DIP Episode 507 - The Clutch Sickle Cell Disease Podcast (for Step 1-3) Part 1

Welcome, this is episode 507 of the Divine Intervention Podcasts. To these podcasts, I'm going to be addressing sickle cell disease. I'm going to call this the Super High Yield Sickle Cell Disease Podcast. This podcast is extremely high yield and I know it's going to be about sickle cell disease. But there are so many integrations I'm going to make with so many disciplines. It's worth your while living if you don't care to learn about sickle cell disease or you feel like you know every single thing about sickle cell disease. And again, the way I'm going to introduce this is I'm going to give some background and then I'm going to start releasing some vignettes as we go along. And honestly as I release these vignettes, right, again you'll just see me say, what if they ask you this, what if they ask you this? You'll kind of be very informal, but again if you really pay attention here, you can get a ton from this. Now, really try to see if I can feed this into one podcast, but if I cannot, I'm just going to make it in a makeup part too. But honestly, there's a very, very, very high yield podcast. Okay, please just make sure you know the stuff. Okay, so sickle cell disease, we know the classic demographic that gets this, right? It's almost always going to be an African's on the USMID exam. So there's going to be something that I'm going to see in Africans, right?

But just be careful though, you may also see this in people that are Hispanic, people that are of Mediterranean ancestry, so people from like Italy, from Libya, stuff like that, people that are Asian, right? And Indians, believe it or not, Asians and Indians can also have sickle cell disease. Asians and Indians can also have sickle cell disease, right? So what causes sickle cell? Well, it's pretty much a single base change, right? Basically in the beta globing gene, you substitute a glutamic acid for veiling. So normally, glutamic acid is supposed to be at that position six. But then you're like, okay, well, because of some generic mutation, the glutamic acid gets swapped out and you put veiling instead. When that happens, that's a problem. And the genetic mutation, because you may wonder like, why is it a sickle cell disease? Because there's so many problems. Here's the thing, right? It's kind of a subtle point, but it's actually a very important point to keep in mind. So whenever you have hemoglobin that has had that glutamic acid swap out of veiling, we call it hemoglobin S. We literally call it hemoglobin S. Now, whenever you have hemoglobin that contains hemoglobin S, and you see that in both copies, because remember where we're deployed organisms, right? So, because you know, people can have sickle cell trigrate, they have one hemoglobin S, and one no more hemoglobin, that's hemoglobin A.

But if both copies, if both copies, right, you're homozygous for the problem, if you have both copies, then that's an issue. So you're hemoglobin SS. So what's the underlying pathophys behind many of their symptoms? Here's the thing. First, you need the perfect condition. The perfect condition is the oxygen-ethyth tissue. Okay? The oxygen-ethyth tissue. Whenever you're in a region of the body, where there's not a ton of oxygen, those hemoglobin SS, they love to polymerize. They love to come together. Hypoxia is like the perfect marriage for them. It's like the perfect, perfect, perfect storm for them. So they come together, they form these polymers, and as they form these polymers, problems arise, right? Because when they form these polymers, because remember, hemoglobin is a big chunk of what is an array blood cell. So when these hemoglobin SS polymers, they come to, when you form these polymers, the red blood cells begin to sickle, right? And those sickle red cells, they have a few bad properties. Number one, they don't flow as fast. So they basically make your blood flow slow. And when your blood flows slowly, think about it. You probably remember Verkho's triads. Stasis hypercogulability, and then the cellular dysfunction. Your blood is flowing slowly. You have bloodstasis. You have a higher risk of venous trombone molyc disease. That's one. Number two, those sickle cells, they love to occlude vessels, right?

Because that shape is just abnormal for the contours of most of your blood vessels. So they can occude blood vessels, and they can cause ischemia of tissue. And that can cause tissue dysfunction, it can cause tissue death. The third problem with these sickle cells is that they are especially prone to hemoluses. They love to explode. They are very, very, very prone to hemoluses. So again, these sickle cells, one of the three problems. Number one, the flow slow, that bloodstasis can raise your risk of hypercoglable problems. Number two, they explode very easily. They are very prone to hemoluses. And number three, the occlude blood vessels. If your contours are not great, so the occlude blood vessels, they cause ischemia of all these problems. And really, you know, I'm sure many of you are aware of many of the classic sickle cell problems. Like the acute pain crises, many of you will have chronic pain. They tend to have a lot of organ problems. So you're just going to keep that at the back of your mind as we kind of go through these things. As we kind of go through these things. Now, let me see if I can make some integrations here. So let's say they give you a question about a patient. And they tell you that, this person has sickle cell trait, and his wife has sickle cell trait. And then they say that the parents request pre-conception canceling. And then you explain to them that, oh, see, and they will make these questions super, super long.

They tell you that, oh, see, you know what? If you have a, since both of you have the trait, you have like a one in four channels of your child having sickle cell disease, which makes sense, right? Again, remember sickle cell disease, kind of like autozone recessive, right? So if you do the ponet square, if you cross things properly, you'll see that, wow, if mom is a carrier, that's a carrier, if you cross everything, there's one permutation of the four permutations you get that give you SS, right? So they can then ask you, you may be like, wow, this is a sickle cell question, okay, this looks easy. And then they ask you, by offering or by conducting pre-conception canceling, what kind of prevention, what kind of preventive medicine strategy is being employed by the physician? Right? I will hope you're saying, oh, divine, I want to pick the answer that says primary prevention. Hmm, right? So again, what is primary prevention then? Primary prevention again is when you do something to prevent the development of disease in the first place, right? So see for example, right? You're doing pre-conception canceling. You're trying to speak to these parents about the risk of having a child that may have sickle cell disease. So the disease has not happened in any of their offspring. You're trying to like talk with them to prevent that issue from happening in the first place. That's an example of primary prevention. That's an example of primary prevention, right?

That's an example of primary prevention. Now, one of the, because again, the US NL is these days, I kid you know, they're just kind of very good at these in, like I like to call them in no-course questions. You're like, where is this coming from? You just see how they take something. I really do something that you would not ever imagine in a thousand years that they'll be able to make those kinds of correlations. So you should something you want to keep at the back of your mind. Okay. Now, what are some other high old things to keep in mind with sickle cell disease? Well, we know that there are so many things. But again, I want to, let me lay the background for us. Just brought over view. And then I start going into a little bit of detail, right? But remember, people that have sickle cell disease, I said that, ooh, one of the things that happens is that these sickle cells they love to upload things, right? So most people that have sickle cell disease over time, they're going to, or include their spleen, right? They're going to have spleenic infarction. In fact, by around age four, age five, most people that have sickle cell disease, their spleen's are gone. Their spleen's a literally what? God. Their spleen's a literally God. And what does, why is your spleen important? Well, let me explain. Your spleen helps you deal with encapsulated organisms. Many of you remember it with a mnemonic shin. Like strep pneumo, hemofluos influenza, and like sermeninjitis, right?

It protects your gains in encapsulated organisms. So, if your spleen is gone, you're going to have a lot of issues with encapsulated organisms. That's why people that have sickle cell disease, right? It's one of the reasons why we actually screen newborns, right? Because when you figure out, do you have sickle cell disease or not? When you figure it out as quickly as possible after you're born. Because if we figure out that as a newborn, you have sickle cell disease, want to put it on penicillin, want to put it on penicillin for at least five years, right? Although, you know, some people have penicillin allergies. So, instead of doing that, you know, put them on a marker instead, right? But basically, we want to put you on antibiotics for at least five years, right? So, I can reduce your risk of infection. We can reduce your risk of infection, especially normal, coco infection. So, if our friends at the NBA, they say, oh, by offering prophylactic antibiotics to this patient that is diagnosed with sickle cell disease. Again, what kind of prevention is that? What kind of prevention is that? That's an example of primary prevention, right? We know they have sickle cell disease, but what are you giving the prophylactic antibiotics for? You're giving those prophylactic antibiotics because you do not want them to develop sepsis from some bog, from some encapsulated organism. They don't have the encapsulated organism issue.

We're trying to prevent them from developing that encapsulated organism issue. That's going to be a primary prevention. Again, I don't know why I keep eating these preventive preventive preventive things. But just take it from me, that this is something that's high you to know for your exams. We're going to leave it at that, right? So, that's why they get those prophylactic antibiotics, right? And they can say, oh, the institution of prophylactic antibiotic therapy will most likely reduce the risk of sepsis from which of the following organisms. And the USM is in their great wisdom. They'll put strep pneumo as an answer. They'll put hemofluosam fluenza as an answer. They'll put an insurement in jadedness as an answer. They'll put a bunch of other organisms. Now, you'd be like, come on, define like, how do they expect me to answer this question correctly? Like, literally, they are giving me a bunch of encapsulated organisms. How do I know which one to pick? Well, let me tell you this. The one you pick is the one that is the most common, right? That's why, again, you see many podcasts. I mentioned, ooh, the most common cause of this. The most common cause of death. This, the most common cause of death, xyz, right? So, what is the most common cause of sepsis of nasty infection in people that have sickle-cell disease? It's going to strep pneumo. That's very, very high you to keep in mind, right? So, that's why we give them antibiotics, right?

We give them antibiotics, giving these prophylactic antibiotics for five years has been shown to reduce mortality and morbidity from the mucoccal infections, okay? It's been shown to reduce mortality and morbidity, right? So, if they ask you, they give you a question. I'm really going to try to be in questioning more today. If they give you a question about a person that has sickle-cell disease, and they ask you for interventions that improve survival in sickle-cell disease, one of the answers you want to pick is the institution of prophylactic antibiotic therapy, okay? The institution of prophylactic antibiotic therapy. That's pretty high you to keep in mind, for example. Now, another weird epidemiology like question you may get on your test. What if they give you a question about a person that has sickle-cell trait? And then they'll say, you know, compared to the general population, what is this person's risk of death? Or what is this person's life expectancy? Remember, people that have sickle-cell trait, believe it or not, they really have a normal life expectancy compared to the general population. The risk of death is not elevated compared to the general population. The USML is they have this weird habit, provocationally, picking and choosing certain diseases where they care to see. If you know if these people have a normal life expectancy, or if they have a reduced life expectancy compared to the general population, right?

So, clearly, people that have sickle-cell disease, they have a decreased life expectancy compared to the general population. But, we would have sickle-cell trait, they have a normal life expectancy compared to the general population. That's pretty high you to keep in mind for your exams, right? So, having sickle-cell traits does not increase your risk of death, or does not make you die earlier compared to the general population. Although, one thing that's actually pretty high you to keep in mind, is that people that have sickle-cell trait, even if they don't have sickle-cell disease, you want to try to advise them to not go too crazy on intense exercise, because think about it, if you go super crazy on intense exercise, that's going to cause a few problems, right? Because, remember we said that, man, many of the things that trigger cycling is having the oxygen-effect tissue, tissue that is hypoxic. Well, if you're exercising so hard, you're really, really crushing the oxygen levels of some of your tissues, right? That will promote some theoretical badness in people that have sickle-cell trait, right? So, it's just generally wise to when, when you put out sickle-cell trait, it may not be the smartest idea in the world for you to engage in super, super, super intense extreme exercise, right? Most exercise that I will say, like, maybe like 90% of the population does, is probably not a problem.

But, when you start going into extreme exercise, they can start having problems as a result of those things, right? And again, please, I'm going to throw the disclaimer, please. None of this podcast is for medical decision-making. This is entirely for educational purposes. So, please, if you ever want to make a decision, please send in your health consultor physician. Okay. Okay. I feel like I've hit this whole idea of anti-validic, it's pretty hard. So, I think I'm going to go ahead and continue, right? But, some other things, right? Again, I said that these sickle-cells, they can occlude blood vessels, right? When you occlude blood vessels, that's how you start having issues, right? You see all these kids with acute pain crises, a lot of chronic pain, right? All those things arise from those viso-clusive episodes, right? And the thing is, obviously, because these cells, hemolize pretty well, these people are going to have anemia, right? Most people that have sickle-cell disease, they're hemoglobin testores between seven and eight grams per desoliter, right? Again, don't say, wow, divine, if I see it over eight or under seven, it's not sickle-cell disease, no, right? I'm just giving you like some rough approximation. It's really going to be somewhere between seven and eight grams per desoliter, between seven and eight grams per desoliter, right? Your anemia is neuromacetic, neuromacromic. That's pretty important to keep in mind for your exams.

Sickle-cell disease is usually going to be a three-dollar neuromacetic, neuromacromic, anemia. So, in fact, what are some quick integrations they can make here? What if they give you a question about a person that has sickle-cell disease? And their hemoglobin is like three, something that is abnormally low. If you see that, that question is testing an A-plastic crisis from probably 19, because yes, don't get me wrong. When you have sickle-cell disease, your hemoglobin is low. But the hemoglobin is three or three is a little too low for sickle-cell disease. Think of an A-plastic crisis in those circumstances. Or what if they give you a question about a person that has sickle-cell disease? And they tell you that, hmm, this person has a, they're, they give you in the question, you'll have to give you, they tell you in the keystem that, wait, this person does have sickle-cell disease. But then you notice that their MCV is like under 80, so they have a micrositic anemia. And they will ask you, ooh, what should you, or let me ask you this, what should we be thinking about in that question? When you see something like that, you want to think about a person that is a compound hit or zygote, a compound hit or zygote. What in the world do I mean by that? I mean, a person that has sickle-cell disease and also has thalassemia of some sort. I'm going to say that again, you want to think about a person that has sickle-cell disease and thalassemia of some sort.

Because remember thalassemia, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, ten times, whoa, we will, we will, we will, we will this comfort. So, going to keep these things at the back of your mind. Now, let me ask you this. What would you expect to be through of the reticulocyte count in a person that has sickle-cell disease? What do you expect? Remember reticulocyte are immature blood cells. Well, guess what? The retic count is going to be high. This is going to have a high retic count. They're going to have a high retic count, a high retic count. Why do you think they'll have a high retic count? They'll have a high retic count because they humanize their cells. Their reticulocyte has been broken down all the time. So, the body is like, oh, man, I need to find a way to replenish these reticulocyte cells. Right? But it's almost like the bone marrow can not replenish the reticulocyte fast enough. So, it's going to put out immature blood cells. So, you're going to see a higher reticulocyte count.

The bone marrow is going to respond to that chronic ebolicis by pumping out these immature blood cells. So, let me ask you this. What if they give you a question about a person that has sickle-cell disease? And they tell you that, man, this person's retic count is decreased. Hmm. If you see that, what should you think about on your exams? Think of a parable being 19, what? A plastic crisis. You see, I've told you now about a parable being 19a plastic crisis from two dimensions for a sickle-cell question. They can give you a quite person that has sickle-cell disease and your hemoglobin is just too low for sickle-cell disease. You see a hemoglobin like, of three or four, of two. That's extremely low. That's not just sickle-cell disease that play. There is something else going on, right? The person has, right? A parable being 19a plastic crisis. I also just told you that, hmm, a person that has sickle-cell disease, they tend to have increased reticulocyte counts. You see a person that has sickle-cell disease and their retic count is low. Think of a parable being 19a plastic crisis. Why? Because parable being 19 has this nasty habit of torching your red blood cell precursors. It torches the red blood cell precursors. If you damage a person's red blood cell precursors, guess what? You're not going to be able to make red cells. So those reticulocytes, well, they don't drop from the sky. They come from somewhere.

So if you've damaged the red blood cell precursors, if you've inhibited them with this virus, this single-stranded DNA virus, and that's something that's higher to know for your exams, parable being 19 is a single-stranded DNA virus. That's pretty high to know, actually. These people do not even be able to make those in mature cells. So if you see a lower retic count on a present has sickle-cell disease, I want you to think of a parable being 19a plastic crisis. I want you to think of a parable being 19a plastic crisis. And then, what if they give you a question about a person that has sickle-cell disease? Because if you think about it, how do you generally diagnose sickle-cell disease? You generally diagnose sickle-cell disease with hemoglobin electrophoresis. You're going to diagnose sickle-cell disease with what? Hemoglobin electrophoresis. Typically, when a person has sickle-cell disease, what would you expect from hemoglobin electrophoresis? There's like one or two questions that I've come to mind, but let me give some background first. What would you expect? Well, if a present has sickle-cell disease, you should not see any hemoglobin A. Remember, hemoglobin A is normal adult hemoglobin. That's alpha 2 beta 2. You're not going to see that, right? What you're going to see is you're going to see hemoglobin S, and that's what you're going to see. Hemoglobin S is basically you have SS, right? You have SS, right?

Although one kind of hemoglobin you mention electrophoresis, and a present has sickle-cell disease, is hemoglobin F. You'll see hemoglobin F on hemoglobin electrophoresis. Hemoglobin F is alpha 2 gamma 2. So guess what? It does not, because remember the mutation in sickle-cell disease is in the beta-globin chain. It's in the beta-globin chain. It's in the beta-globin chain. So because the mutation is in the beta-globin chain, it's going to be pretty obvious that, okay, wait. If you have a hemoglobin that does not contain beta-globin, that's probably going to be increasing these people. So you're going to see an increase in hemoglobin F. You're going to see an increase in hemoglobin F. That's alpha 2 gamma 2. When we talk about pharmacotherapy for sickle-cell disease, you're going to see that hemoglobin F kind of coming to play, again, Now, let me tell you this. What if they give you a question about a patient? They tell you that this person has sickle-cell disease or this person is suspected to have sickle-cell disease. And they tell you that, you know, they perform hemoglobin electrophoresis and they find hemoglobin S, right? Hemoglobin SS, you know. But then they also tell you that they find abnormally increased amounts of hemoglobin A2. And abnormally increased amounts of what hemoglobin A2. If you see that, what should you be thinking about on your example? You want to think about a person that has sickle-cell disease and what? And beta thalacymia.

Sickle-cell disease and what? Beta thalacymia. So notice, I have hit you from two angles for this combination of sickle-cell disease and beta thalacymia. What other ways they can introduce this? Let me just summarize again. Number one, you'll see a person that has sickle-cell disease and you'll have a departure from the norm and have a micro-setic hyperchromic anemia. Most people that have sickle-cell disease have normal-setic, normal-chromic anemia. You see a person that has sickle-cell disease and they have micro-setic, hyperchromic anemia. That person has sickle-cell disease and they also have thalacymia. Okay, what's another clue? I just mentioned it. You see a person that has sickle-cell disease, they do hemoglobin electrophoresis. They don't just hemoglobin S. They see a lot of hemoglobin A2. Remember, hemoglobin A2 is alpha 2 delta 2. That person has sickle-cell disease and they have beta thalacymia. They have beta thalacymia. Again, these things I'm seeing me seem loyal to you, but I promise you these things are super, super, super high-youtu-no for your exams. Super, super, super high-youtu-no for your exams. But I guess maybe one thing that may be helpful to talk about here is what if a person has sickle-cell trait? What would you see on hemoglobin electrophoresis? You're going to see hemoglobin S because they're their heterosigals. They have one of the bad hemoglobin. You're going to see hemoglobin S. That's number one. What else are you going to see?

You're going to see hemoglobin F, believe it or not. You're going to see hemoglobin F, right? Alpha 2 gamma 2. But you're also going to see hemoglobin A, right? That's alpha 2 beta 2, right? Because those people are heterosigal. So they have one functional beta-globing gene, right? But remember, so how would you differentiate with hemoglobin electrophoresis between sickle-cell trait and sickle-cell disease? Sickle-cell disease, you will not find any hemoglobin A. Sickle-cell trait, you will find hemoglobin A on electrophoresis. Again, please make sure you understand this stuff. Many hemoglobin apathes are diagnosed with hemoglobin electrophoresis. All right. Now, what if they give you a question about a person that has sickle-cell disease? And they show you that this, they give you like a set of hematologic labs. And notice that the person's bleak-leck count is like 500,000 or 600,000. Right? And our friends at the Mbimis will ask you, what is the underlying mechanism? What is the underlying mechanism behind this hematologic lab finding or behind the thrombocytosis? Well, if you see this, I would really hope you are saying, or functional is plenty. Right? You will put an answer that relates to the spleen. Right? Remember, again, is plenty is why they get these infections, these encapsulated organism infections. But under thing with is plenty is also, they are going to get like a, almost like a functional thrombocytosis.

Because remember, your spleen holds about 30% of your, of your pleatlets. Right? So, if you see a person, if you see an elevated pleatlet count in a person's asi-cell disease, is because your spleen does not work. Right? The asi-cell disease is pretty much gone. Right? The spleen is pretty much gone. And also, remember, some white cells, many resources don't talk about this. But white cells also sequester it in your spleen. So, if a person has like your spleen gone, your white cell count will increase a smidge as a result of that. Right? We'll increase the smidge as a result of that. Again, kind of keep these things at the back of your mind as you, as you study. Okay. Now, how do we manage sycosell disease? How do we manage sycosell disease? Well, the first line to remember, sycosell disease is hydroxyurea. Hydroxyurea. Right? What exactly does hydroxyurea do? Hydroxyurea pretty much increases your levels of hemoglobin F. Right? And the thing is, when you have more hemoglobin F within your red blood cells, it makes it difficult for those hemoglobin SS to polymerize. Remember, I said that that was the critical thing that caused many of the issues in sycosell disease. Those hemoglobin SS, especially in hypoxia, they love to, they just love to bind each other. Right? But when they is hemoglobin F, they're eating habits that polymerization process. Hemoglobin F, that's why it critically, it specifically helps.

In people that have sycosell disease, hemoglobin F, it literally prevents, it literally prevents, literally prevents that binding, that polymerization of those hemoglobin SS. It prevents those stains from binding. Okay? It prevents those stains from binding. It prevents those stains from binding. That's why hydroxyurea is so helpful because if you jack up your hemoglobin F, you jack up that hemoglobin F, you prevent that polymerization of those hemoglobin SS. Right? And again, what are some ways our friends at the MBM Es contest this concept? And by the way, this is going to be a two-part podcast. There's just so many good ideas that can be brought with sycosell disease and lots of integration. So I'm not going to try to like loot everything into like a super, super, super long podcast. I'm going to put half here and then half in the next podcast. But what are some things they can do? So they can ask you a simple question and say, or how do you manage a sycosell disease, first line treatment, hydroxyurea, end of story. But unfortunately our friends at the MBM Es, they have a few other ideas. Right? They can literally ask the same question many different ways. Let me explain. They can say, which of the following interventions? So they will give you a sycosell disease, because you're like, oh yeah, totally get this. This is a sycosell disease. Right? And then you'll see which of the following interventions has been shown to reduce the incidence of acute painful crises.

And then you'll see one of the answers be hydroxyurea. Hydroxyurea will be the correct answer. Right? Again, it does reduce the risk of acute painful crises. Again, the USM Ds, these days, and I see this in many of my review courses. They don't come out and ask questions directly. They will ask like a peripheral question. A peripheral question. Right? Like instead of asking, how do you treat this disorder? They can ask, which of the following reduces the incidence of acute painful episodes? Right? Or you can say, which of the following interventions reduces the incidence of acute chest syndrome? Right? Or you'll see, which of the following interventions reduces the need for blood transfusion? Right? Or you can say which of the following interventions improves survival? Improves survival? Right? Hydroxyurea reduces, improves survival in people that have sycosell disease. Right? It literally improves mortality by about 40%. I give you not. Right? So notice we've talked about two interventions that improves survival in patients that have sycosell disease. Number one, taking microleads, I mean, taking penicillin, right? Microleads for people that have penicillin allergies for five years, right? After they are born, it reduces the risk of death, like mortality or morbidity, from normal coca-infections, incapacitated organism infections. But we also said that again, taking hydroxyurea does improve survival. And again, hydroxyurea, there are many ways they can test that concept.

We know it's the treatment for sycosell disease, I've explained how it works. But again, the other ways they can go after this is, they can say again, intervention that reduces the incidence of acute painful episodes, that's going to be hydroxyurea. Intervention that reduces the incidence of acute chest syndrome, that's going to be hydroxyurea. Intervention that reduces the need for blood transfusion, that's going to be hydroxyurea. Intervention that reduces mortality, that's going to be hydroxyurea. Remember the way that those antibiotics I talked about reduce mortality, is by reducing your risk of sepsis from encapsulated organisms, right? They don't necessarily reduce your risk of all these other issues. Although they, they, they, they, they indirectly because think about it, many times when people have acute chest syndrome, most times, most of the time, most of the time acute chest syndrome is from an infection. Or let me not say most of the time, but a lot of the time is from an infection, like from Michael Plasma or Chlamydia. That's actually a high olfactory to know for your exam. We'll probably talk about that in more detail in the next podcast. In fact, I think this is kind of going on for a little long.

So let me go ahead and pause here, because there are many other things with treatment, like exchange transfusions, how do you manage the acute chest syndrome, ACE inhibitors, believe it or not, they play a really sickle cell management, iron, chilellation therapy, pulmonary hypertension, and just many other things. So I think I'm going to go ahead and pause here. And then we'll pick up from here in episode 500 and eat. Now one thing I want to say here, I do offer review courses for the USMLE, so if you're interested, I have a 20-hour course for step two and step three. Many people have taken this courses and found it to be extremely helpful. If you're preparing for your comp exams, or if you even want like a good bread-over-view for a show of exams, the course is precisely what you need. And then I have a 25-hour step one class that's happening in, I have the 20-hour step two step three class happening in February, the 25-hour step one class, many people studying for step one or complex one, or people that are taking step two, step three or complex one, or people that are taking step two, step three or complex two or three, and have poor foundations, they also take that class as well, finally to be extremely helpful. And that's going to be taking place in the first week of March.

And then I have classes that are first step one or other with step three, I have a 20-hour, NV Me test taking strategies class, a four-hour biostatistics class, and a five-hour social sciences quality improvement on healthcare systems, ethics, communication professionalism class. Again, these classes are not lectures. If you expect to be a lecture, then these classes are not for you. They all over Zoom, but they are all pretty much based on clinical veneers. They all based on exam style questions, because it's much better to show you the classic presentations of things number one. And then two, show you how the test information three, show you how this information can be integrated with many disciplines, and then four, help you understand pathophysiology, and also help you just get better at critical thinking and reason. And that's those are features of many of these classes. If you like the way I teach, you will love these, you will absolutely love these classes. So if you're interested in any of them, shoot me an email through the website. And then also four, one or one, two, and for step one, step two, and step three, and also complex, level one to three. My tutor for personal and clinical med school exams, and third year show of exams, also help with applications like your applications, mock interviews, personal statements, rec letters, and things of that nature. We all do this pretty much in a one-on-one setting.

And then I have this podcast on Apple Google and Spotify, and I also have my You Tube channel, Divine Intervention, USMLE, podcasts, and videos. That's why I post the videos that I make. And then I actually have another website called Divine Intervention Lifelessens.com, Divine Intervention Lifelessens.com. Basically every week I post like two life lessons. I use the Bible, biblical perspective, two podcasts usually on Fridays and Sundays, I address a life lesson. We have almost 250 episodes on there. And there's actually an Apple podcast associated with that. Okay, so I'm gonna stop here for today. Thank you for listening to me. This podcast is gonna be a part two. I'm gonna stay tuned for that super, super high-yellow stuff in that one as well. And I think you're gonna be really, really blessed. And you're gonna be thankful on your exams for this podcast. So thank you, bye for now. Thank you.

Substitution of glutamic acid for valine in the beta-globin gene.

Hypoxia (low oxygen tension).

1) Slowed blood flow/stasis $\rightarrow$ risk of venous thromboembolism; 2) Vessel occlusion $\rightarrow$ ischemia/tissue death; 3) Hemolysis (premature destruction).

Streptococcus pneumoniae.

HbS, HbF, and normal adult Hemoglobin A.

It increases levels of fetal hemoglobin (HbF), which prevents the polymerization of HbS.

An aplastic crisis, most commonly due to Parvovirus B19 infection.

Glu $\rightarrow$ Val substitution in the beta-globin gene.

Functional asplenia leads to elevated platelets (thrombocytosis) and potentially increased white blood cells due to sequestration failure.

HbAS will show normal Hemoglobin A; HbSS will not show any Hemoglobin A.

To prevent sepsis from encapsulated organisms, especially S. pneumoniae, due to functional asplenia.

Hydroxyurea; it increases Hemoglobin F (HbF).

Compound heterozygosity for sickle cell disease and beta-thalassemia.

Glu $\rightarrow$ Val substitution in the beta-globin gene.

Functional asplenia leads to elevated platelets (thrombocytosis) and potentially increased white blood cells due to sequestration failure.

HbAS will show normal Hemoglobin A; HbSS will not show any Hemoglobin A.

To prevent sepsis from encapsulated organisms, especially S. pneumoniae, due to functional asplenia.

Hydroxyurea; it increases Hemoglobin F (HbF).

Compound heterozygosity for sickle cell disease and beta-thalassemia.