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YEAR 1 CSI - FRESHERS FLU & SICKLE CELL ANAEMIA - RECORDING

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Summary

This on-demand teaching session offers a deep dive into Clinical Science Instruction (CSI) exams. It's led by Kate Goldwater Bren, a seasoned medical professional with vast experience in this field. Explore tips and strategies to approach the exams, understand what content is usually examined, how the questions are laid out, and ways to pinpoint the most useful material to study. The session also offers detailed insight into how CSI manages to tie together diverse medical topics, such as virology and hematology. Attendees can find answers to their queries related to course content and are encouraged to actively participate in discussions. They are also reassured that the session will help them better prepare for the exams. Join to get a clearer understanding of what to expect from the CSI exams, the content to focus on, and methods to enhance your exam performance.

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Description

We hope you all enjoyed your first MedEd CSI Tutorials of the year, and found it useful!

Hope to see you all again for Cases 3 & 4.

Learning objectives

  1. Understand the structure and format of CSI exams: By the end of this teaching session, learners should understand how the CSI exams are formatted and understand the type of questions that are often asked.

  2. Learn effective study methods for CSI exams: Be able to identify and utilize effective study techniques to prepare for the CSI exams, such as using flashcards for short term retention and practicing graph interpretation.

  3. Understand how to interpret the content covered in the course: Be able to accurately interpret and understand the course content, identify key information and understand how it can be applied in the exam.

  4. Develop skills in answering different types of questions: Students will learn how to answer various types of questions, including graphs, list-based questions, and identifying incorrect sentences.

  5. Understand and prepare for the overlap between POM and CSI: Recognize the overlap between the material covered in the POM and CSI courses and become prepared for questions on this shared content in the CSI exams.

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Computer generated transcript

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The following transcript was generated automatically from the content and has not been checked or corrected manually.

So you can have any source as well, questions that we don't go through. Um Right now you'll have to practice with before your exam. So, who am I? My name is Kate Goldwater Bren. Um I use a them pronouns. I'm in year five, which basically means I'm very old. Um And essentially, I'm just here because I've done this before. I've done three years of CSI for my sins. Um I've had um distinction, stars and distinctions in my years at medical school. Um So like that isn't, you know, flex, that's kind of just like, that's why I'm here. That's why I have something to say that you might find useful because I've done well on these exams. Um and shout out to medics, drama and sex expression, which are both wonderful societies that you should get involved with and just say, you know, there is life outside of medicine and CSI. So essentially, you know, the point of this teaching session is not to just recover the content because you've covered the content and the content is, you know, not supremely difficult. What does CSI like? It likes its cell biology, poem stuff, it likes kind of list based things where you have to find the one sentence that is incorrect and it likes graphs. So, what I'm trying to do is give you a flavor of what the questions, what CSI is gonna do with all that content that they've given to you so that you're in the best position for the kind of funky questions that they like to ask because they, they aren't just going to ask you like what virus causes flu, they're going to frame it in some weird way. That's going to make you really confused. And I think that's why CSI is difficult because now the content is challenging, it's how they ask it. So what I've tried to do is get loads of questions on all of the teaching you've had that gives you the best idea of what CSI is actually like. Um And that means that what I really wanna know. So just to kind of skip ahead is we're gonna cover all this stuff, which hopefully is not surprising to you. Um But what I really want to know is what are you guys worried about? What do you really want to get out of this? What do you wanna know? And we'll make sure to go through that stuff and that can be both, you know, I wanna learn about androgenic shift in which case. Absolutely. Or I want to do the graph questions or how are you feeling? You know, how are you what do you want to know about year one? Cool. So, this is recorded. Yes, that's an easy one. I'm going to fail. Well, firstly, if you do it doesn't matter because there's loads of CSI. But the fact that you're here, the fact that you're interested, you know, um, that's probably means you're not gonna fail. Ok. I probably was confusing by saying pom. Um, I don't mean that there will, like there is overlap, like there is definitely overlap. You'll probably see that more in your sickle cell tutorial that you have at eight because you know, sickle cell is hematology, right? Like I'm in year five, I'm still learning about sickle cell. What I mean by that is that they want to test you on the palm stuff. I think someone with CSI, people think it's going to be very clinical, but they like to give you those questions on like the receptors. You could easily get a question on the names of the different virus receptors. And I think that's the point I was trying to make um where you can get the slides afterwards. Um That is Hannah's question in the chat. I'm sure you'll be made aware of that or I'll put my email at the end. You can always email me, you don't need to know anything that wasn't in the CSI. To be clear. CSI is very self contained, but often there is overlap. So they'll teach it to you once in POM once in CSI and you can kind of enjoy the overlap, the detail you need. Absolutely. So, the whole point of this is to give you an idea of what the content they can examine is and how they examine it and how you find that out is kind of something that you pick up over time, you pick up over your time at medical school during the exams. So, for now, you know it because I'm an old, I've been through it before and I can give you my synthesis and then over time you'll get better at knowing what they like to ask graphs. Definitely, we can go straight to the graphs how to prepare. I think we're gonna kind of talk about that throughout. But for me, I would really say try to do these questions, come to these lectures because that will give you the closest idea of what the questions are and like, I'll talk about it with the graph questions. But there are loads of like, I always get my graphs from the CDC website. They have so many complicated graphs. So you can get a friend, you can each pick a graph from the CDC website and write some questions on it. And that's a really great way to practice. Um How is C how does CSI work? Um So please take all of this with a pinch of salt just because I did CSI a while ago. I've obviously talked to the CSI lecture lead. You know, I don't think it's changed very much, but if you've heard different things, please listen to like your faculty, not me. Um But essentially you first set the IRA. So the IRA is 10 questions on each like CSI. So 10 questions on flu, 10 questions on sickle cell that'll be mixed together and then multiple choice. So your question might be like, it's literally like the questions in this. You know, what, what is the virus that causes flu COVID, flu Rhinovirus, tuberculosis? Right? And you answer that and you get a grade out of 20 and then you do it well, you don't get your grade but you will get a grade out of 20 then you do that again with your team. And what it means is you sit there and you go oh I put COVID and you, but everyone else put flu. So let's pick flu. Oh OK. Flu was right. And then you do a kind of team assessment thing that in my opinion is just designed to be painful. We can talk about the team assessment thing a bit if you want. Um But they're kind of a bit pointless. No one's ever failed CSI because of the team assessment. How question the question style for CSI in my experience is very specific and that's what I've tried to mimic here. Um They're often very, I don't wanna say pedantic, but for instance, they'll like giving you, you know, four sentences and one is right. And the rest have like very small reasons why they're wrong. So again, I think we'll go straight to the graph questions. That sounds like what people want to look at and I think that will give you a really good idea for how to do that. Um Yeah, and you don't need to usually be like, again, the level of detail unfortunately is everything they go for the tutorial because they like to be that specific. So I would say like, you know, the way I did it was, I would literally make an flash cards on like everything they said. And then for the three days before the exam do all those anti flash cards every day because it's quite short term retention. But because they like to be very specific, you can need to know things in quite specific detail. Um And yes, we will get to the questions. Um again, like P CSI is more just overlap in the content. But everything you learn in CSI is the only thing they can ask, they cannot ask you random stuff. They will ask you about the Zola healthcare and stuff. I have that in my um slides, we can totally talk about that. Um not focusing on the right content. I think the key thing to they will try and assess you on all of it. So usually like, you know how M CSR you go through and you have like your 10 tasks or whatever, you can usually kind of go, there's gonna be a question from each of the tasks and I think where people can go wrong sometimes is not learning like the Zola healthcare stuff because they go, oh, this is really silly. Then they will ask you about that and it's actually kind of easy marks in terms of the format. Um Again, when I did it, it was tens per lecture. And you'd usually have within that 2 to 4 graph questions and 2 to 4 kind of clinical e questions. So like Fred has, you know, a runny nose, does he have flu COVID or whatever? And the rest would be kind of more science based. No extra poem. I am sorry for confusing you with that. Um Access to me again, I think the med people can answer in the chat. I just lecture for them. They don't actually like pay me or give me any detailed information. Um It is virtually impossible to fail CSI. You are not going to fail CSI to be very clear. Um unless you have the worst team imaginable. So you're kind of having to do it all by yourself, you will not fail CSI. And if that happens, talk to the faculty because they can actually support you if like your team isn't showing up and stuff. Um So for Sa Qs, so I think this is more like your final exams based but again, you'll get the actual information from faculty for um SA Qs, you can kind of write as much as you want for VS AQ. It's normally limited to four words. But again, like check that and again, back in my day, I think the IRA was 60% the TA was 20 the TA was 20%. But they may have changed. That is one of the things they like to fiddle with. You are not assessed on it again. After the exam, you can forget about it. So in terms of prep, what I would usually do is just a very intense two or three days to be prepared for the exam, it is worth doing some prep because otherwise you just don't know stuff and some of the questions are factual recall. But as I say, what I would do is I'd go to the med lecture, I'd do my cards on everything that I then like delete after the summative CSI. And it's kind of quite an intense like little period. What is Zola healthcare? We can absolutely go through that. Thank you for the person who wants me to be paid. I appreciate that. Um And your, the CSI. Yes, I think it's on the Note Bank anyway. But um yeah, we can email me and I can sort that out. It sounds like maybe you do have short answer questions on CSI. Now. Um If so they will also ask the Helman Falk model. But yeah, if they're asking you for short answer questions, just do what they say basically and you'll get it wrong once and you'll never get it wrong again. There aren't really CSI question banks, but usually like, what I would find is that the med, the med ed lecture would have questions in that lecture. I just do them a couple of times and once you start to get familiar with it, you can first do like redo the graph questions from the previous CSI S and you can try with your friends. Like, what if we did a few questions ourselves? Ok. So it sounds like what people are kind of wanting to know about is the Zola healthcare model, the Hellman's folk model stuff and the graft stuff. What I'm gonna do is I'm gonna go all the way to the end with the graph. We'll then go back and do the um folk model stuff and then we'll see how much time we've got left and what you guys wanna cover. So hopefully, that sounds good. Um And you get your results premium. So for the T app, it takes a while but you get your results for the IRA and T wrap straight away and then you basically know that you passed, right? Like um and that's kind of the important one and yes, I'll put my email in the chat at the end just because I'm swapping between screens, but you'll definitely have that. Um And I personally use just let an do its magic. I put the cards in, it tells me when to do them. Um Yeah, and we can go over the cold and flu mechanisms as well. The other bit of the I wrap and T wrap, which I assume you still have is the TIA which is why you do like a little project as a team. OK. So if you have more, put them in the little question thing at the side, but let's talk about some graphs, just me clicking through it like the speed of light. Um Here we go. So I believe in learning by doing. So what we're gonna do is we're gonna do one graph question. You guys will all get a bit of time to give it a go and then we'll talk about it and then you'll get to do another one and hopefully you do better and there's some medical education research that shows it a really good way to learn. So here is the first graph question. You should be able to click on the photo on your phone to make it bigger. I can see, I can see some brave people have had a go. I think we'll let everybody have a go at, think about what their answer is. First, we had about 50 people before. So if we get up to 40 that will be good. Somebody's put in a question. You are not good because we're gonna talk about how to make this work. But yeah, these, these are kind of scary to look at, but I also want to say this is what CSI will do. They'll give you a graph with lots and lots of stuff. And it's about how do I pair down from all this stuff to actually be able to answer questions. So let's see what people were thinking. Ok. Nice. So you've got a pretty, pretty good split of responses and I can see some are still coming in, but I think it's maybe everybody. So let me go through before I tell you what the right or wrong answer is how I would approach this. So you see this graph, it is a scary graph and you think chat we are cooked. I do not know what to do off which is very valid. So what I would do is ignore the graph. No one cares about the graph. What matters is which statement can be correctly deduced from the graph, right? So do is I will read each statement and go back to the graph and be like, can I check this statement against the graph? And some sometimes it can be useful to just check the graph first. Do I know what this is? So I think like, you know, look at the axis positive test reported to the CDC. OK. 2018, 2019, positive tests by week. And like that's just a very basic initial thing, right? Am I confident that I know roughly what this is talking about? Yes. So II look at the statement so twice as many people had flu in the 10th week of 2019 compared to the last week of 2018. So I think this if we pull it, pull it up, so it's ok. So what is the 10th week of 2019? So I'm going straight to that, which is this kind of big bar here. And literally, if I was in the CSI exam, I might get a pencil out and light it against my ipad to make sure I've got the right line because it's a very complex graph. And then what's the last week of 2018 at this point? I might get another pencil. Literally, no shame. And it's kind of this sign, right? So, you know what you think is OK. Well, this does look broadly right in the last week of 2018, about 1700 ish people had flu. And in about the 10th week of 2019, about 1000 200 people had flu. That seems logical. But then what you have to think is, is that what the graph says? Does the graph say how many people have flu? It says that in the positive test reported to the CDC that might not correctly, tell me how many people have flu. There could be loads of people who have flu. But they don't have a positive test or they have, their test wasn't reported to the CDC. So I'm kind of thinking, well, the graph is right for that one, but the wording is a bit fuzzy maybe if the other three are definitely wrong but that not sure. This one. OK. Is this a different thing? So how do I look at the strain? So that's this extra bit of the graph that we haven't looked at till now. That's the colors h3n2 is this kind of lovely shade of purple and like you can barely see that on the graph. So this seems to not be true. So I'm happy to say it's not the most common influenza strain and hopefully I'm not going too fast. Like I can see there's been some questions and I'll come back to them. But um if you have any questions, please let me know. So. Ok, no more than 200 positive tests for influenza B were ever reported to the CDC in any week of the 2018, 29 flu season. Well, that's quite nice already in that. It's using the language of the graph. It's saying which thing that I know this graph shows is true then. OK. Influenza B, let's see for these nice kind of citrusy colors. And what I would do again, I'll get my pencil. I would like it just below the middle of this box. Does it look like anything is crossing the pencil? No. So that, that would be my kind of, it doesn't look like turn positive test and this is using the correct language. It's not saying cases of influenza B which we don't, it's saying off show. So that I would be like, I think that's right. And then I think this final one, if I wanted to go back and check everything, I bet that seems to have the same problem as this first one. Like according to the graph, like, yes, there were never more than 3500 positive tests for flu. But that's not, you know what, like this statement is saying it's whoever had influenza. And if you just think about like in the US, there's 3 300 million people like it seems very unrealistic that there was never that many people who had flu. So I would say that. Yeah, this one is the right one and hopefully you can see how, what I've done is quick. Look at the graph, go to the statements, go back to the graph and this really crucial thing of what does the graph actually say? Not what feels like it's correct. Like if you need a five second wise graph questions, which of the question stems uses the same language as either the title or the X or Y axis. That is a pretty good, will we write 80% of the time test? OK. Um OK, fine. Uh Tell me how long you have for the individual Ira um off the top of my head. I want to say something like half an hour. But please check that. That is definitely information that's been shared with you with the CSI team. Cool. So if you've all had a look at the graph, you've all heard me talk through what I think is a really solid approach to the graph questions. So hopefully for this next one, everybody's gonna get it right. Love to see because it means that the education is working. And again, if you have questions, please do put them in the comments. Um also by P and II just read pneumonia and influenza. Um just co mental has a limit on how much you can write question. Uh Why is there no key? Um There, there is a key. Um They've got the arrows rather than a color code, but the arrows are a form of key. Yes. OK. That will talk about um used in graph labels. Um But yeah, I think for now just pretend this says weak. Um So I got up to about 100 last time. So I'll maybe aim for 75. Um OK. So just to address the issue. So with the legend, I think again, she about they'll try and throw weird graphs at you. So I agree that this like little arrow thing pointing to different lines is like not really it in terms of graph design, but they might give you a graph that looks like this just because it forces you to kind of think about it with the axis. Um in your CSR, you could complain about this. This means weak. This is because I've screened a graft from the CDC and I haven't like. So ideally like all the words would be spelled out and you wouldn't get this like weird acronym that is defined elsewhere on the CDC webpage. So like, don't worry about that. That won't happen. Ok. So let's see. Ok, so unfortunately, I have, I have failed as a teacher. Um Well, let's see. Got, got lost. Ok. I'm, I'm neck and neck as a teacher. Um So I think most of you are kind of split between these answers and I think, you know, if we look at, if we just look at these two, so you've got the pneumonia and flu epidemics in 2015 and 2018 were the most of it. So my, my question to you guys, that is what does severe mean and I think this is something that CSI will do all the time. They will try and trick you because if you look at this graph, it's easy to go. Oh, there's a lot of deaths in 2015, there's a lot of deaths in 2018. That's bad. But the graph doesn't tell you that it doesn't have any criteria for severity. It just gives you percentages and the threshold for an epidemic, right? So, that feels like it's right. But you can't deduce it from the graph because this word severe is so like fuzzy. Like it doesn't, the CSI team are hoping that you'll kind of get tricked and imbue it with your meaning. But actually, there always has to feel it very concrete anchored in the graph and I can, I can see the question answers ticking over as I'm speaking. Um So hopefully you get the idea that what I'm trying to say is that this is the right answer because it's both true and it's what the graph says. Like it doesn't require you to bring any value judgment you might say for this to be absolutely correct. It should be in between um you know, 2020 15 and 2019 and you know what I would take that and if you made that challenge to the C sri think they would probably take that. But I think um still compared to this, I would say this is the best answer because it doesn't require you to like interpret the idea of severity. It's just what the graph says. Um Similarly, this one, the green one is just wrong. You can see the percentage gets up to about over 10%. Um And then for this one, they've kind of tricked you because this is a percentage, not a raw number. And again, they'll often try and trick you with the units. So it's worth like looking at those units. Reco that's a percentage and not a number. Yeah, because they have quite a lot of questions. Is it reasonable to say more deaths means higher severity? The problem is that it's still an assumption like we have no definition of the word severity. Like it would definitely be reasonable if I wrote a paper and said I'm defining the, the severity of an epidemic of most deaths. I go, this is the most severe, but that hasn't happened in that graph. So you can't deduce it from the graph. It requires you to bring in a step where you kind of assume this and why it's a reasonable assumption in assumption. I think hopefully, that makes sense. It's where is December 2017? No. So if you look at the um graph, it's kind of like it starts to drift up at kind of the 50 mark. So I was two weeks of December, but then it is primarily over the first sort of 10 to 15 weeks of 2018, which again, you could say like fine, that's not spring. That is a reasonable critique that I think the um again, you could make off the CSI team and I can definitely rewrite this to say like January 2018 rather than spring, which would make it a better question. Um Yeah, fine. I am being called out on the spring. Um I think that's definitely a valid critique and you could make that in the C of the CSI team because you have ability to challenge the questions. I'd still say that this is a more correct answer because you're not having this like fuzzy concept around severity that you're having to bring in. Um But yeah, like, absolutely, I should change it. So it doesn't read brain. You are all very correct. OK. So hopefully you're all, if not happy, you feel you have a systematic approach, you can bring to the graph questions and that you have an understanding of the key places where the CSI team will try and trick you up. If you're thinking, I do not have those things. Please ask a question because that's what I want you to take away a systematic approach to the graphs and an understanding of common areas where you can trip up king assumptions using the wrong units. Um All that kind of thing. Yeah. Oh You are. Yes, you are and do ask a pen and paper if they don't give it to you, that's fine. OK. So a lot of you asked about the, some of the Helman's for model and Zola. So this hopefully will make you feel that you are not cooked for CSI because this is like essentially what they can ask you about these things and they are very easy. So feel free to have a go at this question and have a look at your comments. In the meantime, roughly how many graph questions are there in the whole CSI usually between two and four. So it's worth cos I remember like, for me with CSI, I would go through it and I would always lose two marks on the graph questions. So I was like, actually, if I get the graph questions, right? That's like one of the best things to improve my mark personally because like the factual questions, you can kind of like, you know, crack out the and you'll remember like, the fact about how flu viruses work is Jamal. Gay Jamal is, in fact bisexual. It's, but yeah, I tried to write these questions inclusively because God knows the faculty doesn't. Um OK, so you've got about 72 people. Let's have a look at what everybody thought. Yes. So I think this is a really good example of how this stuff. Like if you put this on a flashcard, it will just, you'll remember it. And then like, because these are all very easy things, they've just got silly names. And I think that's why some people have gotten like in between sanctioning and interference with personal relationships because you're like, oh, I don't quite remember what these are, but his personal relationship is involved. So maybe it's this. Um But if we look at Zola's model, so he based, yeah, like there's a slide from the internet that I quite like, but it's actually all these things that can be like defined. So this interference with personal relations is usually that like stops you doing something. So it would be like the tingling in his finger is like stopping him going bowling, his husband, which is his favorite thing. Um Like it's interfering with that relationship or it might be like a more risk example is like my drinking, my, my partner has said if I don't stop drinking, they're gonna leave me. And that's my like criteria to seek help for, for alcohol, substance abuse. Sanctioning is being sanctioned by another person. So that would be like, you're like, oh, I don't know if this is bad enough to go to the GP. And your partner says, yeah, it is, you should go to the GP, which is what has happened here sanctioning. He's decided to go because his husband has said you should go interpersonal crisis is like you're having a big life crisis. Um Essentially that I think is relatively self explanatory. So I'm just trying to sit back. So that would be like, again, you know, my wife broke up with me because of the drinking. So I will now seek help. Um And temporalizing is usually like a deadline. So that would be if it's not better by Friday, I will go to the doctor and I think these are all kind of things that like make sense. I can relate them to when I seek help from the GP, for example, but if you just put this on a flashcard, so you know, the specific words that they're gonna ask the mark is so easy, right? So I think that's where it's kind of like these are really nice questions, but they will ask you about it. If you think about it, they can only really ask you what are each of the Zola's triggers. So as long as you take the time to like make sure you're aware of them, it's quite easy. Um Yeah, Zola is just a guy called Zola. Um We can, we can Google who he is later. It's, but it's, it's literally just his surname. Um He was a medical psychologist. Um And OK, difference between interpersonal crisis and interference. That's, it's a good point. So interference is it stops you doing something in your social life. So that would be like I really like playing football and my knee pain is stopping me playing football. There's not been any crisis like nothing bad has happened, you know? No, but it's stopping you doing a fun social thing, whereas a crisis would be reaching like something really bad happening in your life. So the example Zola gives a divorce and death. So that might be um I know and I've seen this like this is a real patient that I saw literally today. It would be my dad died of prostate cancer. Can I have a PSA test? You know, it's like this crisis has made me think, do I have a health problem? Should I get checked? Out. Um Yeah, and yes, the answer to the question was sanctioning. No, what happened there? I'll just go back and take that for you guys. Cool. And then the next thing is basically exactly the same with Hellman's folk. And again, just hopefully everybody gets the idea for this, but we can go over the folk model. Yeah. OK. A good number of responses. Hopefully after the graph questions, it feels pretty, you know, relieving. Cool. Let's have a look. OK. I think most of you have got, got the idea. So and you know, that is the right one. So just for context. So literally, these questions are what has happened, why, why to me specifically, why now and again, you can probably recognize that like these are all questions that, you know, you want to know when you go to the GP, right? Um The slight again, this isn't a lot of information. The reason I would say it's not what has happened is if you just think about it, it does like say he wants to know like what the illness is. So I can't really like explain it better than that. I think you've got the why now that moment, which is just kind of to avoid saying now and really tipping you off. And then he kind of emphasized why me rather than what has happened, you would get a bit more information than this in the CSI. But I think hopefully, like it really is just that simple. And again, hopefully you can kind of proceed by elimination a little bit. Um Yeah, so in terms of the other information, so kind of the rest of it is a lot of the virus biology and I think one person did ask to go through that. So I'm gonna go through some of that. Now again, we have kind of, I think about um, 15 minutes, so he might not get through all of it. But I'm gonna kind of go through the, you know, essentially about how viruses work and the other stuff that we're kind of skipping over again, you'll get the slides, you can look at all of it is a kind of, um, what are the difference between flu colds and COVID, which is, is a kind of learning exercise, but there's some questions there to test your knowledge. Um And how they really like this thing about the fact that like, you know, exercising too much makes you more likely to get colds. Like they'll give you a question. It's like Bob is training for an ultra marathon and the answer is like, Bob is actually more likely to get a cold than like the person who does yoga. Um Oh, explaining why the other answers were wrong for the Hellman's Folk model. Um Yeah, we can go back to that quickly cause it looks like there's still some questions. Yeah. What might be something quicker? So essentially why me. So why me is correct. So why he himself has become ill? What has happened? There's just nothing really here about like what, like when you get this one state and it doesn't include the word what? And I think that's kind of why the why has this happened is is wrong. Like if there's a question that was this one versus why me and why has this, why now and why has this happened? It would be really tricky. Um But because this includes the what answer that kind of makes it wrong. So it's more, this is the best answer. And I think it's worth bearing in mind that that's often the case with CSI. Some of the questions are factual and there is a correct answer. But especially for this kind of question about like the folk model, it's always, it's a bit of a fuzzy concept. Anyway, it's a way of understanding how people present to the GP. So there is like a little bit of fuzziness where it's more the, the what has happened is definitely wrong. So you can exclude those options. Hopefully, that makes sense. I know there's a couple of other questions. Yeah. It's more that it's paired with the like what has happened to make those answers wrong rather than like that in itself is wrong. And it's worth bearing in mind that CSI likes to do that quite a lot. Like they'll give you things and it's like three of the four clauses in a sentence are right, but one is wrong. So you have to go through quite forensically, you can't just go on like vibes. You have to really be quite clear and you usually do have the time to do that as well. Ok. Back to the fun virus biology for the last kind of 10 minutes. So we'll just get as far as we can if you have any questions, ask them now as well. And otherwise you've got the slides, I'll put my email. So you can always like reach out before the exam. So key concept to get into your cells, viruses have to bind to something on the cell membrane. Like if you remember one thing about virus biology for your CSI, they have to bind to a membrane protein and then that makes all the rest of it kind of make sense. Like why do I have to learn these membrane proteins? Well, because it's how the virus gets into the cells. So it's important. So similar painful CSI question, which of these correctly pairs the virus and the protein it interacts with on the cell membrane and this is just a fast one. So if you, if you're not sure you haven't revised, just give it a guess. Got a question about cortisol levels and exercise. Um I imagine that they do because it's stre like it's stressing your body, but it might depend on the kind of exercise like if you're doing very intense yoga and you're like relaxed. Um, I would honestly say that I would give that a Google and have a look at some papers because it's probably quite a nuanced concept and a lot of the CSI stuff is very much like it down to the level you need to know. And obviously the reality is way more complicated. Ok. Cool. So, just in the interest of time, let's have a look. So yeah, most of you have done your studying that is exactly bang on. Um So essentially it's something you need to memorize Coronavirus interacts with Ace two. Again, you know, what is this? What does this mean? These are all questions for like smarter people or for doing your immunology BSC for now, you know, the virus sticks to this thing to get into the cell COVID to ACE two flu tosic acid and rhinoviruses to I am one just got to memorize it, which it seems like most of you kind of have. And hopefully the COVID ACE two thing is, is pretty familiar from living through the COVID pandemic. Yay. Um So, and just to kind of, again, this isn't from your CSI that I think this is beyond what you cover in CSI. So just to give you an idea of what that means, like what viruses do because I think it's cool. Um And essentially it's gonna get into the cell so it can get the cell to make loads of copies of it and get the coffee spit out. And the reason I put this in is not like to be, oh my God, there's all this extra stuff you need to learn. But sometimes it's easier when you have just a bit of that overview of like what's actually happening. Like why does a virus want to get into a cell? But on a very simple level because it can't reproduce by itself. So it needs to get into the cell to use all your cellular machinery to make more viruses. And that can just help like contextualize everything that's going on. Um um Yeah, so I believe it's probably a glycoprotein because most so cells don't really tend to just sit like long chains of sugar, but I don't really want to on that because I'm sure someone does. Um but often they're glycoproteins in low molecules. So that's a protein with a sugar kind of attached. But again, like I'm teaching you the simplified CSI version. If somebody Googles that and you tell me it's actually something else that would be great to expand my own learning. Um uh Appointment was that was both COVID-19. Um OK. That is definitely different to how I was taught it, which is quite like simplified between each virus causing. Oh OK. So the point is Coronavirus is like a family of viruses. So there isn't like one Coronavirus. So this Coronavirus essentially or like Coronavirus in the sense of that causes COVID is SARS CO 19. I hope I got that right. But then there is a whole family of Coronaviruses and lots of Coronaviruses cause colds. And that is often because of where they bind like in the respiratory tract. So in general, like the reason flu causes a worse or worse quote unquote, like a more severe infection is because it combined deeper down in the lungs where there are different um proteins expressed by your cells. Again, please don't at me on like the names. Um And often like if you think about it, let's say a virus is essentially stickier. It can bind better to those cellular glycoproteins and it will get in more compared to another virus that binds to the same glycoprotein, but is less like sticky. So it might bounce around a bit before it can get into the cell. That might not be the most kind of helpful. But hopefully, it gives you an idea. There's a family of Coronaviruses. They have different proteins on the outside of different molecules in the respiratory tract and therefore they can cause different like levels of disease. Yeah. So he's mentioned like what's in the Yeah, exactly. Um So if your immune system can't recognize something, so it could kind of depend like some diseases with reinfection, it's worse like dengue, dengue is very cool. Um But in general, like if your immune system can't recognize, you might get a worse initial reaction to go through all those phases of the immune response and stuff. Um, I think somebody put in something about folic acid being a glycoprotein, which is nice. Yes, it's nice to be. Right. It's a kind of glycoprotein signaling molecules are usually glycoproteins. Um, I don't believe for the CSI, you very much need to know about the R angiotensin system. You will need to know about it for BRS later in the year. But unless they've very much changed the content, which I don't believe they have, you don't really need to know about it. They don't cover it. Yeah, some, some people have put some things in for this already, which is great. Um I think just in the interest of time just because this is a really important thing to get through flu is kind of special cos it has these multiple proteins that can interact with salic acid. The two you need to know about a hemagglutinin H A and neuraminidase N A matrix two just like kind of is there and does its thing. Um They don't really teach well in detail, but they do teach that it exists and it's actually the big difference is that hemo glue glutenin get, it is kind of the glue to get the virus into the cell. It's the sticky bit that sticks to that outer sialic acid glycoprotein. Um But then if you think about it, if the virus sticks to the cell, when it's trying to get out of the cell, it's gonna stick to the cell too. So, neuraminidase is like scissors that comes along and releases the virus from the cell. Um And this should just be a nice kind of graphic illustration of that to ignore this. It also just because it's all way more complicated than CSI will teach you. But actually, hemagglutinin will bind to the salic acid and then the virion will try and come out. So V is the word for like baby virus, it will get stuck. A near many days will come along and like unstick it. And again, something they could definitely do on CSI is give you an image like this and tell it's an influenza virus binding and say what is the red crescent or what is the blue line or what is the green stick or whatever? And the idea is that you should know, well, it gets into cell by binding sic acid. So this bit on the cell must be sic acid or this must be hemagglutinin. And that's like a way they can kind of essentially test factual knowledge but kind of add in of like making you reason back from the diagram. Uh And somebody asked a question but it's gone missing. Um Yeah. So I know some people have said like I haven't. So vision, is it too late to do? Well? Absolutely not. So, as I understand that your exam is on Wednesday, this would usually be kind of the point where I would start studying like maybe the weekend before. It's definitely not too late to just try and cram all the facts using flashcards and to be honest, like there's not too, too much that is like you really need to understand in depth. Like hopefully you understand the virus biology because people weren't worried about that. You now have a good understanding of how they're gonna ask you about these kind of fuzzier things like the folk model. And you have a good understanding of how to approach the graph questions. So you should be really well equipped for your CSI and I know we've got to eight o'clock. So I need to hand over to AFA. Um But just to quickly go through. So red thing is makes two like the other molecule on flu. Um The yellow part is some other cellular molecules that you don't need to worry about. Wouldn't Yida also? Yeah, this is a very lovely question. Um The answer is that this is probably a great question. There are probably some very, very interesting papers about it. I don't know the answer off the top of my head. But virus biology is fascinating. That is a, it's really great that you're asking these questions. I can't give you the answer, but hopefully it's as good as to go. That is a really excellent thought process. Google it. I'm sure some very intelligent person has spent a lot of their life thinking about that. Um Because virus biology is just so cool, like the way they work is just so cool and they're very well adapted to what they do. Um Yeah, the the question is asking you what the receptors were rather than just telling you for a learning process. Cool. Um So, oh yeah, the red crescent is sialic acid. The red little line on the virus is probably matrix two. But yeah, no, thank you guys so much. We'll get a feedback form at the end. So I would really, really appreciate it. Um If you could fill that in because it's really, really useful for me. Um I will put my email in the chat now, so please do get in touch and I'm sorry, I couldn't have my camera on as well. Um because that usually makes it a bit nicer, but hopefully it was still useful and I'm sorry, I can see people putting in the middle chat, but I couldn't see that. So I'll have a look now while Aoife is getting started just in case there's anything I can help with as well. But yeah, thank you guys all so much and absolutely best of luck. You're all gonna smash it. The fact you've taken a whole hour out of your day on a Monday to come to CSI. I think you, you are all gonna be fine and really best of luck. So yeah, I'll hand over to Aoife now. Hello, everyone. I don't know if you can hear me. Um, bear with me. I'm just gonna set up my slides. Give me one second. Um I know you guys haven't had a break. So if you want like a two-minute break before we get going now is the time to take it. OK. Can everybody hear and see those slides? Hopefully you can. Um So I'm doing this presentation as an actual uh powerpoint. So I might not be able to share the mental with you going through, but just to give you guys a bit of information about me. So my name is Aoife. I'm in my final year at Imperial, which is very sad. Um Also means that I'm very close to graduating. Um And I'll be doing your tutorial on sickle cell anemia. So this is actually the fifth time I've given this presentation, I'll keep an eye on the chat. So if you guys do have any questions or if I'm going too fast or too slow or anything needs clarifying, just let me know. Um OK, so let's get going. Hopefully I won't make this too long. So I know you guys have already had another lecture. Um But just an overview of what we're gonna go through. So we're gonna look at the structure of adult cell hemoglobin. We're gonna look at the structure of sickle cell hemoglobin, um electrophoresis of sickle cell anemia, which some people find a little bit tricky. So hopefully will simplify everything and just make it very easy to understand um blood film analysis, which again, people do find a bit tricky, but we'll break that fully, fully down. Um the symptoms and signs and symptoms that you get with sickle cell anemia. Uh how you diagnose sickle cell anemia, how you manage sickle cell and your assessment of the patient. So of Mowa A Bebe. Um and this patient hasn't changed since I was in first year. So hopefully the content hasn't changed too much. But if there's anything that needs clarifying again, just let me know in the chat. Um and we will also go over a little bit of ta guidance. This is a bit that I'm not 100% sure whether or not it will have changed. So base it off of your um I think you have your freshest flu CSI first and then your sickle cell one. So kind of base it off of that, but hopefully, um it won't change too much. Ok. So we're gonna start with a ment. So I've got the code at the top of the slide. It's 48796012. And I just wanna know what you guys know about hemoglobin. It can be absolutely nothing. It can be very, very basic. Um Let me know if her is open. Hopefully it is and I'll give you guys a couple of minutes to just write down what you understand. Ok, good. I don't know how many of you there are. Let me just have a look. Ok? No, just a couple more. Ok, good. Um I'm not gonna share the mental with you guys because I don't want to uh get off the screen and not be able to get back. Um but some really, really good answers. Let me just have a look. Someone said literally nothing that is completely fine. That's why you came to the lecture. Um We got a couple of reads. Yep. Yeah, good. OK. So range of answers. Very good. OK. Next, I wanna know, what do you guys know about anemia? And it doesn't have to be perfect. Definition can be very, very basic, can be nothing completely fine. I'll give you guys a few more minutes. OK. Again, some really good answers. Um We've got lots of people saying reduced hemoglobin, which is really good. Um Someone said anemia is bad. Yeah, anemia is pretty bad. We've got some people talking specifically about the red blood cells and how that might affect their morphology, so their shape. Uh and some people touching on the different types of anemia, which is great. I don't know if you guys have had your heme lectures yet, but you don't need to know too much about the specific types of anemia for this CSI. You only really need to know about sickle cell anemia and have a broad understanding of what anemia itself is. Which hopefully will do by the end of this lecture. So let's start by going through the structure of adult hemoglobin. So as many of you said, really, well, it is a quaternary protein. So it's got two alpha chains, 100 and 41 amino acids each. You do not need to know how long the alpha chains are. That's just a bonus bit of information. Um and two beta chains, 100 and 46 amino acids each. So the beta chains are a little bit longer. But this is the important thing that you guys need to know. Two alpha chains, two beta chains and normal hemoglobin, which we call adult hemoglobin. Um and four he molecules bind to oxygen. So the main thing to take from that is that hemoglobin binds to oxygen. That's how our red blood cells carry oxygen around the body. So we find hemoglobin in erythrocytes, which is just a fancy word for the red blood cells transport oxygen from the lungs to the peripheral tissues. So, the tissues all the way at the ends of your bodies, the edges of your fingers and your toes and it transports carbon dioxide from peripheral tissues to the lungs. Hopefully, this is all very like GCS E kind of knowledge. Um but this might be a little bit different. So properties of adult hemoglobin, which we shorthand as H BA um the chains are arranged tetrahedrally. So some of you said it's a quaternary protein, it's the same thing. It just means that there's four of them. So two other chains, two beats chains. Um and it's an allosteric protein. So what that means is it changes shape when it binds to the oxygen. So if you guys remember from a level, your oxygen dissociation curves, the hemoglobin slightly changes shape depending on the number of oxygen molecules that are bound to it. And that allows for a cooperative binding effect. So it allows the hemoglobin to bind oxygen in the most efficient way as they about the structure of hemoglobin. But the main thing is two alpha chains, 22 beats chains. The difference comes when we're talking about sickle cell hemoglobin. So we're gonna look at why is sickle cell hemoglobin bad? And how is it different from adult hemoglobin? So, sickle cell is autosomal recessive, which means you need two of the genes to develop the trait. So you need two genes that are mutated to develop sickle cell anemia. And the mutation is in the beta globin gene. So when you have one mutated beta globin gene and one normal uh hemoglobin gene, you get sickle cell trait. When you have two mutated, you get sickle cell disease. So, autosomal recessive, um it's also quite useful to just be aware that the beta globin gene is shorthanded to H BB. Whereas the alpha globin gene is H BA, the HB is just the hemoglobin and the B just tells you that it's b uh so normal hemoglobin forms this nice tetrahedral structure. It doesn't really bind to each other and it doesn't really stick together. However, sickle cell hemoglobin tends to clump together inside the red blood cell. And if you guys can see this kind of banana sickle shape, when the hemoglobin clumps together, it creates the sickle shape and that's why we call it sickle cell anemia. So, in terms of what the mutation actually looks like. It's a non conservative missense mutation, which is a lot of words, that just means the sixth amino acid on the beta globin chain, which is glutamate gets swapped with vine. So we've got our glutamate at position number six swaps to, to vine. And just to explain a bit more about why this leads to the sickling. If we go back, we can see glutamate is quite hydrophilic. And what that means is it responds very well to a water based environment. So that means that the red blood cells don't tend to really stick to each other and they don't tend to really stick to the blood vessel walls because they kind of thrive in a water environment. They sort of slip over each other when we swap that to valine, which is a bit more hydrophobic. It means that they don't respond as well in that water environment. So they kind of precipitate out a bit more. And that means that they're much more likely to clump together and stick to each other. So that's why you end up with that clumped hemoglobin, which gives you the sickle cell shape. Hopefully, that makes a bit of sense. Um Unfortunately, for the CSI, you do need to know specifically that it's at the sixth amino acid and we swap from glutamate to valine. So just kind of be aware of that. Uh ok, so we're moving on to the next mentee. We've got some true or false questions. So first true or false question is sickle cell disease is caused by one mutated H BB and one normal. Well, let me just hide these answers. OK. I'll give you guys a few more seconds to respond to this. Oh OK. OK. Nice. So we've got the vast majority of people say that it is false. Um Very, very good for those of you that said it's true. Remember, sickle cell disease is an autosomal recessive condition. So when something is recessive, it means you need two copies of the mutated gene to actually show the trait. So for sickle cell, you need two mutated HB genes to actually develop sickle cell anemia. If you have one mutated and one normal, you develop sickle cell trait and we will talk a little bit more about the differences between sickle cell anemia and sickle cell trait at another point in the lecture. Um But hopefully that makes sense. Majority of people got it right, which is great. So, next question, um adult hemoglobin is composed of two alpha and two beta chains. OK. Let's have a look. Yeah, great. Everybody, everybody getting it right. Perfect. OK. So a mutation for H BS is a deletion mutation. So H BS just means sickle cell anemia. True or false. OK. Yeah. Well done guys. So most people saying false. A couple of people saying true. So remember the mutation for sickle cell anemia is a non conservative missense mutation. So at the amino acid position, number six, we're swapping glutamate for valine and valine is the one that's a bit more hydrophobic and that's why we're gonna get the sickling of hemoglobin inside our red blood cells. And what what I mean by sickling is we're just gonna get all those hemoglobins clumping together but majority getting that right. So in, in H PS in sickle cell, valine is swapped for glutamate at the seventh position on the alpha globin chains. Yeah, great. So, pretty much everybody getting that. This is false. It's kind of a mean question um because it's wrong in a couple of ways, but I can understand why you might say true. Um So it's not that valine is swapped for glutamate. The first point, it's glutamate is swapped for valine and it's not at the seventh position. It is at the sixth position. Um But hopefully that's fairly self explanatory. OK. One more um in sickle cell hemoglobin, uh it is more negative than adult hemoglobin because valine is negatively charged and glutamate is neutral. OK? A bit more of a split on this one, give you guys a few more seconds to respond. OK? So most people saying false, which is absolutely right. For those of you who said true, it's not that um valine is negatively charged and glutamate is neutral. The valine remember is hydrophobic. So that's the kind of important point rather than being more negative, it's more hydrophobic. So you end up with that hemoglobin, not liking the water based environment of the red blood cell and they end up clumping together to form that banana shape. So it's not so much about the negative charge. Uh OK, so that is it for our true or false questions. So we're gonna talk a bit more detail about the actual structure of sickle hemoglobin. So why is this harmful? Why do we really care if it's all sickling together? So sickle cell hemoglobin when it's bound to oxygen is actually fine. It kind of keeps the same shape as a normal adult cell hemoglobin. So it's actually OK, the issues come when the oxygen leaves the hemoglobin. So when it's carrying oxygen, it kind of functions like normal hemoglobin when the oxygen is released or it's deoxygenated, the beta globin change change shape. So this is supposed to represent a sickle cell hemoglobin. So we've got the little like red lightning shapes for the blob chains er when they are deoxygenated, they become this kind of um different shape that predisposes them to clumping together. And because of the hydrophobic valine, they're more predisposed to doing that. So they clump together in this kind of sickle shape. And that ends up changing the shape of the red blood cell rather than being a spherical shape. It becomes a sickle. And what does it mean clinically? So, clinically just means what does that mean for the person in real life? It means um well, we'll talk a bit more about that when we come on to the symptoms, but it means that those red blood cells are not as flexible, they're not as kind of plastic. And so they can navigate the blood vessels a lot less well compared to the uh spherical shaped red blood cells. So we're gonna look at some factors that affect um the sickling so that increase the shape of these red blood cells when we sickle shape. And when we're thinking about the factors, all we need to think about basically is what is gonna cause those red blood cells to release their oxygen. So if we start with acidosis, acidosis means that the ph of your blood goes down. So it becomes more acidic. When things are acidic, it tends to be due to an increase in carbon dioxide. So, carbon dioxide is acidic. When we have more carbon dioxide, it decreases the ph of our blood and the way that we get rid of that acidosis and combat the carbon dioxide is by increasing oxygen to those tissues. You guys think of like lactic acid in anaerobic respiration. The cure or like what helps that is increasing the oxygen supply to those tissues. So, acidosis is gonna cause our red blood cells to deposit more oxygen in the tissues that are acidic. And so they're gonna release more oxygen. And so without oxygen, they're gonna form this sickle shape, a low oxygen concentration is the same because if our red blood cells, if there's a low oxygen concentration in our blood, there's a low oxygen concentration in our tissues. And uh it's more important for us to have oxygen to our peripheral tissues than it is to just kind of carry it in the blood. So low oxygen concentration is gonna make your red blood cells take up as much oxygen as possible from the lungs and deposit it in the tissues, which again is gonna change the shape of our hemoglobin and form this red blood cell, sickle cell shape. The other thing that affects um sickle cell anemia, sickling is a small idius of the blood vessels. So that means that the circle part of the blood vessels, if you take a cross section is very, very small, that kind of does two things. The first one we'll touch on a bit more later, it increases the risk that these sickled red blood cells will get stuck. Because like I said before, they're not as flexible as the original uh spherical shaped red blood cells. So, if you've got a really, really small blood vessel that they're trying to squeeze through, it's gonna increase the risk that they're gonna get stuck. The second thing it does is if your blood vessels are very vasoconstricted, so the radius is much smaller, you're getting less blood supply to the tissues. So again, you're decreasing the amount of oxygen that you're delivering to the tissues. So when the red blood cells get there, they're gonna want to offload all of their oxygen to those tissues that are hypoxic. Hypoxic just means low oxygen. So the key point of this is remembering that the hemoglobin in sickle cell only comes together when it's released its oxygen. Ok. Why is this dangerous? So, I was talking about the blood vessels a little bit and them not being uh the red blood cells that are sickled, not being very flexible. If you have sickled red blood cells, there's an increased chance that they get stuck in your blood vessel and create a blockage. And when there's a blockage in your blood vessel, you're not gonna get any blood flow past that blockage and that's gonna decrease oxygen to your tissues and cause issues like ischemia, which means low oxygen um and necrosis, which is tissue death because there's no oxygen. So this can be very, very dangerous. Um We'll touch a bit more about the actual symptoms of sickle cell further on in this lecture. But this is the main principle to take away. And yeah, as I was saying, this is an area of ischemia um and infarction, necrosis. So, ischemia is low oxygen infarction is no oxygen and necrosis is just a type of tissue death. So this is an area of the brain where we've interrupted our blood supply. So we've blocked up the blood vessels with those sickled cells and we've ended up with necrosis in the brain. I'm just gonna have a very quick look at the chart. Um So uh what do you mean by the mutation being non conservative? So non conservative basically means um it's not producing the same thing. So in a conservative mutation, if you swapped one base for another base, you'd end up with a different triplet, a different codon, but you'd end up producing the same amino acid because if you guys remember from a level, there's multiple codons that will code for the same amino acid. So non conservative just means it's not gonna code for the same amino acid. So the protein you produce. In this case, the beta globin chains is going to be different. So that's why in sickle cell you see a clinically different picture than you do with somebody without sickle cell. I hope that that makes sense. Um That has been answered and that's been answered. OK, great. Thank you very much, Hannah. Uh OK. So we've got an exam style question kind of using the principles that we've talked through earlier. But if it doesn't make sense, don't worry, because I'll go through all of the answers. So, we have got Riva is a 45 year old woman and she is a sickle cell anemia patient. She ran a marathon and then she did an ab workout. So she did a lot of aerobic exercise and she is admitted to hospital with left arm numbness and chest pain. Do you think that she has collapsed? She's got a collapsed lung because she did so much exercise? Do you think that the build up of lactic acid increased cell sickling leading to an occlusion of her coronary arteries and a myocardial infarction. So, a myocardial infarction is just a blockage in one of the arteries supplying the heart muscle, meaning that the heart muscle has no oxygen. It's what, what lay people call a heart attack. Uh Do you think she's gone into exercise induced bronchospasm or do you think that the build up of lactic acid increased cell sickling which has blocked the brachial artery in her left arm? So that should be open. I'm just gonna have a quick look at the charts. Uh ok. So in terms of why cramping only happens when the hemoglobin is deoxygenated is because when oxygen is bound to the hemoglobin in sickle cell anemia, it kind of keeps its shape. So it stays that nice like uh ball kind of shape. Whereas when oxygen is released, um it changes its shape. Cos remember, hemoglobin is an allosteric protein. So it will change shape depending on whether it's bound to oxygen or not bound to oxygen. Um in a normal person, when it's not bound to oxygen, that change of shape is completely fine and it doesn't affect the binding of the hemoglobin to other hemoglobin inside the red blood cell. In sickle cell anemia that change of shape when you release oxygen combined with the fact that we've got a hydrophobic valine causes the hemoglobin to become more sticky and because the hemoglobin is more sticky, it will stick to all of the other hemoglobin subunits inside the red blood cell forming that sickle cell shape. I hope that that makes sense. But please let me know if it doesn't. Um Do you need to know about the hydrophobic pocket and how valine interacts with this? Thank you in AA I don't know what that is. So I'm gonna guess. No. Um And in terms of the lecture is recorded, I think the lecture is recorded. Um OK, so we've got a couple. OK. So we've got a real split between number two and number four. OK. Let's go through um I think there was someone in the chats thinking induced bronchospasm. So we'll, we'll talk through all of them. So nobody thought that she's got a collapsed lung because she did so much exercise. Um which is really good that you guys didn't think that it's not an unreasonable answer because she has got some chest pain. If you have a collapsed lung, your chest is gonna be quite painful. But with a collapsed lung, you tend to get very breathless as well because one of your lungs is not functioning, collapsed lung also doesn't have a lot to do with sickle cell anemia. So we can kind of rule that one out. Um, in terms of number three, which not a lot of people put exercise induced bronchial spasm. What that means is that the bronchi, so the airways delivering oxygen to your lungs are spasming like that. So that again would kind of present with breathlessness because you're not really getting enough oxygen to your lungs. She's got left arm numbness and chest pain, which doesn't really fit with that clinical picture. So in terms of the difference between two and four, the correct answer actually is number two and II agree. I think she would be very, very unlucky if this happened, but let's talk about why it's not number four. So you guys are absolutely right. She's used up a lot of her oxygen because she's done a lot of aerobic exercise. So that's gonna go to anaerobic respiration and she's gonna be producing lactic acid because she's done so much exercise. We know that acidosis is one of the factors we talked about that increases cell sickling because you're getting rid of all the oxygen from your red blood cells to try and fight that lactic acid in terms of blocking the brachial artery to her left arm. That would be a very good answer if she didn't also have chest pain. So when you're looking at clinical questions about people's symptoms, it's really important not to ignore specific symptoms and chest pain is a really big one. So any time someone has chest pain, it's kind of a bit of a red flag. So, numbness in her left arm, yes, blocking an artery would explain that, but it doesn't explain the chest pain. So the only one that fits with the picture of symptoms that we've got is that it's blocked one of her coronary arteries and she's had a myocardial infarction. When you have a myocardial infarction, you can get um left arm numbness as well. And that's because your heart is not pumping properly. Um The feedback because the heart muscle has become damaged, the feedback of blood from your left arm goes into the superior vena cava. And if your heart is not pumping properly and it's not releasing blood from the left side to the rest of your body, it's not going to be able to take blood back from the uh sorry to the, from the left side of the heart, it's not going to be able to take blood back specifically from the left side of the body. Uh Hopefully, that makes sense. Um So in terms of Ben's question? Ok. So is the acidosis due to lactic acid or increased carbon dioxide or both causing the sickling? It's probably more likely due to the lactic acid. When you exercise, you tend, you do get an increase in carbon dioxide in your blood, but your lungs are working really, really hard. So you tend to blow off quite a lot of that carbon dioxide. The issue is you're not exchanging gas at a rate that can keep up with the respiration of your muscles. So the main thing is you're gonna produce lots of lactic acid. That's gonna be the main thing that drives the acidosis. But carbon dioxide will definitely play a part as well. It's quite multifactorial. Um And then Ben says, if there's an occlusion in the brachial artery can arm muscle cells die. Yeah, absolutely. So, any tissues in your body that don't get a good enough oxygen supply can lose what we call their osmotic function. So they end up taking on too much solutes, too much water, the protein pumps in their membranes don't function properly because remember those need energy, they need ATP so those cells can absolutely end up dying. Um But the important takeaway from this is that uh acidosis increases your sickling and because those cells are not very flexible, they can't easily get through blood vessels, it can cause a blockage. So that's the main thing to take away from this. Ok. So we're gonna talk a little bit about uh electrophoresis. So what actually is electrophoresis? So it's a technique which is used to separate molecules based on two things. So the charge of the molecules and the mass of the molecules. So how heavy it is? So glutamate is negative, which is what we have in adult hemoglobin, valine is neutral. So valine doesn't have a charge. So adult hemoglobin is gonna be more negative than sickle cell hemoglobin. So sickle cell less negative than adult hemoglobin, whichever way you say it in terms of the mass, sickle cell hemoglobin and adult hemoglobin are kind of roughly the same masks, cos they both have two beta chains, they both have two alpha chains. So we don't really care about the mass too much. The main thing we care about is the charge and the important thing to remember is that sickle hemoglobin is less negative than adult hemoglobin. So with our actual electrophoresis slide, we can see that adult hemoglobin moves furthest towards the positive because opposite tract and adult hemoglobin is more negative than sickle cell hemoglobin. So it's gonna be really attracted to that positive end and it's gonna move the first towards sickle cell hemoglobin is the most negative. So it's gonna move the least far towards the positive. It's gonna be quite uh repelled by that positive charge. But two bands will appear for the sickle cell trait mutation because it's autosomal recessive. So remember with sickle cell trait, you've got one normal gene, one mutated gene. That means that you'll have some hemoglobins inside the red blood cells that are carrying that mutation. Some won't have that mutation. So that's why you get two bands because some of the hemoglobin has characteristics of the sickle cell and is more positive. Some is more negative because it's the adult cell hemoglobin. I'm just gonna have a look at the chart because this can be a little bit more complicated. OK. No, nothing on the chat good. So main thing to take away from this sickle hemoglobin less negative than hemoglobin. So it's more positive. So it won't move towards um the positive end because like charges repel adult hemoglobin moves furthest towards positive and we get two bands for sickle cell trait. OK. Moving on to blood film analysis. Also guys, please let me know if I'm going too fast or too slow or if you have any questions, I am keeping an eye on the chat and I know some of this stuff can be a bit complicated. Uh OK. So we're gonna start off with the most common things that you see with sickle cell. The first one being reticulocytes. So, reticulocytes are new blood cells. So when the bone marrow produces red blood cells, reticulocytes are kind of like the first form of red blood cells that will be produced. So they're baby red blood cells and they kind of look a bit bigger than normal red blood cells and they have a bluey purplish kind of tinge. We also get our target cells. So these are the cells that they look like a dart board target. They've got a central area that's very dark and a peripheral area that's very dark. And what the darkness means is that the hemoglobin is concentrating right in the middle of the cell and right at the edge of the cell, the paler area is an area of the cell where we don't have a lot of hemoglobin. Um And the reason that that happens is it's because the hemoglobin is starting to deoxygenate. So it's starting to release its oxygen and they're all starting to sickle together, but it's not formed the sickle cell yet. So that's why we get those target cells. Uh and they look like that or like this, you can also see target cells more often than not. You'll see target cells that look like this. And I think if they give you a blood film, they'll make it quite obvious, but just be aware um that sorry, normal red blood cells have an area of central pallor. So all of the hemoglobin is concentrated around the edge. Ok. Next one is regular red blood cells. Um And then finally, and probably the most obvious one is the sickle cells. So these are the ones that have a sickle shape, kind of like a banana type shape. So we're gonna talk about a bit more about the reticulocytes. So, remember I said those are baby red blood cells. Um They are the new red blood cells that our body produces. So why do you guys think sickle cell patients have a higher than normal reticulocyte count? I'm not gonna pick on anyone but just think it through in your head a little bit. Um OK. So are defective sickle cells, the ones that have had oxygen and then released the oxygen and now the cell is permanently in this sickle shape. They can't carry oxygen very well. Um And that's because all of the hemoglobin is kind of bound to each other and they've also reduced their surface area. So I remember surface area is very important for regular red blood cells to be able to load on loads of oxygen. They as a result, our body says we can't carry oxygen very well. And so we need to produce more red blood cells to be able to transport more oxygen to our tissues. And reticulocytes remember are the baby red blood cells. So they're the cells that are gonna be produced when the bone marrow is churning out more red blood cells to try and increase our ability to carry oxygen to tissues and they can carry oxygen. The difficulty becomes when those reticulocytes have had oxygen and then they release the oxygen, they're gonna form the sickle cells. So it's kind of like a temporary fix for a more permanent issue. Yeah, but they also don't have the flexibility of mature red blood cells. So, when reticulocytes are produced, they mature in the blood vessels and then they become mature erythrocytes. When they're the baby erythrocytes, the baby red blood cells, they're quite hard. So in the same way that sickle cells can get stuck. If you have too many reticulocytes, they can also get stuck in blood vessels and cause a blockage. The only reason that I am including this other slide is because I had somebody email me asking specifically last year. So I thought I'd put it in. Um But these little blue spotss that you can see in red blood cells are called Howell Jolly bodies. They might ask you about this. They might not, it's just kind of worth being aware of. Um So essentially what these are is they're fragments of nuclear DNA inside the red blood cell that would get filtered out by the spleen and we'll talk a bit more about what the spleen does, but there are bits of DNA that hasn't been filtered out. And this basically tells you that the spleen is not functioning properly, but to be able to recognize them all you need to know is that you'll see a red blood cell with like a blue dot inside it and it tells you the spleen is not working very well. Uh Yeah. OK. Some quick fire mentor questions. I know that we're running a bit over. Uh So why will two bands appear on the electrophoresis slide for sickle cell trait. I'm just gonna have a quick look in the chart. Uh OK. So, OK, so in terms of we've had two people asking what target cells are. So I'll just quickly go back to the picture while you guys go through the. So the target cells are these cells and it's important to distinguish how they're different from normal red blood cells. So target cells will have this area of darkness in the middle of the cell. Whereas the normal red blood cell has an area of pallor. So an area that's a bit more pale. The reason that target cells have, this is the darkness shows you where in the cell, the hemoglobin is very concentrated. So in a normal cell, you want the hemoglobin to be around the edge of the cell. But in a target cell, it is on the edge, but it's also concentrated in the middle. And that's because in patients, you can get target cells in lots and lots of different conditions. But specifically for sickle cell anemia, it's because the hemoglobin has kind of started to cramp together and it's all cramping in the middle of the cell. That's where you get this area of darkness in the middle of the cell. I hope that that makes a bit more sense. Let me know if you want a bit more explanation on that. Uh can a sickle cell become normal again if they can become oxygenated. So, de polymerizes. Unfortunately, they do not depolymerize, they are just permanently sickle and not really functioning properly. Um Then we have why do boat cells sometimes form in sickle cell patients? So both cells are very, very similar to sickle cells. The only difference between them is that the edges of the cell is a bit more blunted. So in a sickle cell, it's quite sharp. Uh I'll try and see if I can find one. So like this, this kind of, oh I don't know if you guys can see my mouse. Um but basically they're red blood cells that look like a sickle, but they don't have the sharp pointy edges at the end, they're a bit more blunt and they form in exactly the same way that sickle cells form. Um It's just a slightly different shape and the difference is literally just that the edges are a bit more blunted, but the formation is exactly the same way. So it comes from the hemoglobin all sticking together and forming that kind of banana shake. Um OK, so I'll have a look at everybody's ounces. Uh Yeah, really, really good. So most people saying because you've got um sickle cell hemoglobin and adult cell hemoglobin, autosomal recessive. Perfect. Um Just be aware that the amino A or the amino acid in adult hemoglobin, the beta globin chains is glutamate, not glycine. So just be aware of that. Uh OK. On to the next many questions. Which four types of cell would you expect to see on a sickle cell anemia, blood film? And I know we have actually talked about five, but I'm happy if you guys name whichever ones you can. Uh OK, so Ben says, I think I remember one of the lectures saying they can redissolve because oxyhemoglobin tends to not polymerize like the oxy because of the structure. Yeah. So this, this is what I was saying when the hemoglobin is oxygenated, it's oxyhemoglobin. So the hemoglobin is carrying oxygen. Um and it doesn't polymerize, but deoxy does depolymerize in terms of it may be possible that when the sickle cells are oxygenated, some of the polymer separates into the monomers of hemoglobin. But in terms of the sickle cells actually reversing their shape. It doesn't happen on a level that makes it clinically reversible if that makes sense. So it, it may be that it's possible for some of the uh for some of the hemoglobin to depolymerize, but it wouldn't be to an extent that it reverses the shape of the sickle cells and it wouldn't be on a level that it's not clinically um indicated for treatment. I hope that makes sense then, sorry if I've confused you more. Um I'm confused. Are we talking about normal red blood cells that aren't sickled that become sickled when deoxygenated sick cell anemia? Yeah. So what we're talking about is that in sickle cell anemia, the red blood cells or any red blood cell produced will have the defective hemoglobin chains. So they'll have chains that have the sickle cell mutation. When the, when the hemoglobin is carrying oxygen or when the red blood cell is brand new and it hasn't carried any oxygen yet, it will be kind of like a normal shape. Um But when it carries oxygen and then releases that oxygen, that's when the hemoglobin will start to polymerize and form that sickle shape. So basically in sickle cell, when you produce new red blood cells, they don't straight away form a sickle shape. They can, they look like normal red blood cells. It's only when they release their oxygen and become deoxygenated that they form the sickle shape. I hope that makes sense. Amani please let me know if it doesn't. Um If someone had sickle cell disease, not sickle cell trait trait, would they just show H BS on electrophoresis? Yes, because all of their red cells are affected by the defective hein chains. OK. Let's move on. Yeah. Very good. Everyone. Uh OK, let's move on to. OK. Is the end of the quick fire questions. So, very mini summary of what we've covered because I think we are kind of running a little bit over. So we've been through the structure of adult cell hemoglobin, the structure of sickle cell hemoglobin, the electrophoresis of sickle cell anemia. And what how the different manifestations of that show up for adult hemoglobin sickle cell hemoglobin and sickle cell traits. Um And we've looked at a blood film analysis. So what we're going to move on to in the next part is the symptoms, signs and symptoms, how we diagnose that and how we manage that and going back to the patient and a little bit of tap guidance, but we may not have time to talk about that too much. So this is our patient, this is Mowa. So in terms of the main signs and symptoms of sickle cell, we're gonna talk about how it can lead to vision loss, how it can lead to strokes, how it can lead to bone crises and what that actually is how it can lead to splenomegaly and how it can lead to jaundice. I didn't use to talk about splenomegaly and jaundice, but I had a lot of questions about it last year. So I've added it in. But the important thing to remember is that the principle for all of these signs and symptoms is exactly the same. It's that the sickle cells are not flexible, so they lead to blockage of the blood vessel. So for vision loss, this is a picture of the eye. Um and what I wanna draw to your attention to in this is that the blood vessels are very, very, very tiny, so they're very, very small lumens. So what happens in sickle cell is we get all of these abnormally shaped, sickle cells accumulating in the microvasculature. Micro just means very small and vasculature is your blood vessels of the retina and that causes a blockage. What that does is because there's a blockage here and there's no blood getting through, it increases the amount of pressure uh upstream of that blockage. So on the other end of the blockage, blood is gonna keep flowing in that causes the blood vessels to become damaged because when there's lots of pressure, the blood vessels can't really withstand it and they can burst, we get something called ischemia. So as I've mentioned, ischemia is when there's very, very low oxygen and when there's ischemia, your body wants to respond and it releases things called chemokines which are just chemical receptors to try and get other parts of the body to do something. When chemokines are released, it causes the blood vessels to produce new, very temporary, very delicate blood vessels called collaterals. And the point of these is to try and get around the blockage to deliver oxygen to the area. That's not getting any oxygen. The issue with collaterals is that because they're so delicate and they're so easily damaged, they can number one burst if the BP in them is too high and they can also grow across areas of vision. So two things that can cause vision. Three things actually that can cause vision loss is the ischemia. So if tissue dies because it's not getting enough oxygen, it's the collaterals growing over the areas of vision. So it's just blocked by all those blood vessels or it's the collaterals bursting because they're very, very delicate and the BP gets so high because it's downstream of this blockage. Let me check the chart. Um So Jake, you're actually getting ahead of yourself. We are gonna talk all about the spleen and how that is related to sickle cell anemia. Don't you worry, principle for all of these things is that it's a problem with the sickle cells not being flexible enough to get through the blood vessels. So that's the main principle for you guys to keep in mind moving on to your strokes. So two types of strokes, one is ischemic where we get a blockage in the blood vessel and we don't get enough oxygen to areas of the brain and that causes tissue death. One is hemorrhagic and that's where the blood vessels burst and we get loads and loads of blood in that tissue which stops oxygenated blood getting to it. So both of these things are an issue um because of the lack of oxygen to tissues of the brain. And that's what causes the damage in an ischemic stroke. And how sickle cell can cause that the same thing with vision loss, it's that the sickle cells block the blood vessels. So we get a lack of blood supply to tissues of the brain, which leads to ischemia, which is low oxygen and eventually infarction, which is no oxygen. Um So that's how sickle cell can cause an ischemic stroke and silent strokes. Uh You don't actually need to hear too much about that, but it's just strokes that don't have any symptoms. So we don't actually know that there's been a stroke in terms of hemorrhagic strokes. It's exactly the same thing as when we were looking at vision loss with the collateral formation. So we get angiogenesis, angio is blood vessel genesis is to make it. So we get collaterals forming. Um and those collaterals are very, very weak, so they're very easily broken and that can cause a hemorrhage and that causes blood to leak out into the tissues. And that's why we get hemorrhagic stroke. So that's how sickle cell can cause strokes, same principles as the vision loss. That's the same principles for all of these symptoms. In terms of bone crisis, you really don't need to know a lot about this, but it's the exact same principle. You get reduced blood flow to the bone marrow due to micro, meaning small vascular, meaning blood vessel occlusion, meaning blockage. So we're blocking the blood vessels that supply our bones with oxygen. And that prolonged ischemia, lack of oxygen leads to infarction, which is no oxygen. And the ischemia. Remember because ischemia is low oxygen, which will make our red blood cells want to offload more oxygen exacerbates the sickling. So it's kind of a negative er positive feedback loop. So this is just an X ray of healthy bones. This is an X ray of the sickle cell crisis. So you can see all of these areas of bone which look a little bit less dense, a little bit um more black that indicates tissue death. So that's how bone crisis forms. I'm very aware uh that we are running over time but is collaterals a type of blood vessel? Yeah. So basically the collaterals are are very weak, very quickly formed blood vessels that the body makes when there's not enough oxygen getting to the tissues. So because uh because they are so quickly made, they're quite weak. So hopefully that answers you guys question of what are collaterals? They're basically new blood vessels to try and get around the blockage to try and deliver oxygen to the tissues in a different way. So we're gonna talk about splenomegaly and this was Jake's question. Um What the spleen generally does is gets rid of nasty bacteria. You do not need to know the bacteria that I've put on here. It removes damaged or old red blood cells and it produces white blood cells. So that's what the spleen does in a healthy person. In particularly looking at sickle cell. When we have sickle cell, we have a lot of abnormal or kind of damaged blood cells. Those are our sickle cells. Now, the spleen has a lot of very, very small blood vessels in it. They have a very, very small uh radius and there's loads of them. So when a patient has sickle cell anemia, you're gonna get more blood flow to the spleen because the body wants to get rid of all those damaged blood cells. What that means? Unfortunately is we're gonna get loads of sickle cells in our spleen and in the same way as in all of the other symptoms we talked about because the blood vessels in the spleen are so small, that's going to lead to a blockage. So this is a blockage of our sickle cells that blockage um blocks blood flowing in or it can block blood flowing out. And when blood is not able to flow out of the spleen, you get loads and loads of blood filling up the spleen and that causes the spleen to enlarge. So you get like a massive, massive spleen if somebody's got uh sickle cell anemia, and there's a blockage and that's called splenomegaly. So the splen spleen megaly is just very big in terms of the other functions. If the spleen is so filled with blood, because there's blockage because of the sickled cells, it's not able to function as well as it normally is. So people with sickle cell anemia who have splenomegaly or a worse functioning spleen, they're less able to get rid of bacteria, which is one of the functions of the spleen and they're less effective at producing white blood cells. So both of those things together mean that people with sickle cell who have a big spleen are less able to fight infections. So, if you have splenomegaly, you're more likely to get sick. Basically, I'm just gonna have a very quick look at the chart. Uh, would most strokes not be both ischemic and hemorrhagic at the same time, I'm not too sure of the difference. So you don't need to know too much about strokes for the CSI. But basically, the hemorrhagic stroke is not necessarily due to a always due to a blockage. So in a healthy person, it can be because your blood vessels are a bit weak. If you've got something called an aneurysm, which is like a weak point in the blood vessel that can just burst and that can cause a hemorrhage. Um in terms of ischemic strokes causing a hemorrhage. Most of the time the damage will occur more quickly from a lack of oxygen quicker than it will be to break open the blood vessel because of the increased back pressure. So most of the time you'll see the symptoms of an ischemic stroke before it's got to the point where the blood vessel that's blocked has burst open. Hopefully, that makes sense. Ok, we are very quickly gonna talk about jaundice. So all you need to know about how you get jaundice and sickle cell is that these sickle cells are not healthy cells. And so they're more likely to burst open than normal red blood cells when they burst open, you do not need to know this whole process. They release something called bilirubin. And bilirubin is normally filtered by the liver and kind of removed in that way when there's so much bilirubin produced. So there's so many of your cells that are bursting as happens in sickle cell anemia. You and so yeah, bilirubin is removed in your feces through your kidneys in your urine and some of it gets reabsorbed back into your blood. But when there's so much being released by so many red blood cells bursting, your liver can't function and the bilirubin builds up in your skin. So that makes your eyes and your skin look a bit more yellow. It kind of deposits yellow bilirubin in the eyes in the skin and that's why you might look a bit more jaundiced if you have sickle cell anemia and that is all of the signs and symptoms. I know that was a lot of information. So if you have any questions, please feel free to ask, but we're gonna move on to our penultimate mental question. So, Sinead has sickle cell anemia while on a family skiing holiday, she suddenly experiences extreme joint pain in her left knee. How would you manage her? Would you give her an injection of morphine in her left knee? Would you advise her to stop skiing momentarily and take a water break? Would you advise her to stop skiing? Return to her hotel and apply a heat patch to her knee or would you advise her to call a counselor for cognitive behavioral therapy? And this is a bit cheeky because we haven't actually talked about the management. But using the principles we've talked about to see if you guys can work it out. Ok, so we actually have a bit of a split between all four answers, which is great. We'll go through them one by one. So giving her an injection of morphine in the left knee, that would definitely help with her pain, but it's not actually addressing what's causing her pain. So, not a not a terrible idea as a first resort, but you're not actually addressing the cause of the pain. Um The other least popular one was number four. It's always great to be thinking holistically um and thinking about mental health, but it's unlikely that cognitive behavioral therapy, which is a mental health therapy would really help her with her knee pain in that situation. So not the best answer. Um We had a bit of a split between two and three. So the correct answer is number three for number two, it's not a bad idea. If she stops skiing, she'll stop doing that. Um anaerobic respiration and hopefully increase uh the oxygen to fight off her lactic acid. Um and taking a water break will increase her BP. So that might reduce the risk of those red blood cells getting blocked, but it's not the best answer. Um The best answer is we're gonna want her to stop skiing. Go back to the hotel and apply a heat patch. And what the heat patch is gonna do is vasodilate all those blood vessels. So increase the radius. So increase the amount of space that the blood cells have to move through. So decrease the risk of the blockage. Ok. We're gonna go through this very quickly. I'm very, very sorry that we're running over. Um Oh, sorry. Can you repeat why? It's not number one? So for number one, yes, morphine will help her with her pain, but it doesn't actually address the cause of her pain. So the cause of her pain will be because her sickle cells are blocking some of the arteries supplying her knee. So she's having something called a sickle cell crisis and that's causing her some pain. If we open up those arteries and increase the amount of space that we have for the red blood cells to move through. Hopefully, that will kind of move all the blood cells that might be blocked uh down the blood vessels. So it'll resolve the blockage. The morphine will just get rid of the pain. So it's not the best answer. Um The heat patch is good. Yeah. So the heat patch is good. Uh The heat patch is good because it vasodilates all the arteries. So it increases the amount of space that the blood vessels have to move, the blood cells have to move through the blood vessels. Um, if hemoglobin clumping in deoxyhemoglobin is irreversible. How do sickle cell patients ever feel better after intense exercise? Yeah, it's a good question. Um, I think is what you're asking when they do exercise. How, how do they feel better when they've used up that much oxygen? So, a couple of things, number one, your red blood, your bone marrows will produce more reticulocytes. So it will churn out lots and lots of new red blood cells. Um and that will help patients feel better. And number two, the issues with doing um intense exercise is that the uh sickle cells get stuck. And so if the sickle cells get stuck, that's when you start getting pain because you're not getting oxygen to your tissues. So doing things like a heat patch or um uh allowing the physiological state of vasodilation that happens during exercise to take its course, can kind of make things feel a bit better and help oxygen get back to your muscles. Um But like someone was saying, um it may be possible that there is some reversibility that the hemoglobin does kind of declamp. It wouldn't be to an extent that it reverses the sickling shape of enough of your cells that it decreases the symptoms. I hope that that makes sense. Uh OK. So diagnosis, we've got electrophoresis, which we've talked about we've got screening so sickle cell anemia. Remember is a genetic condition. It's possible to screen people at birth to see whether they've inherited both of the mutations. So we can screen pregnant women. Um And there's also genetic counseling. So what that means is if you and your partner both carry the trait or one of you, one of you is affected, you have counseling as to what your chances are of having a child who's affected with the condition. Um And then the last thing is the sickle solubility test. So what this is is it's when we take a sample of blood from a patient, we think has sickle cell anemia. We add something called sodium dithionite as a reducing agent. You don't really need to know the specific name of that. Um And that basically causes hemoglobin to be released from the red blood cells. H BA will dissolve very easily in blood plasma, but the H BS is less soluble. So the solution will become turbid and it will become very, very cloudy. So that's how we can tell this patient will be a sickle cell patient. This patient will be uh not affected by sickle cell anemia. For the sake of time, I'm gonna move on, but I promise we're very, very close to the end. Um We're just gonna talk about management. So for this, think about the issues that sickle cell anemia causes and think about the different ways in which we can address those issues. So the first one is blood transfusions. And what that means is that you literally give the sickle cell patient somebody else's blood and you remove some of the blood that's affected by sickle cell anemia from that patient. So you're taking away some of the patient's blood and you're giving them somebody else's blood. And the point of that is to supply functioning red blood cells. It's kind of important to be aware that our body doesn't really have a way of secreting iron. So our body doesn't really have a way of getting rid of iron. And so they might need something called iron chelation therapy, which is where we use medications to get rid of the excess iron to prevent them from getting something called hemosiderosis, which is just when we get too much iron building up in our tissues. Second way is managing crises. So this is like managing the bad symptoms. You can get from sick to settle because of the lack of oxygen. So we use painkillers and opioids. So we were talking about the morphine injection in the knee for severe pain that addresses the symptoms. We wanna use hydration. So get them to drink lots of water to increase the volume of their blood. Uh We want to also keep them warm for vasodilation. We want to avoid high altitudes because high altitudes tend to have a low oxygen level. Um And we want to avoid low oxygen levels. In general issue with opioids is they are highly addictive. Um The other thing we can use is something called hydroxycarbamide. So this stimulates the synthesis of fetal hemoglobin. So it's basically hopefully a form of hemoglobin that uh has a higher affinity for oxygen. So it takes oxygen on very readily and it doesn't really let it go very easily. So the logic is if you're holding on to more oxygen and not releasing it less chance that your red blood cells will become sickled. Um It also suppresses new blood cells being formed and neutrophil production. So, neutrophils are a type of white blood cell and because it's suppressing neutrophil production, white blood cells fight infection, you have an increased risk of infection. We can also use bone marrow transplants. So we can replace the mutated stem cells with stem cells from a donor that are not mutated. So those will then go on to develop into normal red blood cells only really available to younger patients and you have to be matched with a donor to be able to get these. Um so a little bit difficult to get. There's gene therapy as well where we're literally inserting a functional gene into the affected stem cells to try and reduce the effects of sickle cell that's not very readily available because it is very expensive. Um And then the last thing is the antibiotics. If you guys remember what we were talking about with the spleen, one of the roles of the spleen is to get rid of bacteria and produce white blood cells. So, if patients have sickle cell anemia, more likely to have a not very well functioning spleen. And so we give them antibiotics and all of their routine vaccination, the flu vaccine, they'll have the COVID vaccine. Um and that's to kind of treat the infections before they get the infections to prevent them actually getting an infection. Um And there's no real evidence of risk to health unless they don't take the antibiotics properly. Then there's a risk of antibiotic resistance. So we are pretty much at the end. We have one more question after this. Um But before you guys do that, please take a couple of seconds to fill in the feedback form. This is not for the uni um it's for me personally. So I'm gonna give you guys a couple of one minute to um fill in a feedback form and then we will move on to the rest of the lecture. It's very, very short, I promise you. Uh and I'll just have a look in the chat. So Ben says would drinking water not help reduce blood viscosity. Uh Yes, it does. It does reduce blood viscosity. So viscosity is like the thickness of the blood. Um If you're reducing the thickness of the blood, you're reducing the risk that these sickle cells will block a blood vessel and kind of stick together. So drinking water is a good thing in sickle cell anemia. And another question. Oh, do I have a link for the feedback form? Uh Yes, let me put it in the chat. Give me one sec everyone. OK. So here is, here is the link for the feedback form. Um And please all fill it in. I know that it's been a very long time. Um But there are quite a few of you here and it is very important to get responses for this. So please do fill it in. OK. I'm gonna move on when um we've had at least 40 responses at the moment. We're on 22. So please do fill it in. Uh Could a blood film not be used for diagnosis? Yeah, it, it definitely could. I'm sorry that I didn't put it on the diagnosis side. Yeah, absolutely. Blood film is an important part of diagnosis. Uh This is a good opportunity. If you guys have any questions, please ask. OK, we are very almost um at 40 responses, the the average time for response is 50 seconds. So I can do this guys. OK. OK. We are at 40 responses. Thank you very much. Please keep filling in the feedback form. It is very important. Um But we will move on to our final mentee. So what is the mechanism of absin of hydroxycarbamide? Does it stimulate fetal hemoglobin synthesis? Suppress reticulocyte neutral production? Does it replace mutated hematolytic stem cells with cells that are not mutated? Does it supply functioning reticulocytes or does it use viral vectors to insert the nonmutated gene into hematolytic stem cells? Ok. Yeah, everybody got it. Right. Exactly. So, it stimulates fetal hemoglobin synthesis and suppresses our reticulocyte and neutrophil production. Great. So I'm not gonna go through ta guidance um because it may have changed and we are running a little bit short on time. But this is what we have covered. We've covered structure of adult cell hemoglobin. We've struct, we've covered the structure of sickle cell hemoglobin. We have covered electrophoresis of sickle cell anemia, blood film analysis, which is an important point uh of diagnosis. We covered the symptoms, the diagnosis and management as well and we have not covered ta guidance, but you guys will get the slide. So feel free to go through. Um I'm also very happy to put my email in the chat if anybody has any further questions, but I'm gonna go back to the feedback form. If you guys haven't filled it out, please, please please do. It's very important for me. I can see that is how many people there's 91 people and 46 have filled it out. So please continue filling it out. Um I'm gonna that is the end of this lecture. I'll go through some of the questions that are still in the chat. Um And I'll also put my email in the chat. Mhm If you guys would like to get in touch um and please feel free to email me if you have any other questions, I hope that you guys found it useful. I'm sorry, that was a lot of information. Um but it is quite a lot to cover. So feel free to email me if you've got anything else. Um ok. How does cold worsen sickle cells? So when it's cold, your red blood ves your blood vessels vasoconstrict. So the radius of the blood vessel gets smaller. And so when you've got a smaller radius to try and move through, it's more likely that your red blood cells will get blocked and create a blockage. And because there's a blockage, you're not getting blood supply to the tissues and that can cause low oxygen. So, ischemia and infarction and that kind of thing can cause pain. So it's not necessarily that the cold itself causes more sickling, it's that the cold can cause more symptoms. I hope that makes sense. Carolina. Um Ben says what was hemosiderosis again? So, hemosiderosis is just when you get too much iron and it deposits in your tissues. So that can happen if you have lots of blood transfusions because the body doesn't really have a way of getting rid of iron. So we have to be really careful to make sure that we give medication to try and reduce that iron. Mhm. Ok. I'm glad you guys found it helpful. If you have not yet filled in the feedback form, please do. Um And if anybody has any other questions. I'm happy to stay on for a little bit longer and answer questions if it's about CSI, if it's about med school in general, feel free. Um But if not, I'm all done with the lecture. So you guys are more than welcome to go when you filled out the feedback form.