest of your day. God bless you. Bye for now. Thank you.

Alpha-synuclein.

FTD presents with disinhibited behavior and behavioral changes, whereas HD predominantly shows chorea/core-form movements.

Pick bodies.

Splenic dysfunction (e.g., splenectomy, sickle cell crisis).

Basophilic stippling (multiple blue dots throughout the red blood cell cytoplasm).

Supervidal stain (or similar specialized RBC stain), as they are denatured hemoglobin.

Alpha-synuclein; Parkinson's disease (and related synucleinopathies).

Amyotrophic Lateral Sclerosis (ALS).

Nuclear remnants; Accumulation occurs due to impaired splenic filtration/function.

Lead inhibits ferrochelatase and ALAD, preventing protoporphyrin synthesis, leading to the accumulation of ribosomal RNA (blue dots).

Pappenheimer bodies are peripheral iron deposits (1-3 dots); Basophilic stippling involves multiple blue dots distributed throughout the entire red blood cell cytoplasm.

G6 PD deficiency; Diagnosis requires a strong oxidative trigger (e.g., fava beans, certain drugs) and specialized staining.

Alpha-synuclein; Parkinson's disease (and related synucleinopathies).

Amyotrophic Lateral Sclerosis (ALS).

Nuclear remnants; Accumulation occurs due to impaired splenic filtration/function.

Lead inhibits ferrochelatase and ALAD, preventing protoporphyrin synthesis, leading to the accumulation of ribosomal RNA (blue dots).

Pappenheimer bodies are peripheral iron deposits (1-3 dots); Basophilic stippling involves multiple blue dots distributed throughout the entire red blood cell cytoplasm.

G6 PD deficiency; Diagnosis requires a strong oxidative trigger (e.g., fava beans, certain drugs) and specialized staining.