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Summary

In this educational session, medical professionals will have the chance to delve into both blood cardiology and respiratory topics, as well as engage in SBA quiz questions covering hemostasis, lung function, the cardiac cycle, and more. This session is also special as it kicks off with a comprehensive overview on the cell cycle and basic biochemistry, highlighting the cell's cytoskeleton, the role of cyclins and CDKs in cell cycle regulation and cancer, and the study of action potentials. Your active participation is encouraged through polls, making this session both informative and interactive. These topics are fundamental to practicing medicine and will be revisited throughout your medical career, making this session an excellent opportunity for in-depth learning and knowledge reinforcement.
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Learning objectives

1. Understand the organization and function of the cytoskeleton, including the roles of microfilaments, intermediate filaments, and microtubules. 2. Comprehend the phases of the cell cycle, including associated regulatory mechanisms and checkpoints. 3. Understand the role and importance of cyclins in the regulation of the cell cycle, including the function of the P53 protein in preventing the progression of damaged cells. 4. Be able to explain the process of an action potential, including the stages of depolarisation and repolarisation. 5. Understand the concept of the relative refractory period in action potentials and its physiological significance.
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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.

OK, so, hi, I'm I'm Nicole. So today I will be covering topics related to blood cardiology and respiratory. And I've also prepared non SBA questions for you guys to answer and the SBA S will be on hemostasis, lung function, the cardiac cycle and the EC GS I'm really sorry. Um I think I was meant to be um the first speaker on cell cycle. Is that right? Sorry, Nicole. I don't, I don't mind you doing first. So would that be OK? Sure. Thank you. It's so sorry about that everyone. Um You had a little preview of what's to come. So yeah. Uh I hope you can see my screen. I'm just gonna make this powerpoint a bit larger for us. OK. Is that OK? For everyone? Brilliant. Sorry about that Nicole. Um So yeah, I'm Eliza, I'm gonna be going through some cell cycle um and basic biochemistry tonight, um these slides were made by Aisha but I'm gonna be delivering them for her. So off we go. So our first question, the cytoskeleton is a dynamic protein filament network that connects nuclear membrane plasma membrane and many organelles, one component of which is made of only actin and stabilizes and determines the cell's shape. So which of the following is this component? So a pole will be launched. Now guys, and just take a couple of seconds to um try up through this question and then we'll go through the answer. Perfect. Lots of answers coming in. Well done. A couple more of you and guys, your answers are anonymous. So please do um please do vote cos we can't see any is gonna help you. OK. So if we close that pole then brilliant. So most of you went with D and that is indeed the correct answer. So if we just look at the cytoskeleton compartments, you've probably seen this a lot in lectures and tutorials. Um But the cell has something called a cytoskeleton. Now, this is a structure and it helps the cell maintain its shape. So we can see we've got the microfilaments, intermediate filaments and microtubules. And these are kind of providing mechanical strength and support to enable the cell to carry out its function. Um And this is really important for things like division movement and it's different to the cytoplasm. So the cytoplasm is a general term for kind of everything inside the cell. Um But the cy the cytoskeleton is just interwind within the cytoplasm. So you can kind of picture it a bit like some threads and weaves throughout the cell. And there are three main types. So we've got the microfilaments, intermediate filaments and microtubules. So the microfilaments and microtubules are very similar. They're both very dynamic and relatively flexible. But we can see the microfilaments are, they're made of actin and they're outside of this. He so they're providing more structure whereas the microtubules are made of tubulin. So that's a really key difference knowing what these different filaments are made of. And then that will help you to remember what their function is within the cell. So the microtubules are within the cell, they're involved in mitosis, they're pulling those paired chromosomes apart during anaphase. And then last of all, we have our intermediate filaments in the middle there. So they're different from the two and they're more static. So they're involved in maintaining the cells integrity. So if we go back to our question, we can see um the correct answer is microfilaments. And we know that because it's, we know it's not cytoplasm or the cytosol as they're completely different components. They're not part of the cytoskeleton. And cytoplasm is just the general kind of region or term men for everything within the cell. And the cytosol is the actual fluid component. So then we know it's gonna be our microtubules, our microfilaments or our intermediate filaments and we need to pick the best one. So microtubules are made of tubulin, which is a different type of protein, not actin. So we know it's not microtubules, the intermediate filaments are a variety of other proteins. So that just leaves us with the microfilaments and therefore, that's our correct answer. So, really well done guys to those of you who got that. OK. So question two, the cell cycle is mediated and regulated by a variety of cyclins and Cyclin dependent kinases or CDK S. The expression of these mediators are regulated by genetic and epigenetic mechanisms. But in some cancers, these mechanisms are dysregulated and can cause unregulated cancer cell proliferation. So which Cyclin is responsible for regulating the G two phase of the cell cycle. Again, guys, the pole will be launched and just give it your best, best shot. It really doesn't matter if you get it wrong. Um Dis triumph and then we'll go through the answers again. I know this is a bit of a tricky question. Um We'll go through, we'll go through it in a minute. We'll give you a couple more seconds to get these last answers in. But this is just kind of something that you just need to learn really? OK. So if we finish the po there, so the correct answer was Bs Cyclin. So we'll go through this now. So there are four main phases in the cell cycle that you need to know. We've got our G one S phase M phase and then G two. So G one and G two, you can remember there is growth one and growth two and these are growth phases. So this is when the cell is increasing in size, we're making sure there's enough components for division. We're preparing the cell to split into two, the S phase stands for synthesis. So, so you can see that that's where DNA synthesis is happening. So that's where we're concerned with replicating our DNA, making sure there's enough DNA to then be split into two new cells. And there are three stages together known as interphase. So G one S phase and G two are all um within that first phase of um are all within interphase. OK. Then we move on to m phase. So that's standing for mitosis and that's separate from the other three. So, mitosis is the actual splitting of the cell. Ok. Um You might remember this from a level biology. It's very similar but just a bit more detail. So, mitosis is the actual division and we know we have prophase and that's where the chromosomes condense. We then have metaphase, which is when the chromosomes along a line up along the center. And we can remember that with metaphase and middle. So that's when all the chromosomes are aligning in the middle, we then have anaphase, which is then when the microtubules condense and they separate and they're getting pulled apart. So you can remember that anaphase they're getting pulled apart. Um And then finally, we have telophase and that's when the chromosomes are de condensing, they're unraveling the nuclear membranes are forming. And then last, but not least we have our cytokinesis. So that's when the last stage, our cytoplasm is cleaved and then we have two separate identical daughter cells. So, mitosis remember is producing identical cells. And then after mitosis, we have those two cells and they both enter through the cycle again. So they both start on their growth phase one, then the synthesis stage growth phase two. And then finally, mitosis. Now you can see on here, you've got some checkpoints. So it's really important that when we're um when the cell is dividing, we're preventing any hiccups, we're preventing any deformities or mutations. And these um checkpoints are mediated by something called cyclins. So CDK S now, the most notably is if there is any DNA damage, we have something called P 55 p 53. OK. The P 53 protein, um what this does is this is important in blocking the cell cycle from continuing. So if it's spots that we've um the cell has gone into s phase, it's replicating its DNA and there's been a mistake. OK. RP 53 will identify that mistake and stop the cell cycle from continuing. So we, we don't go into growth phase two and we don't go into mitosis. So it's stopping that cell which potentially has mutation from going any further and that's really important. So at that point, the cell is checked and it might be er repaired and then it can re enter the cell cycle or if the change can't be corrected, the cell will be destroyed, so it won't be replicated. So we're not replicating any mutations. So that's really important. And it's kind of like a quality control process. OK. So then if you just look down at the bottom, right of your screen, at the graph, you can see the cyclins are present during different phases and some are in higher concentrations than others during each stage depending on what they do. So these are fairly easy to remember with which Cyclin controls which phase because it's named after the phase. So you can see our growth phase. One, Cyclin is controlling our growth phase, one phase. Our S cyclin, our growth phase, one S Cyclin is controlling that step between growth phase and since a stage making sure we've got enough um kind of cell body synthesized in order to enter S phase, then we have our S cyclin again, that's checking our DNA replication and then finally, our M Cyclin. So checking that the cell is ready to undergo mitosis. OK. So there's quite a lot to take on board. When you get the slides guys, there's lots of information in the notes as well. But this is something that you just kind of need to learn and get your head around and it's just remember it a bit like quality control and making sure we're not letting any mistakes or mutations be replicated and passed on. OK. So that was why we had a cycline there. Um just, you know, coming back to the question, it's just a matter of knowing which cycling is controlling which phase. Um So growth phase two, we have our S cyclin to go back. You can see growth phase two coming in here is gonna be our S cyclin that's responsible for our growth phase two. OK. You can see that on the slide just there. So it's just about learning which cyclins are controlling which phases. OK. Question three. What does the relative refractory period refer to when talking about action potentials? So action potentials, this is quite a big topic. Now guys, and you'll revisit this topic in lots of um kind of in lots of different themes as you go through medical school. So you'll come across this again and again um that if you can kind of get your head around this, now you're, you're in a really good position. So is it to do with our sodium channels being open? Our potassium channels being open or sodium potassium pump? So there's a lot going on with action potentials, but we'll go through it now. That's it. We got loads of answers coming in. We're done a few more seconds. Again, it's completely anonymous. So please put yourself out there. Have a game. OK. Brilliant. So and that pool there, right? So the correct answer is C so potassium channels are open and the action potential can be fired again. So why is that the right answer? So you can see with the action potentials, there is a lot going on. So starting off down here with the graph, we have something called the resting potential and this happens at around minus 70 millivolts. So here there's nothing really going on. Um we're nice and relaxed, but there might be some kind of stimulus coming on and as we get increasing stimulate, so these are maybe electrical impulses being sent, we have this increase in voltage within the urine. Now, as we get more and more stimuli. So again, through those electrical currents, the voltage increases further. And we can see eventually it gets to about minus 50 or minus 55. Um at this point, it's something called threshold potential. Um It's important to note that for different neurones, the the threshold might be different. Um But generally, you can remember it is about minus 50 minus 55. And at that point, it means you've suddenly flicked that switch, you've got enough um voltage um to trigger an action potential, say what happens. So we've reached our threshold potential and now we're gonna go into depolarization. So the sodium vol the sodium ions, sodium voltage gated channels are gonna open and that's gonna allow our sodium rons to enter the cell. Now, we know sodium ions are positive. So we're gonna carry on increasing the voltage within that neuron. OK. So because they're voltage gated, it means that they open or close depending on the voltage. So once we've reached our threshold minus 55 you've got enough voltage to open the sodium voltage gated channels. So they're gonna open, our sodium mines are gonna have a rush in that positive charge is coming in. So we're gonna increase that voltage further. OK. And that phase is something called depolarization. OK. So the sodium ions are continuing to come in, we're getting a higher and higher voltage and eventually we're gonna reach about plus 30. OK. So it's gone from minus 55 minus 50 threshold to plus 30. So really high. And this is when um the urine is completely depolarized and that's something called the absolute refractory period. Now, I'll come back to refractory period in a bit. But once we get to that plus 30 we've reached that absolute refractory period. OK. Now, at this point, again, the sodium voltage gated channels are voltage gated. So when we reach this voltage, they're gonna close. So the sodium um channels close. So the sodium can't come in anymore. And also at that point, our potassium ions open. So we have our sodium voltagegated channels closing and our potassium voltage channels opening. And that means that because the po potassium channels are now open, our potassiums can flow out. Now, potassiums are also positively charged and they're gonna be flowing out of the urine. So if we have a positive charge leaving, it's gonna effectively bring the voltage back down and that decrease in voltage is called our repolarisation. OK. So we'll just go through that. But again, cos it, it is a bit tricky to get your head round. So we've got a resting potential. Everything's nice and relaxed. But you get some stimuli coming in, we increase that voltage to about minus 50 minus 55. We reach threshold at that point, our sodium voltage gated channels open and sodium ions can rush in making that urine more positive. And then they keep coming in, keep coming in and keep coming in until we reach plus 30 which is that absolute refractory period. And then the sodium voltage gated channels closed and the potassium channels open. So now we have our potassium channels open, potassium ions can flow out and because they're going out, our voltage is dropping, OK? And that's our repolarisation. We're coming back down to that negative voltage. OK? That's our repolarisation. So they're gonna keep going out and they're actually gonna pass that minus 70. They're gonna keep going down um because we've got something called leaky potassium channels. OK? And these are always remaining open. So potassium irons continue to leave um even when we've got that voltage below the minus 70. So it can actually drop down to about minus 90. You can see there and that's called hyperpolarization. So the membrane is completely hyperpolarized and that's our relative refractory period. OK. And then finally, we can see it's just leveling out to about minus 70 again, that nice relaxed um the kind of state of the neurine there. And that's from our sodium potassium pump returning that um electrochemical um gradient back to normal. So I was spoken a bit about refractory periods. What are they? So we've got two main types. So we've got that absolute and then we've got the relative. So the absolute refractory period is when we can definitely not have any more action potentials fired. So no matter how strong the stimulus is, we can't get another action potential. All the sodium channels are closed. But the relative refractory period isn't when we can get another action potential if we have a strong enough stimulus. So the threshold potential is still lowered, but we could open some voltage gated channels if we have a strong enough stimulus. So all we need to really remember is the a refractory period. We definitely can't have any more action potentials. All the channels are shut. The relative refractory period is when if we have a strong enough stimulus, we could then get another action potential, but we have to have a stronger stimulus. OK. So I hope that makes sense if we go back to our question was asking us about the relative refractory period. So the correct answer was the potassium channels are open and an action potential can be fired. So it's a bit vague and tricky to understand. But that's kind of, you know, the trick of the SBA S you just have to pick the single best answer. Um So the key bit is whether an action potential can be fired and in relative, it can be fired. So we can have an action potential. So we know it's ac or E OK, then the answers don't really um aren't really about the channels. We, we need to come back to its potassium channels being open and that's what's allowing us to get that action potential. So remember it's the leaky potassium channels. These are the ones that are always still open and they're the ones allowing the potassium s to, to diffuse out of the urine and get that action potential. So I hope that now makes sense. Again, it is a bit of a tricky concept that what I would say to do for revision, just try and talk yourself through this diagram. Understand when um channels are opening, when they're closing, what level the urine is at what voltage we need. Um And then again, about the refractory periods, all you need to know absolute. We can't have any actual potentials relative we can if the stimulus is strong enough. Ok. Question number four. A girl is running a long distance marathon and begins experiencing pain in her legs. She stops for a second to catch her breath and after a few deep breaths, the pain goes away, she continues running and after a while begins to experience the same fatigue in her muscles. So what's causing the muscle pain again. Hopefully we'll get a pole launch there. Perfect. Lots of really good answers coming in. Why don't guys you know this topic? Well, clearly you have a few more seconds. The last, last few of you to enter again. I can't see who's answering what, but I'm really promised by the results we're seeing here. So I spent all. Wow. Ok. So I think we'll stop the poll there and most of you have gone with B and that is the right answer. So why is that the right answer? Let's have a look. So we have our aerobic and anaerobic respiration which we're gonna talk about. Now, s the key things to take away from this side is that both aerobic and anaerobic respiration start off with glycolysis. OK? So both aerobic and anaerobic are gonna start off with glycolysis and that's the breakdown of glucose molecules into. Can anyone put it in the chart? What's glycolysis? Mm. Any ideas you can feel free to message me for? Ok. Brilliant. Thank you. Yeah. So glycolysis, the breakdown of glucose into pyruvate. Now, this doesn't need any oxygen. So this is all kind of anaerobic and it's happening outside of the mitochondria in the cytoplasm. But then we get the difference. OK. So in aerobic respiration, we have something called the link reaction and this occurs after glycolysis and the pyruvate is turned into acetyl coenzyme A and this is then fed into our TCA cycle or the Krebs cycle. And this is producing multiple products. But the main ones are N A DH and FA DH two. So reduced N AD and F AD and these are both substrates for oxidative phosphorylation, which is our last stage in aerobic respiration. OK. And eventually we're gonna get a build up of our ATP. And that's kind of the whole point of respiration to produce that ATP. And we've got a high yield there. You can see the energy yield of aerobic respiration is up to 38 A PS. OK. So 16 for each pyruvate molecule. And you can see we need oxygen because oxygen um is needed in that oxidative phosphorylation. So it's accepting free electrons, it's the final electron acceptor. OK. And that's why this is an aerobic process. Cos we need that oxygen to pick up those electrons in that oxidative phosphorylation. And so the first glycolysis stage is happening in cytoplasm. But then in that aerobic respiration, the link reaction TCA cycle and oxidative phosphorylation are all occurring within the mitochondrion. OK. And the waste products we have from here are carbon dioxide and water. Ok. Now, pyruvate in anaerobic respiration, we're producing the pyruvate again from a glycol glycolysis. But instead of entering our link reaction, it's gonna be turned into lax and that's the main waste product of anaerobic respiration. Ok. So that's all happening in the cell cytoplasm. We don't go into mitochondria at all because it's all the anaerobic processes it's happening. So we don't have any oxygen present. So we don't have the link TC or oxidative phosphorylation because we're not gonna be making any of that reduced N AD or F AD for oxidative phosphorylation. So basically anaerobic respiration is put simply glycolysis. OK? Is glycolysis occurring and then we need to get rid of the primary va to do that. We're gonna make lactic acid. So, aerobic respiration, you can see it only makes about two ATP molecules. So it produces a lot less energy, but we use it because it's faster. It can be an immediate energy source if needed. So you can see in a question, she was running a marathon. Um She, she'd be producing that lactic acid because her muscles would be respiring anaerobically. So we're gonna be making pyruvate through anaerobic respiration that's gonna be converted into our Lactic acid and our lactic acid is gonna build up. Um And it's all to do with an imbalance in oxygen supply and demand. So when this girl is exercising, the oxygen demand is overtaking the supply. So we need, we're shifting from that aerobic stage to our anaerobic phase. Ok? And the muscles are using more and more anaerobic respiration. We're producing more and more lactic acid. Ok. So, lactic acid causes a drop in the ph of the muscles because it's an acid and this can cause um the ph for environment to change and it can cause this kind of burn. So some of you might have experienced it if you've um, done lots of exercise before, after taking some deep breaths. So you can see the pain goes away. So that's because we're having a better supply of oxygen when we take those deep breaths. So you can shift it back into aerobic respiration. You can start to clear some of that lactic acid. But then as you see, when she exercises again, the pain in the muscles comes back. And that's because again, we're going back to that anaerobic stage. We're producing more of that lactic acid. We're lowering that ph and we're causing that burn, there wouldn't be a build up of carbon dioxide. Um because that's the byproduct of aerobic respiration. And we know in this, in this instance, she's using anaerobic respiration. So we're getting that lactic acid produced instead. Ok. So in this situation, you know, I could understand why some of you went with carbon dioxide build up, but because she's gone into anaerobic respiration, the better answer here is lactic acid. Ok. Next question, a baby was born at 28 weeks gestation and had to be kept in the neonatal intensive care unit for a few days. For observation. During this time, the nurses had to administer an amino acid supplement, which one of these could it have been. So, again, amino acids, these are a nightmare to get your head round. And that's something that you just have to learn but give it a go and if you don't know, just have a guess and then we'll go through. Yeah. So, really spit at the moment. Those of you who haven't uh submitted an answer yet, just, you know, give it your best shot. Uh Pretend you're in the exam and this has come up, you, you need to pick one, try and take an educated guess. If you don't know, that's absolutely fine. Cos these are a real nightmare, I think to get your head round. But we've got some ways to help you remember a couple more seconds. Very, very split. Uh OK, I think we'll stop the cold then. So unfortunately, the majority of you got this question wrong. The correct answer is actually cystine. So why is that? So we know we have 20 different amino acids in humans and these can be classified into three categories. We have essential, non-essential and conditional. So what does that mean? So essential amino acids means we can't produce them. Our body is not making them. So that means we need to essentially perceive it from our diet. It's essential that we take them in because our body can't produce them. And there are nine of these um and a good Pneumonic to help you remember is private Tim Hall. So PVT ti NH and sometimes you can put an A in there if you look it up ll so the A stands for arganine and that's um considered essential for Children but not essential for adults. So that might have been why um some of you chose Alanine for this question. Um We caught you out but yeah, Alanine is essential for Children, not essential for adults. So essential, our body can't produce them. So we need to consume it in our diet. Then we have our non essential amino acids. So these are the opposite. Basically, our body can make them. So we don't need to be taking them in from our diet because our body can make them for us. And then finally, conditionally essential. So we always have to have that one which is a bit more difficult to remember. Um So these are usually non essential but in certain conditions. So maybe if we're really stressed, if our um body is experiencing stress, so we might be ill or if we've had an injury um as well with pregnancy or as we increase in age, these amino acids become essential. So we start needing to consume in them in our diet because our body is no longer able to make them or not able to make them in sufficient quantity. So you've got a few there. So for, for the, for the amino acids, I would really just try to remember this a um this pneumonic pri ho to remember the essential ones. And then, you know, if they don't fit into that category, they must be non essential or conditionally essential. And again, you know, try to remember they're conditionally essential and also when they're conditionally essential. As you can see here, cystine is conditionally essential for preterm instance, glutamine for pregnancy, proline, severe physical stress, again, glycine pregnancy as well. And tyrosine in p phenylketonuria. So going back to the question, you can see again is this is something that you just need to learn really. So it's an um a conditionally essential amino acid. Um It's for preterm um infants. And so that could the correct answer. There was cystine again. Alanine was there to kind of catch you out. Um That's, that's um considered essential in Children, not adults, but a cystine is um uh so often given as a supplement to preterm babies. Um and it's usually given through an injection. That was a tough one though guys well done to anyone who got that one right? Ok. Coming on nearly at the end, a 27 year old woman has just found out that she is pregnant upon visiting the midwife for her antenatal appointment. She told the midwife she was recently having memory problems as well as headaches and blurred vision. When talking about her diet, she mentioned she doesn't enjoy eating vegetables, especially leafy greens. The midwife suspects the woman may have a folate deficiency weight of the following vitamins is the woman deficient in. So this is all about B vitamins and just learning, you know, knowing the names for um which is most of you are getting this. All right, whether or not you is lucky you guessing or you've learned it. But that's really good to see. I'll give you a few more seconds. So you've got a couple of keys in the question here. Um, she doesn't enjoy eating leafy green vegetables. So you can think about. Ok. Where is this B vitamin found? And you know, the midwife suspects the woman has a folate deficiency. So that's the real key folate deficiency anemia. Ok. Perfect. That's great. So most of you got that right. I think we'll end that call there. That's great. So, yeah, as many of you put the correct answer is E or B nine. So there are eight main B vitamins that we need to be aware of. Um I'll give you a minute to just have a read through this table. There's quite a lot of information here. So it might be worth just going through it in your own time when you have the slides. But the most important thing to be aware of is the different names. Um Also it's really important to know that the folate deficiency, which was spoken about in the question can lead to something called macrocytic anemia. So we said here, the, the midwife suspects the nurse has a folate deficiency anemia. So that's probably macrocytic and that's when the red blood cells are too large. So they can't carry out their function properly. Um And we know red blood cells are important in transporting oxygen. Also, it's really important in pregnancy because a lack of folate or B nine can lead to problems such as spina bifida. And this is when the baby's spinal cord um doesn't develop properly. So we have gaps in the, in the neural tube. Um and this is causing defects in the spine and or potentially brain as well. Um So it doesn't form properly. You'll learn about that more in case. Um it 78 to 9 next year when um um when you learn about um the fetus. But yeah, it's really important to remember for this one. It's quite a high yield fact that beeline folate is needed for um spinal cord development. And if we don't have enough of it or if pregnant women don't consume enough folate, um it can result in spina bifida. Um So yeah, I would say the main, main thing with this slide is learn the names, that's key really, you need to do that. And then if you can um learn about what, what's common with the deficiencies. So also, um you can see down here um about the pia for B3 niacin, that's, that's an important one to come up. Um So that's the trial of dermatitis, dementia and diarrhea and that's um often going to come up in a clinical context. So, be aware of that. Um Also important to be aware of vitamin B12. That's um mainly absorbed in the distal ileum. So we have receptor mediated endocytosis controlling that process. So firstly, we have digestive enzymes in the duodenum and these are gonna free the vitamin b12 from a protein. Um Does anyone know what that protein is? So we're talking about absorption of B12. So for vitamin b12 to be absorbed, does anyone know what it binds to? There are two answered that I'd be happy with for him. Any edges feel free to mess. Message me privately and the chat guys. So vitamin b12 intrinsic factor and haptor brilliant. Both of you got that right. Yeah. So firstly, our vitamin b12 binds to something called hapak that's gonna protect it. Um It enters and then that's freed um in the duodenum and then once that's freed, it's gonna combine with something else called intrinsic factor. Um And this is gonna transport the B12 and finally deliver it to the stomach's parietal cells. And then that complex of vitamin b12 and intrinsic factor can be absorbed. So, yeah, important to note vitamin b12 that's absorbed in the terminal ium there. OK. So final mind of that side, just have a read through, learn the names and learn about some of the deficiencies in particular B nine called spina bifida neuro two defects. So it's often advised to give to pregnant women and then also B3 can cause pra and that's the triad of symptoms there. And then finally B12 absorption, learn about how to an intrinsic factor. I would say those are the most high yield things from this page here. So going back to our question, yeah, the answer is just a matter of knowing the names. So it's a folate deficiency. And if you've learned from that slide, folate is also benign. So it's B nine deficiency, we're kind of giving you the answer there. Um So yeah. Uh again, they weren't eating leafy greens. That was another clue because folate is found in leafy green vegetables and that's the main source of Vitamin B9. So that's everything from me. Thank you so much for your attention. Really good. Um Answering. So keep that up for the rest of the session. Um And now am I passing over to Nicole? Yeah, that was brilliant. Thank you so much Liza. That was so well taught. So, yeah, it's Nicole up next. Sorry about getting the order wrong earlier, by the way guys. Thank you. Yeah. Thank you so much Lisa. That was really, really helpful. Hello? So now I'm going to share my powerpoint. I'll try it again. Are you guys able to see it? Not yet? Oh, I'll just share my screen. OK. Can you see my screen? Uh Yes, I think so. We can't. Yeah. Oh yeah, we can see your screen now. Yeah, we can see Power Good. So, hi, I'm Nicole today. I will be talking about different topics on blood cardiology and respiratory and I've made nine ba questions on hemostasis, lung function and the cardiac cycle and the E CG as well. So first off, I'm gonna start by showing you guys three hemostasis questions. So this is the first question. A 45 year old woman presents to the clinic with prolonged bleeding after a minor injury. Lab tests reveal a normal platelet count but a prolonged bleeding time which are following is the most likely cause of her symptoms. So I'm going to give you a few a minute to think about the answer. Oh, wait, sorry. I think I accidentally shown the answer to it. Super. So yeah, I'm going to give you a few more seconds. Um Nicole, we can't see the question anymore um because we, we we're sharing your kind of Yeah, because yeah, sorry, don't worry. So let's stop the pole there. And I think most of you guys have got the correct answer, which is c So before we jump into the explanation of the different options, I'm going to go through two very important concepts. So the first one is primary hemostasis. So it's when a blood vessels become damaged and the collagen of the blood vessel become um exposed. And Von Willebrand factors coming into contact with that collagen changes in shape, uh which enables platelets to bind to that Von Willebrand factor, those platelets which came into contact with the Vong Willebrand factor then changes in shape as well and they start releasing storage Granules which contributes to hemostasis afterwards. And for secondary hemostasis, it comes right after primary hemostasis. And it's when fibrin strands are formed to stabilize the soft clot from the primary hemostasis. And there are two models of fibro inflammation. So we have the classical model which is shown in the diagram on the left. So we can see that there's the intrinsic pathway, the extrinsic pathway and then they sort of join together to form the common pathway. And the second model is the cell based model which involves three stages. So the initiation stage, the amplification stage and the propagation stage. So, back to the different options. The correct option is C so Von Willebrand disease because the woman pre uh presented with a prolonged bleeding time, but there wasn't any changes in her platelet count. So it's very likely that her primary hemostasis was affected. So it's pretty likely that she has uh a defect in her Von Willebrand Factor. We have thrombocytopenia and that means a low platelet count. And we know that's not the correct option because the woman had a normal platelet count and the rest of the three options. So factor five laden disseminated intravascular coagulation and Antiphospholipid syndrome. These three different syndromes causes clotting rather than bleeding. And I don't think you guys need to know the specific um mechanisms of each conditions at your stage. But maybe from year three onwards, it's more important, you guys just need to know that these are clotting disorders rather than bleeding rather than conditions that causes bleeding. And Pfizer five laden is a genetic mutations which increase the chance of venous thrombosis or clotting in the veins does not directly affect primary hemostasis. And for disseminated intravascular coagulation, it causes widespread clotting and bleeding in, in different vessels in the, in the entire body. So it's very widespread. However, it's more, it's, it's more related to clotting rather than bleeding. And it does not typically, typically, typically cause a prolonged bleeding time. And for al Phos Lipid syndrome, it's when the immune system mistakenly uh produces antibodies against our phospholipids. And this causes a lot of clotting as well and might cause stroke, heart attacks, um pulmonary embolisms and miscarriages. So the correct answer is c so this is question two, which your following is the correct order of events in the cell based model for clot formation. So I'm going to give you a minute to think about the answer. Nicole, we've had a question in the chat which is, is um factor five, the clotting factor. I think so. Yeah, it's one of the clotting factors. I hope that answers your question. Reka and most people have gone for a, I don't know if you, oh, you can see the again. Sorry, I don't. And so most people have gone for eight and OK, so I think most of you guys have answered. So the correct answer is actually D so um A and D is actually very similar, but the wording is slightly different. So a it has initiation amplification and proliferation, but D has propagation and that's the correct answer. So I'm not going to go through different stages in the cell based model. So in the initiation stage, there's a very small amount of coagulation factors such as factor 27, nine and 10, which diffuses across the blood vessel wall from the lumen of the blood vessel into the surrounding tissues. And these factors uh becomes activated and they form the extrinsic pathway which causes a very small amount of thrombin to be produced. And when there's a damage site on our blood vessel amplification occurs. So, anti amplification is when a lot of coagulation factors becomes activated because of the damaged site. And then in the propagation stage, we have the eight A and nine A complex being formed. And this complex then binds to the negatively charged phospholipid surface of the blood vessel wall. And this complex then converts factor 10 to factor 10 A and then factor 10 A then complexes with factor five A which then also binds to the negatively charged phospholipid surface. And this complex between 10 A and five A then very efficiently converts factor two to factor two A and then this leads to a large amount of thrombin being produced. And therefore, this phenomenon is called the thrombin burst. So lots of fibrin strands are being formed which then stabilizes the soft clot being produced in the primary hemostasis. So this is actually a very tricky question. There's a slight change in wordings, but it's very important for you guys to remember three stages of the cell based model. OK. So let's move on to question three. So a seven year old boy presents with a history of prolonged bleeding episodes. So lab tests review a decreased level of factor eight activity. So which condition does this boy have? OK. Let me check the pole. So mostly you guys have answered A and some of you guys have answered B OK. So I'm gonna give you a 10 more seconds maybe. OK. So the correct answer is actually a. So most of you guys have got it right. So before we actually go into the different types of hemophilia, we need to understand the classical model of blood clotting. So I've, as I've just said, there's the intrinsic pathway and extrinsic pathway and then they both combine to form the common pathway. And from this diagram, we can see that hemophilia A actually affects factor eight and hemophilia B, effect factor nine and then hemophilia C effect factor 11. So factor 10 was skipped. So how remember this is hemophilia A? So A is the first letter and it affects the smallest number of clotting factor in terms of its number. So A affects eight and B affects nine and then we skip factor 10 and then see effect factor 11 and this is the definition for each hemophilia. So yeah, hemophilia A and B presents with very similar symptoms because they are relatively severe. But hemophilia C presents with a slightly less severe presentation compared to hemophilia A and B. OK. So let's move on to questions on lung function. So for question four, we have which of the following scenarios cause a VA VQ ratio to become infinite. I'm gonna give you guys a minute to think about this. Ok? So let me pull. Ok. So it's very split between A and C. So let me go through the answers for this one. So the correct answer is actually C and before we jump into the explanation of different options, there is a very important um concept that we need to understand which is the, the over Q ratio. And that's basically the amount of air entering the alveoli divided by the amount of blood flowing into that certain alveoli. So BT ratio can range from infinity to zero. So this can be easily understood by substituting different numbers into the equation V over Q. So when there's no ventilation at all, so no air going into that certain alveoli V will be zero and Q will be could be any number, so zero over any number equals to zero. So when there's poor ventilation, the ratio would come out as zero or less than one. But if there's no ventilation at all, then the ratio would be zero but if there's a blockage in the blood vessel supplying the alveoli, then Q would be zero and V could be any number. So any number divided by zero would be infinite. And therefore this ratio could range from zero to infinite. But in ra in reality, it's pretty rare to see complete blockages. So patients usually present with three different scenarios. So in a well ventilated alveoli, the VQ ratio would be al W will be one. So one is the optimal number for ra A VQ ratio because ventilation and perfusion is equal. However, in a poorly ventilated alveoli, the V will be smaller than the Q which then come out as smaller than one. And if there's a blockage in the blood vessel, uh or a partial blockage, then V will be larger than Q. Uh which means a VQ ratio would be larger than one. So anything that's not one, it's relatively suboptimal. Ok. So in a complete lung obstruction, there's no ventilation going into the lung. And so the alveoli wasn't well ventilated and therefore the equals to zero rather than infinite. And for lung fibrosis, it's similar to complete lung obstruction. So, so when there's lung fibrosis, lung tissues become scarred and stiff, some of the smaller airways becomes collapsed. And therefore, this causes a reduced or zero ventilation. And when the ventilation is reduced, um the VQ ratio would be smaller than one. And for pulmonary embolism, which is the correct answer. It's when a blood clot, it goes from the deep veins into the lungs and blocks one of the pulmonary arteries. And this blockage causes um the perfusion to be gone from that certain alveoli and therefore, ventilation over zero equals infinite. So, c is the correct answer. And for severe bronchospasms, ventilation is affected. So, ventilation, I is reduced or become zero. So it doesn't equate to BT ratio being infinite. So it's not the correct answer. And for pulmonary edema, it's when our lungs, the alveoli is filled up with fluid and this impairs gas exchange because the diffusion distance becomes greater for oxygen and carbon dioxide to go to the blood and carbon dioxide to leave the blood. So this reduces ventilation and might even cause the ventilation to become zero. So VQ ratio might be reduced or become zero. The so for question five, which is which of the following best describes the boars effect on oxygen binding in the lungs. So think about the oxyhemoglobin dissociation curve and the key word in this question is lungs. So lungs is a very important word in this question. OK. So that's about a minute. I'm gonna check the pole. OK. So, so some of you guys have answered A and C and B as well. 10, so let me go through the answers. So the correct answer is actually b so a portion of you guys have got this question correct, well done. And before we jump into the different options. You guys need to understand a very important concept, which is the oxygen dissociation curve. So in in the center, we can see a red line and that's the normal for oxygen dissociation, it can either shift to the left or to the right. So when carbon dioxide pressure decreases and when Ph increases it, this causes the graft to shift to the left and when the opposite happens. So when carbon dioxide pressure increases and Ph decreases, it causes the o oxygen dissociation curve to shift to the right. And this is really important for the offloading and loading of oxygen on hemoglobin. So when the hemoglobin reaches the lungs, as we know, as we know that the lungs is, the lung is a very important organ for ventilation. So in the lungs, it has a relatively low carbon dioxide pressure because it's where gas exchange occurs. So, compared to the peripheral tissues of our body, the lungs is relatively well ventilated and therefore it has a lower carbon dioxide pressure. And when the carbon dioxide pressure decreases, it causes the ph to increase because the lung environment is a lot less acidic. So it it has a relatively high Ph and a higher ph causes the graft to shift to the left. So as we can see from the graph in the previous slide, when the graft shift to left, the gradient of the blue line is actually a lot steeper than the gradient on the right on the right. So the GRE the blue line is a lot steeper than the green line. And that means uh the affinity between the oxygen and the hemoglobin is actually stronger when hemoglobin reaches the lungs. And this helps with the loading of oxygen onto the hemoglobin. As hemoglobin passes through the lungs and as the hemoglobin and oxygen goes into our peripheral tissues, um the affinity between the hemoglobin and the oxygen becomes a lot lower because of the right shifting of the graft. So from the graft in the previous slide, we see that a right shifting of the graft means that there is a weaker affinity between the oxygen and the hemoglobin, which causes offload the unloading of oxygen to become a lot easier. And therefore peripheral tissues are able to be um sort of oxygenated by the oxygen provided by the hemoglobin. And therefore the correct answer is b because when hemoglobin moves into the lungs, the lung has a higher Ph because it's less acidic, uh there's a lot less uh hydrogen ions being dissociated. So there's an increased ph in the lungs, decreased carbon dioxide pressure. And therefore, this causes the graft to shift to the left. So, and this increases the binding between carbon dox, uh not carbon dioxide, oxygen and hemoglobin for transporting. And so for question six, we have this question which is which your following best describes physiological bed space in the lungs. So we have a lot of different descriptions. OK. So that's about a minute. I'm gonna check the pole to see the results. So I can see that most of you guys have chosen C, a small amount of people who have chosen A B and E. OK. So let us check the answer for this. OK? So the correct answer is actually c so most of you guys have got it correct. Well done. So there are three very important concepts here. So for anatomical dead space, it means the portion of the respiratory system which is not capable of taking part in gas exchange. So it's the conducting airways, which includes the trachea, bronchi and bronchioles. And they have a relatively thick wall, which may, which means that they are not capable of carrying out um gas exchange. And, and however, they are responsible for transporting air into the spaces where gas exchange occurs. And then we have the functional dead space, which means that the alveoli itself, it's capable of carrying out gas exchange. However, there isn't enough blood supply in that uh alveoli. So um no perfusion in that certain alveoli, which means that even though it's capable of carrying out gas exchange, there's no blood going through that alveoli. So no oxygen was transported in that area. And therefore, it's a functional dead space. So it's capable of gas exchange, but because of no blood going into it, so it's functional, but it's dead. And for physiological deadspace, it's basically the combination between anatomical deadspace and functional deadspace. So it's the trachea, bronchi and bronchioles plus the alveoli that's incapable of carrying out gas change. Ok. So now let's move on to questions on the E CG and the cardiac cycle. Ok. So this is question seven, arrange the following phases of the cardiac cycle in the correct order. We have seven different steps. So try and arrange them according to the correct order. OK. So that's a minute. Ok. So I can see that 12 of you guys have answered the question. Um I'm gonna give you a few more seconds, 20 more seconds to answer your question. Ok. So I'm gonna stop the pull there. So I can see that most of you guys have answered E and a few of you guys have answered C OK? So the correct order is actually e so most of you guys have got it correct, well done and I'm not going to go through the different steps in the cardiac cycle. So first we have the atrial contraction, which means the atria on both sides of the heart contracts, which pushes blood into the ventricles. And then the next step, we have isovolumetric contraction, which means that the ventricles contract. However, the blood volume in those ventricles are haven't changed at all uh during this process because the mitral and the tricuspid valves are closed, which prevents the backflow of blood into the atria. And the third step is rapid ejection. So blood is being pushed from the ventricles into the pulmonary arteries and the aorta and the aortic and pulmonary valves are open. Next, we have reduced ejection and that's because of um most of the blood have already been ejected from the heart. And on the fifth step, we have isovolumetric relaxation. So the ventricles of the heart relaxes and the blood within that ventricle doesn't actually change in this process because the aortic and pulmonary valves have closed from the previous step, which prevents the backflow of blood from the pulmonary arteries and the aorta back into the ventricles. And then on the sixth step, we have rapid ventricular filling, which means that the ventricles are being filled up with blood even though the atria still hasn't contracted yet. And this is this can be due to gravity, um pressure gradient established by the atrial contraction during atrial systole. And at last, we have reduced filling, which means that the feeling of the ventricles have slowed down and this step occurs right before the next cycle begins. So, right before the atrial contracts. OK. So move on to question eight and the standard 12 lead E CG which you're following is the correct placement for the V one chest electrode. So I'm gonna give you guys a minute to answer this question. OK. So 10 more seconds. OK. So now I'm going to check the pulp. OK. So some of you guys have answered a uh most of you guys have answered. E some of you guys have picked A and D. Ok. So let me go through the answers. So the correct answer is actually Ed Sorry. So, um, so a lot of you guys have got it correct. Uh It doesn't matter if you guys have got it wrong right now. As long as you know it for is skis next year. Ok. So for the first chest lead, it's placed in the fourth intercostal space. So we usually would palpate the sternal angle, the angle of Louie and then we would move down three spaces until we've, we've reached the fourth intercostal space and right on the right, right on the right of the sternum, we have the first chest lead and then on the fourth intercostal space left of uh left of the sternum, we have the second electrode and then personally, I would place the fourth electrode first. So I would palpate the fifth intercostal space in the midclavicular line. So right in the middle of your clavicle, a vertical line drawn from the middle of your clavicle. And when it reaches the fifth intercostal space, that's where you place your fourth chest lead. And then I would place my sixth chest lead. So it's right at the, it's at the same level as the fourth chest lead and it's right in the mid axillary line. So in the middle of your armpit, so draw a line, draw a vertical line from the middle of your armpit, which extends downwards down your waist. And then once it reaches the level of chest lead, four, that's where you place your sixth chest lead. And then the third chest lead is right between the second and the fourth chest lead and the fifth chest lead is right between the fourth and the sixth chest lead. So I would place 1st, 2nd, 4th, 6th and then I would place 3rd and 5th at the end. So yeah, so D is the correct answer because it's fourth intercostal space on the right side of the sternal border. I know it's pretty easy to mix up uh second intercostal space because it's where you auscultate the heart. But for E CG, it starts off with fourth intercostal space on the right sternal border. OK. So this is the last question which of the following shows the time taken for atrial depolarization to reach the ventricular myocardium. So I know it's not very clear but on the E CG wave. So P wave QR S complex T wave which are following segment or wave displays the atrial depolarization for the time taken for atrial depolarization to reach the ventricular myocardium. OK. So let me check the P. So most of you guys have said B and let us check the answer. So B is the correct answer. So well done. Most of, most of you guys have got it correct. OK. So this is the E CG wave. So we have the P wave which shows atrial depolarization. And for the PR segment, which is between the P wave and the QR S complex, um it shows the depolarization of the A V node. So the atrial ventricular node and also the bundle of his. And for the cur complex, it shows the ventricular depolarization. And then the ST segment is also called the quiet phase, which is when all ventricular muscles has been depolarized and it's relatively quiet. And for T wave, it shows ventricular repolarization. And you might ask, where's the wave for atrial repolarization? And it's not shown in the E CG way because it's kind of buried in the QR S complex. So it's not visible. And yeah, and that's it for my presentation. And these are the references. Thank you for your time today. I hope you have a great weekend. Yeah. Oh And thanks Nicole. That was great. Um Should we take a two minute break? So some people can go and get a drink, stretch their legs or things like that. So if we start again at like in two minutes and then that'll be with Joe. Yeah. And Nicole, that was really, really good. Very, very informative. Thank you. OK. Brilliant Joe. Are you ready to share your screen and things? Oh, yeah. Yeah. Yeah, I am. Can you hear me? Yeah, we can now we can see the slides. Great. Thank you. OK. So today's session is gonna be on immunology, the kidney and the endocrine system, I'm Joe and these are quite big heavy subjects. So we'll just take it one at a time, see how it goes. First immunology. We've got some s we going to do an overview of the immune response. We're gonna cover innate immunity and also adaptive immunity. Ok. So, the lineage of immune cells, it all starts with this hematopoietic stem cell in the bone marrow. And it's going to differentiate into either myoblasts or a lymphoblast. These are precursor cells. The myoblasts are they going to differentiate into the basophils, eosinophils, ma cells or neutrophils. And these are your granulocytes. So these are cells that have contained Granules into the cytoplasm and they're gonna release enzymes, proteases histamine in order to cause inflammation and cause an immune response. There's also these monocytes here and they circulate in the bloodstream and enter tissues where they can differentiate into dendritic cells. Mhm. Keep it that way, macrophages. Ok. And these cells, they're important in bridging the gap between this innate and adaptive immune response. The lymphoblasts can differentiate into natural killer cells. T cells and B cells. These are called the lymphocytes and then your B cells can further differentiate into the plasma cells. And those are your antibody producing cells. You can think of the myeloblast image as more of an innate immune response side and also the natural killer cells there. And I know T cells and B cells, they are primarily your adaptive immune response. So a quick IV the response is nonspecific. All pathogens are handled in the same way. So anything identified as oneself is targeted and handled and the adaptive immune response that's very specific. So the response is specifically targeted towards the pathogen because everything is handled in the same way and the innate response acts quickly and occurs in hours. An adaptive response takes a long time. It occurs within days. There's also no memory formed in innate community. But there is a memory form adaptive immunity and that enables a rapid response to future infections in the same pathogen. Ok. Let's look at a community. So first, an FDA, a 23 year old male patient presented to an sti clinic with a one week history of dysuria and white penile discharge. A first catch urine test shows they have a chlamydia infection. Chlamydia trachys is an obligate intrasellar bacterium, which immun cell is important in destroying these infected host cells during the innate immune response. Is it a one second Marcel ba dendritic cell C A macrophage, da natural killer cell or EA B cell? I'll give you a couple of seconds to think, think about the roles of each of these cells, but we'll cover all of that as well. Ok. And the answer is it da natural killer cell. We'll go into what it is in a second. So there are different barriers in the innate immune response. We have physical barriers such as the me a escalator, the skin and mucous membranes that the cells are tight junctions present moving across them into the bloodstream, which have physiological barriers such as vomiting, diarrhea, coughing, sneezing. If you imagine a parasitic worm in your gut, vomiting and diarrhea, it can help expel a pathogen from your body chemical barriers such as an aesthetic ph in the stomach, the skin and in the vaginal canal. Great a very unfavorable environment of bacteria to grow in and also antimicrobial secretions such as in tears. Liver mucus also help propel pathogens. The microphor is also an important barrier and the microphor are all the microbes are naturally body. They prevent infection. They do this by blocking host cell receptors competing for nutrients and space. So, pathogens can't have it themselves and also they secrete their own antimicrobial factors. They also have nutritional benefits for us. They Vitamin K among others are, they are sort of opportunistic infection. So if barriers are broken, such as the skin, if you have a cut or if you immunosuppressed due to a medical condition, or even if the microflora introduced at different types where they usually grow, they can all cause infection. The cells in immune response. You have neutrophils. They're important in sis and antigen presentation. They kill pathogens and they do this by screening reactive oxygen species and prote like elastase and MPS or matrix metalloproteins. Macrophages. They're important in phagocytosis, antigen presentation and cyto concretion and close. And they're important because they bridge the gap between innate and adaptive immunity. They fs and spells and because the antigens on the surface and the inn immune response and they also activate naive T cells and lymph nodes. So they can become a effect to help the T and cytotoxic T cells. And that's the adaptive part. Basophils, basophils, mast cells and eosinophils. They're important in the destruction, multicellular organisms like helmets, which are the large pa worms. They are also important in allergic reaction. You kill yourself. This is the answer to the F ba. Their role is to destroy infected host body cells and cancer cells because chlamydia is an obligate intracellular bacterium. You need to be able to destroy these infected host body cells stop to stop the infection spreading. They do this by the release of cytotoxic Granules that can trigger apoptosis. Another F ba during an infection, macrophages, cytokines that promote information to help fight infection. What are some examples of proinflammatory cytokines? We've got TNF alpha A one A 10 TGF beta ale one il eight TGF beta ale one il 10 and TNF alpha il one il eight. I got one more T alpha. Aisle one, aisle six, I'll give you another couple of seconds to think and then we'll review the answer. OK, I'll end it there. The answer was E TNF alpha. Aisle one and aisle eight but half. You got it right. That's really good. So the solu part of the innate immune response, you got the complement. So this is a system of proteins that complement the immune system to more effectively clear the pathogen. Example, the C three B that's important opsonization. So that marks pathogens that could be more effectively vag sotos by the immune system. We've got C three A, four A and C five A, they're pro inflammatory and Oxin. So they trigger the male degranulation. You'll see in allergic responses. And C five B to nine complex, they're important in poor formation to cause cell lysis cytokine. These are signaling proteins used to communicate with immune cells and control information. So this is the answer to the, this is why the answer to the FDA was right. The examples we had was TNF alpha tumor necrosis factor, alpha interleukin one and interleukin six. They're all your proto the main ones, chemokines. This is the type of cytokines and they're used to recruit I mean cells to the site of information and an infection to help deal with those pathogens. Examples are il eight interleukin eight ICC one. So these recruit the immune cells, the site of infection rather than causing the inflammation themselves. Ok. So, antigen presentation and pathogen recognition. How does it work? These cells have P RRS which are pathogen recognition receptors. An example of these are to light receptors and R one like receptors. And I use these P RR to bind the pamps which are pathogen associated molecular patterns to help recognize these pathogens. So, how do immune cells present antigens where they can use an MHC class one complex uh intrasellar antigens. And these are present in all cells because all cells, all body cells need the ability to show to the immune system that they've been infected. And there's pathogens inside of them. They can also use M HC class two complexes. These M HC complexes are receptors that they present on the surface. And MHC class two complexes are important for extracellular antigens. And so they're present on dendritic cells, macrophages and B cells, adaptive immunity. Ok. Quick overview. It's made up of two parts. We've got cell mediated immunity. This is the immune response that mainly deals with intracellular infections. This involves activation of cytotoxic T cells and also you more immunity. This is the immune response that many deals with the extracellular infection and evolve the secretion of antibodies by B the patient contracts the measles virus, an intracellular pathogen that uses host cell machinery, synthesize new viral particles to kill these infected cells. Hytox T cells activated one cytotoxic T cells mm secret to make pores in the plasma membranes of these infected cells. It's a rectal ocean species. E ba C for enzymes d perform these. Can you under there? I write this performance. So we we'll go into the Why? That is a minute. So sell media to community. This involves health T cells. These have CD four receptors that bind the peptide MHC plus two complexes of antigen presenting cells. The role of health T cells is activate the cytotoxic T cells and other immune cells. Yeah, they have CD eight receptors and bind to peptide MHC class one complexes. They destroy host body cells that are infected with the pathogen C media immunity results in the formation of memory T cells. During reinfection, they can be activated directly by any antigen presenting cell and result in a quicker immune response. You don't get the dendritic cells bridging the gap of, of innate and adaptive immunity. So it's much more quick. How do you remember which T cell binds to? Which peptide MHC complex? This is a bit more, this stuff is a bit more complex. But I think it's still good to learn. Anyway, the CD four receptors are for the class two complexes and the CD eight receptors on the cytotoxic T cells after the class one complexes. And if you multi supply both numbers together, you should always get eight. So the CD four links up with the two, four times two is eight and the eight linked up with the 18 times, one is eight. So this will explain the FDA, how do they call cell death cytotoxic T cell. We have perform that makes holes in the cell membrane. We have grand enzymes that cause DNA fragmentation to induce apoptosis. Ok. We have F ligand which binds to the fat receptor on the target cells to induce apoptosis. More than the T cell will activate the B cell percentage into plasma. And there are two signals required. The activation of the B cell T cell receptor may help the T cell bind to the peptide MHC class two complex on the B cell. The second signal is the CD 40 ligand on the health T cell bind to the CD 40 receptor on the B cell. Both these are required for activation. This results in a clonal expansion of antigenspecific plasma cells and the plasma cells initially only secret low affinity IBM. That's an an antibody that doesn't really effectively bind to antigens through processes of class switching. Somatic mutation in clonal selection, you'll get plasma cells high affinity antibodies. Despite resection much more efficiently, you will get memory B cells being formed. So during reinfection, there will be plasma cell proliferation and immunoglobulin secretion. Oh During breastfeeding, the baby received immunological protection through the breast milk to ensure that adequate protection. Whilst the immune system is still maturing. In addition to immunoglobulin, the breastmilk contains lactoferrin enzyme alpha la and case which I mean a globulin ice pack the day receiving during breastfeeding. Is it A I GM GG IG A I GDI GE? OK. OK. And the pool back the answer is IG A. So there are different types of antibodies or immuno coupling I GM. That's the first one to appear on the B cell surface and the first one to be secreted during the immune response that is found in the plasma IgG. This is the predominant immunoglobulin during a secondary immune response. They found in the plasma in the tissue ig that found secretions. That's the answer to the S pa tear, breast milk and gastrointestinal tract excretion ig This has receptors found in ma cell eosinophil for an allergic response is found on the skin, the lung epithelium and the gut epithelium. And the function of I GD is unclear. So that will, it's not too important to worry about. So how do they help fight infection? Will antibodies neutralize toxins? They activate, affect the cells, they call agglutination which sticks pathogens together. So they can be more easily. They activate the complement system which we talked about earlier and they're also important in optimization. So they bind pathogens to mark them. It could be more effectively hydros by I mean cell. Ok. A quick summary, the cells use pr to recognize pamps to fight pathogens. Adapt to immunity involves self mediated and moral immunity. Cytotoxic T cells group for enzymes and ligands to kill host body cells. There are different classes of antibodies and IG A found in secretion. And now we'll look at the kidney, the mellows, we're going to look at the anatomy, filtration, reabsorption and secretion. Quick, look at Ph control and also the ra uh let's look at the anatomy of kidney. The ureters are responsible for transporting urine from the kidneys to the bladder. There are three points to which the ureters are the narrower, which option describes these three points. The a the crossover of the common iliac arteries, the external uteral sphincter and the ureteral sphincter. B, the pelvi uter junction, pelvic brim SCU junction. Is it the pelvi junction crossover? Pelvic brim, the crossover of common iliac, the pelvic brim of the external sphincter or the pelvic brim s junction on the external sphincter. Mhm This is a pretty hard question. So don't worry about it. You get it wrong. Just give it a go. I wonder that the answer is the the pelvi uter junction, the pelvic and the Vesico junction. They have a picture of the, you can see the ureter is traveling down towards where the bladder is. Uh this metal and red here. But that's the aorta divided to the common iliac arteries to here is the first point where it's the narrowest. And that is the p of the uter junction here is where the pelvic brim is. So where the common, where, where the ureters cross, the common Iliac arteries at the same point, same level as the pelvic brim. So those two positions are the same. And here we have the ves junction and clinically significant because it's the three places where renal stones come lodged in there. So renal stones are most likely gonna get stuck. These three position, we have a renal cortex, which is the outer part. And the renal ella, which is the inner part and adula is organized into these structures called pyramid. Yeah, the whole thing is encapsulated within the renal capsule. We have columns here which are the projections of the renal cortex which lead into the renal sinus. As a of the renal pyramids. We have renal papis which drain into minor caly and many different m minor or major calyx and several different major on the renal pelvis, which is where the urine can then be transported through the router into the bladder. You have the renal vein and renal artery for the blood supply and the ureter vein and artery. They thought the hilum of the kidney. Here is the picture of the nephron, the renal corpuscle, the glomeruli inside we go and get the proximal tubule. These, these, these are both in the cortex, then dive down into medulla with the loop handling and then back ups the cortex. The distal convolution tubule, it's fine when you have the collection back here. Mhm Yeah. So ultrafiltration is a picture of the glomeruli with the afferent arterial with blood coming in an efferent arterial blood coming out, the letter A becomes before e in the alphabet. But I remember efferent afferent comes before efferent. This is capsule. Here we have podocytes surrounding the epithelium that ended dealing with the cap cells. Ok. So the afferent arterial dilates and the efferent arterial constrict. This creates a high pressure gradient. The capillary. And the gomera is demonstrated, the endothelial cells have small holes in them that you can see in the picture down the bottom. No small holes in the fenestration podocytes are specialized cells which also the capillaries. And they have processes which have gaps in between filtration flips. And all these gaps of filtration flip mean that water and small solutes like amino acids, glucose sodium can be forced out to form a filtrate. Whereas large proteins and blood cells have to remain in circulation from a quick definition of osmolarity and osmolality. So osmolality is a. So kilogram of. So solvents measure the mill osmos per kilogram and osmolarity. So per liter of osa, the important thing to realize is the higher the hospitality or or hospitality, the higher the concentration of salty. So the higher the number of more salty the solution is OK. So we're gonna quickly go over the family in the ascending room, sodium is being pumped out of the tuber lumen into the insition to make a difference of 200 miller moles. See here, 300 to 106 104 100 we've created a difference of 200 water remains in the cheaper lumen because it's impermeable to water. So that's why I pour the sodium out of the cell into the in in the thin ascending. This reabsorption is passive through these channels here FC or sodium channels. Whereas in the thick ascending limb it's active. Do you use ATP, this creates a concentration grade in the medulla where it gets salty as you go down the position. You can see the osmolality is increasing as you get deeper and deeper down in the medulla. Yeah, the fluid arriving from the PCT is about 300 miles miles and it keeps encountering interstitial with a higher and higher osmolality. So water will move out into the position. I was at the same down here and it does it until the two of moralities equal. So you can see your 300 comes to 300 the 300 then lose water to become saltier and reach a value of 600 so on. Its maximum concentration down here. And then this fluid here when it reaches the ascending limb is gonna start losing the sodium just like up and back at the start of the cycle. This means the kidneys can re absorb about 99% of this filtered water. How does this sodium reabsorption happen? Well, there's a sodium potassium 80 pas on the basolateral membrane. And this pumps three sodium out of the cell and brings two potassium into the cell. These are cells lining a thick ascending limb. This means there's a low concentration of sodium within the cell. And also because you've lost three and only gain two and only gain two potassium, you also have a low relatively low electrical charge. So you create electrochemical gradient and that means sodium can diffuse into the cell along with potassium and chlorine via this transporter. Here, N KCC two along with potassium and chlorine prevent this build up of potassium inside the cell has to be transported out to be lost within the urine. I notice this by wrong case using ACP. So it can then be lost within the urine. Water does not leave this this thick extending limb into the tubular lumen because it's impermeable to water. So water cannot follow, cannot be reabsorbed. The result is you get a sodium reabsorption from the tar lumen to leave a tubular fluid with a lower osmolality position. When you get the slides, you can look back at the previous diagram just to make sure this all makes sense because it's, it's quite confusing. And if you're interested, this is the transport here inhibited by loop acting diuretics like furosemide. Um There's lots more slides that I put here detailing the specific transport within a different part of the Nephron. But it would take a long, long time to go through right now. So you can take a look at it in the slides. Once you get them antidiuretic hormones are essential for water reabsorption in the Nephron. In diabetes insipidus, there is a decreased relief or response to a DH when the ne on a DH act on. And what do you predict the urine osmolality will be like in diabetes. And syphilis is act on a PCT high urine o efferent arterial high urine, late DCT and collecting ducts, low urine formality, ly, low loop urine normality and glomeruli lo to think about where a DH acts on in the Nephron and then don't be thrown off by, by term. As you might have heard before, like diabetes insipidus, you have a decreased release response to a DH. So what do you think this will make the urine like? Ok, so the answer is, see we're going to Hawaii. So yeah, it acts on a DH act on the DCT and the collecting ducts. And so in, in normal, normally, ADH causes water reabsorption. And so if you have less ADH get less water reabsorption and more water excretion. If you're losing more water in the urine, if you're losing more water, you have a very dilute urine which is low concentration of solutes, which means low osmolality. OK. We can look at a DH. Now. So the goal of ADH is to raise BP and to decrease plasma osal it uses in two ways. It causes vasoconstriction by binding to vasopressin type one receptors on smooth muscle in blood vessels, it's called this constrict, the blood vessels. So you increase the BP and also I to A DH binds for vasopressin type two receptors on the principal cells of the late DVT and collecting that intrasellar signaling leads of vehicles containing a four and two channels being transported to the apical membrane. And these are four and two channels allow water reabsorption in the principal cells and then water can then move out of the cells into the bloodstream to increase the volume of the blood, to increase the BP. Ok. Because of you, the PCT, the PCP is when most things are reabsorbed. So 65% of the water and 65% of the different ions are reabsorbed. All of the glucose is ab all of the amino acids. It also secretes things like organic acid bases, protons and also drugs and toxins that build up in the blood. The loop of henley that's responsible for absorbing about 25% of the sodium. Also reabsorb water and other iron, sodium chlorine and calcium. In the early DCT. We also have the which which we'll talk about in a second, the late DVT and collecting duck back and forth more of the absorption of sodium chlorine water urea and also uh potassium and also the control. So the patient has an exacerbation of COPD over the past seven days. Their kidneys have been working to keep their ph in the normal range to prevent the doses. What buffer does the kidney manufactured, help excrete protons ensuring the blood ph stays within this range. Is it a ammonia? B phosphate C carbonic acid D bicarbonate or E sodium hydroxide? Give me a couple of seconds to think about that. And at your office down. OK. We're in the pool there. The answer is it's ammonia. So it's what does the kid manufacture. So you get bicarbonate reabsorption of PCT to help control top control VH you get a filtered phosphate buffer in a late DCT and collecting duct. So it's not being manufactured, manufactured by, by the um cells of the late collecting duct. That's why it's not the answer. And the ammonia is actually manufactured in the late DC and control the age that explains the FDA. There are a few small slides here on the different transporters involved that you can look at when you get to get the slides and we go to cover the R system, the running angio. So a runner does not drink for two hours during their race and they become dehydrated, run angiotensin aldosterone system helps to ensure that their BP remains high. What is the wrong to convert angiotensin two into aldosterone to convert angiotensin into angiotensin. One to convert renin into angiotensin. One, angiotensin, one, angiotensin two. I'll give you a moment to think and we'll talk about the outcome. Oh God, great. It seems like you got that right. The answer is to angiotensin one. Angiotensin two ace is angiotensin angiotensin converting. So the goal of re is to increase the BP and it's secreted by the er apparatus. In response to three things in response to low BP, there are receptors and afferent arterial to detect a low BP. And it stimulates the apparatus to secrete its, we have reduced sodium. So, macular cells they're present in the DCT and they detect when there's a reduced sodium delivery. And the these then stimulated the apparatus to secrete their, also the sympathetic nervous system. These nerves stimulate the juxta apparatus to, to secrete renin. And they do this by the beta one adrenergic receptor. Here, you can see the macular den cells on the walls of the DCC just passing by the apparatus near the renal bri can also be inhibited by A NP, which is atrial peptide. And this is released from atria stretched. If there's a high BP, the atria are probably going to be more dilated and stretched out, release A NP and then cause an inhibition of renin. But let's look at the the system here. The re from the JG A angiotensinogen is produced in the liver and running into enzyme to cleave angiotensinogen to form angiotensin. One angio syndrome. One is then converted to angiotensin two by eight angiotensin converting enzyme which is the answer androgens two then can then cause vasoconstriction. ADH relief, increased synthetic activity, sodium reabsorption, potassium excretion and water retention and also aldosterone excretion from adrenal cortex. Aldosterone also causes sodium reabsorption, potassium excretion and water retention. The overall effect of these is to increase the BP and increase that sodium delivery in the DCT, which can then negatively feedback on in the loop to decrease running. That's an example of negative feedback. You've got a quick summary here. Of the functions of any. And for your so quick summary, there's an outer cortex and inner medulla. In the kidney ultrafiltration occurs become meralis, nephron motion, reabsorption of the kidney occurs in the PCT. In the LI family. Sodium was transported into the interstitial space to maximize water reabsorption, like distal converted tubule, collecting duct cells use phosphate and ammonia buffers to control Ph and the ra system is responsible for BP control. Ok. The last thing we're gonna talk about is the endocrine system. Some eos we have the hypothalamus and pituitary gland which will cover thyro gland, the adrenal glands. We'll take a really brief look at the reproductive hormones too. A 50 year old patient visits his GP with symptoms of fatigue and headaches and mentions they no longer fit into their shoes upon examination. The GP notices that they have an enlarged tongue and wide teeth. The GP suspects they may have an overproduction of growth hormones through which way does the hypothalamus communicate with? The pituitary gland secretes hormone is a, the pituitary neurovascular bundle B, the nerves in the pituitary stalk, C blood vessels and pituitary stalk. D the hypophysial portal system for e endocrine arterial formation. Ok. Think about where Greg Coleman is produced from and the communication between the hypothalamus and the church that will help you with your answer. Ok. We're gonna move on. The answer is the hypophyseal portal system. So his hypothalamus and his maturity gland. This part here is the anterior pituitary gland. And this bought his posture church grand the pituitary stalk connecting the two here. And this is the hypophysial portal system. So the hypothalamus communicates with the anterior pituitary gland via this hypophysial portal system. That was the answer to the S pa the hypothalamus secretes hormones into these capillaries, bring them to the anterior pituitary gland as an example of signaling. And then the anterior pituitary gland in secret its own hormones. Hypothalamus communicates with the posture of pituitary gland by nerve. These ones here in the pituitary stalk, hypothalamus stimulates posterior gland to secrete hormones. Are these hormones in the posterior pituitary glands are only stored there. They're actually made in hypothalamus. So the posterior posterior pituitary gland only to them, we've got different hormones produced by the anterior hormones. Pneumonic, we can use this flat P. So the flat part of the pneumonic, they're the tropic hormones. So they travel to other endocrine grounds to stimulate them, such as FSH LH, adrenocorticotropic hormone and viral stimulating hormone and then direct hormones. They stimulate the direct target directly such as pros and growth hormone growth hormone was the one in the FDA producing the anterior pituitary gland. Therefore, it's going to communicate via the that hypophysial system. The remaining hormones are oxytocin and ADH and they're produced, they're secreted in the posterior pituitary gland. Ok. We'll cover the glands. A patient has been diagnosed with an autoimmune condition aside from the symptoms of hyperthyroidism. They also have bulging of the eyeballs and a waxy appearance of the, of the anterior leg. What do you predict the patients thyroid function test will be, is it a low TSH, low, T three T four I TSH, low T three T four, I TSH it three T four, low TSH, high T three T four or normal TSH, normal T three T four. This is quite a difficult question. If you know what condition they have that can help you. If not, we'll get through it in a second. Hang out in the pool. The answer is d we'll go through what it is in a second. So here's the hypothalamic pituitary. A first. The para, when you hypothalamus released trh, just thyrotropin releasing hormones. GH then stimulates the anterior pituitary gland TSH, which is viral, stimulating hormone TSH, then stimulates the thyroid gland to T four and T three thyroid hormone T 24 and then bind to thy receptors, which is a type of receptor found the nucleus cells which lead to the transcription of metabolic rate genes. This thyroid hormone then inhibits trh and TSH in a negative feedback loop. What does T three and T four do? Well, it does normal bone growth and maturation, normal muscular function and development, normal nerve development, normal cardic output, normal hydration of the skin fertility and secretions in the gi tract. And it increases basal metabolic rate throughout the body. We can relate these functions to hypothyroidism that causes fatigue, cold intolerance, weight gain hair loss among many others. And also constipation. If you have a lack of thyroid hormone, you're gonna get a decrease in il and secretions in the entire tract. And that's constipation, hyperthyroidism. You're gonna get fatigue again, heat intolerance, weight loss due to increased metabolic rate, tachycardia, sweating among others. We're going to skip over hypothyroidism for now. But you can look back on in hyperthyroidism. You get two types, get primary hyperthyroidism and these thyroid function test results are gonna be a low TSH and a high T three T four. With hyperthyroidism, you'll have an increased amount of thyroid hormone. You have an increased amount of T three and T four in primary hypothyroidism. This excess of thyroid hormone is being produced independent of TSH, which then have a negative feedback effect on TSH. So this increase in thyroid hormone is will lead to decreased TSH. Example are examples of this is Graves disease, which is the topic of the FDA. We'll come on to Graves disease in a second, toxic and toxic. A secondary, a little different. You're still gonna have that high T three and T four called it the hyperthyroid condition. We're also gonna have a high th this is because there's an excess of TT three and T four which is being produced in response to increased TSH. The causes of this include a TSH, secreting pituitary adenoma and HCG secreting tumor is because HCG is quite similar to TSH. So it's going to act upon the thyroid to increase this thyroid hormone. And there's some treatment here, primarily, it's carbimazole that he used to treat hyperthyroidism. There are many other types of treatments. A thyroidectomy for you. It's only patient with hypothyroidism because they don't have a thyroid anymore. But it is much easier to manage than hypothyroidism. Ok. It's a graves disease. This is the most common cause of hyperthyroidism. The topic of the FDA, it's type of primary hyperthyroidism. But the problem is within thyroid. It's an autoimmune condition. The immune response is producing TSH receptor antibodies which mimic TSH is combined in the TH glands to produce access T three and T four is a picture of B lymphocytes producing these antibodies which can bind to the T eight receptors and then consequently increase T three and T four. This T three and T four being produced will negatively feed back on the TSH. So we'll get a low TSH. But these antibodies still being produced to further increase the thyroid hormone. And here are the symptoms. We have bulging eyeballs, the large thyroid glands and a waxy demin appearance of the anterior legs called pretibial my adrenal glands. The patient presents with central obesity, confusion and elevated cortisol levels. After further investigation, they are diagnosed with Cushing's syndrome. Pituitary adenoma is leading to the elevated cortisol levels. Your hormone is the genus creeping, releasing hormone, go to go releasing hormones, thyroid, stimulating hormone or aldosterone. To think about the hypothalamic pituitary adrenal la what was produced in the pituitary gland? Ok. I'm gonna end up all there. The answer is a, so most people out, right? Most people out, right. Adrenotrophin releasing hormones. Ok. Let's look at that Adrian there is on the top of the kidneys, we have an outer cortex and, and this is a cross section of the cortex We're looking at here, the er glomerulosa most superficial, the zonulata and the most deep is the zonal reticularis. So these are different layers of the adrenal cortex. They are once again the cortex and the mela two different parts, we have the glomerulosa fata andreis that we just talked about and the medulla and that's important in the secretion of catecholamines which are adrenaline and noradrenaline. Let's look at his office. So, hypothalamus produces C Rh, which is called releasing hormones. Crh then stimulates the anti to create ac which is adrenotrophin hormone. So that was the answer to the FDA. This pru adenoma is a PH which results in elevated cortisol levels ACTH out from the adrenal cortex act on the zona er that cause corticoid excretion like aldosterone. Yeah, the fat to cause glucocorticoid excretion like cortisol and it acts on the zona reticularity to cause androgen secretion like D hea and this cool. So has a negative feedback effect on both trh and A DT to to decrease its own to inhibit its own secretion als. This increases sodium reabsorption, potassium excretion and water retention to increase BP, cortisol. This controls the circadian rhythm, increases gluconeogenesis protein and lipolysis and influences mood and memory maintains BP by increasing the sensitivity of peripheral blood vessels and no adrenaline and adrenaline. It dampens inflammation and immune response androgens. They have androgens produced in the adrenal. Cor have a minimum role in adult men, mostly produced in the testes, but it does have a role in adult women and prebirth. Both sectors. It's also it's involving reproductive development, starting puberty and libido control reproductive hormones. We're gonna wh through this because we're running a bit over time. A man and a woman potential clinic, they have been having difficulty conceiving and the woman has a history of prolonged irregular menstrual cycle. The woman has a midluteal serum progesterone test as well as serum FSH. And I, what does follicle stimulating hormone act upon in female? Is it a to CB gran cell CCD cell or? Ok, I'm in the pole there. The answer was granulosis though we quick look at this, have a mature follicle with these granulose cells around about here and then just superficial. That was the T cells surrounding the mature follicle. Hypothalamus is producing DNR H which is gonadotropin releasing hormone. GNRH is then stimulating the anterior maturity glands. Remember the flat PGP, mnemonic discrete LH and FSH. LH stimulates the cells of the follicles in the ovaries to cause androgen production. And gene Rh and FS H stimulates the granulosa cells of the follicles in the ovaries. That's the answer to the BA FS H acts on these granulosis cells called inhibin production and estrogen production. FS H is responsible for follicle development and LH is responsible for population. OK. Uh I'm not gonna go over a different part of the menstrual cycle. Now, a whole another topic in itself, but here's a quick summary of it that you can use for your own revision once you get the flight and here we have brief summaries of the axis of the, of the axis in male, quick summary, anterior pituitary hormones. We can remember them using flat PG and the posterior pituitary hormones. The ADH and Oxytocin, the most common cause of hyperthyroidism is graves disease and it's treated with carbimazol adrenal cortex, aldosterone cortisol and androgen in male LDH act on LH A and you can look back at the previous slides to find out why and in females, LH act from the cells. FSH acts from the granulosa cells and the follicles in the ovaries. Great. That's all all for me. Thank you very much. Wow, that was a great joke. Um So I think I'm doing the next one. should give you guys a minute just to take that all in. That was really, really well taught. Jo Thanks so much. That was great. I love you so much. Um I just wonder if you mind doing the polls as well, which I present, but I'll just give everyone a few, like a few more seconds just to get their head ready. We're nearly there. They nearly at the end six. Are you guys able to see my screen? Yeah, we go. Ok. I think I'll just get on with it now so we can finish on time. So I'm gonna be talking about the gi nervous system and pharmacology. Um, these aren't my slides, unfortunately, that A's, um, she wasn't able to make it today. Um, so I'll try my best to, to get it right. But, um, if I don't know anything, I'm sorry, in advance. Ok. So, um, a 23 year old patient with cystic fibro fibrosis has noticed that they're experiencing cramping gas and gas and loose greasy stools after visiting the GP, they found out these symptoms are commonly experienced by individuals with cystic fibrosis due to an overproduction of mucus causing a blockage in the pancreas. A lack of which enzyme in their digestive tract are most likely the cause of their enzymes of their symptoms. Sorry. Oops, I now. So I'll give you guys a little bit of time to I think and see what you think. Really nice. Just have a go even if you don't know the answer. Yeah, a few more seconds to see if you can have a little bit more think. Ok, I think we'll end the pole. So, yeah. This one's a really tricky question. Um When I was going through the slides, I can get it right myself. Um So the correct answer on this one is Amylase. Um So I'll talk about it a little bit more in a second, but one of the kind of key clues in this question is that it's um blocking um the pancreas. Um So we're looking for, we're only looking for enzymes that come from the pancreas. So immediately we can get rid of um Pepsin maltase and trypsin because none of them are produced by the pancreas. Um So we're going on a little bit more about the digestive enzymes. So this kind of is an overview of all of the different enzymes um which you can see so that we've broken down into the ones that break down carbohydrates, proteins, fats and nucleic acids. So it's really important with these ones is to kind of know where they're produced and also where they're released. Um I think it's really good if you can um learn the kind of function, the specific function, but if you don't have the time, don't stress too much about it. But yeah, so this one was talking about amylase, amylase um As you can see, is released from the pancreas and it is acts in the small intestine and its role, its role is to kind of cleave um gliotic gliotic bonds to break down that kind of carbohydrate structure. So that's kind of what's causing these symptoms is a lack is a break, is a lack of breakdown of carbohydrates. And as I said earlier, the kind of clue in the question was about where um in the body, sorry, where the uh hormone is being produced, sorry, enzyme is being produced. So as you can see that pancreatic amylase comes from the pancreas, whereas the other ones are coming from the brush border. So the brush border is kind of the inside lining of your small intestines. Ok. So you guys will get these slides so you can have a proper read of these a bit later on. But I think we'll just for the sake of time, keep moving. So the next question is a 45 year old man has begun experiencing symptoms of nausea, vomiting, acid reflux and rapid weight loss. Imaging and blood tests were conducted which revealed a pancreatic tumor and high levels of gastrin in the blood. As a result. He has developed az he has developed Zollinger Ellison syndrome. So which of the following is gastrins function? So I'll lower the pole now for you guys and just see what you guys think. I lots of answers coming in. She was good. Has a little bit more time. We call end the pole there. So yeah, really, really well done guys. Pretty much everyone got the correct answer for this one which is c so a little bit about what's Ellison syndrome is, is when you have, um, this kind of, as you've got here, pancreatic tumor and it's secreting lots of gastro into the blood. And so this gastrin, um, then stimulates as the correct answer is the secretion of gastric acid and this secretion of gastric acid then needs to kind of peptic ulcers. So there's like ulcers in your duodenum on your stomach. Um, there's kind of three main causes really of, um, of ulcers, but that's not something you need to know at the moment. That's just a little bit of fun fact, which we'll learn a bit more later on in case six. So, yeah, going on to the roles of the different hormones. Um So as you can see here, we've got gastrin, um which is um stimulates secretion of gastric acid and intrinsic factor from parietal cells. Um And what we've done here is we've kind of got the list of the hormones on the side and then their kind of main function is the one highlighted in red and also where they're, where they are released. Um I think it's really important. The top five ones I say the most important, the gastrin, the CK secretin motilin and somatostatin. So, II don't think I'll go through these ones again just in the interest of time and you will all get the slides at the end as well and we'll give you the feedback form. But yeah, so gastrin stimulates the of gastric acid and intrinsic factor from parietal cells. Intrinsic factor is really helpful for um or is very useful in the absorption of B12. Um And so that's a key part of the absorption of B12. And you've got CCK which simulates called bladder contraction, release of pancreatic enzymes and releases the sphincter body, which is kind of where the uh common bile duct or sorry, the um Artal duct or whatever it's called. I can't remember the name of the phrase um joins the small intestine and that's how the kind of pancreatic enzymes and a bile all join together into the small intestine. Then you've got secretin which stimulates secretion of H of bicarbonate from the pancreas. Um VIP increases water and electrolyte secretion of pancreas and the guts. G IP reduces astro secretion. Motilin increases small b small bowel motility. Um and somatostatin inhibits secretion and action for many hormones, including all of the above s So next question for you guys. Um a six year old, a 60 year old woman has hypertension. Sorry, my thing is in the Thank you. A six year old woman has hypertension. Hypertension was given a surprise birthday party. However, during the course of the party, she began showing signs of slurred speech and facial drooping and balance issues given a possible diagnosis. What condition does she have? This one's quite a tricky one. So don't worry if you guys can't get it, just really want to pull for you now. So, is it a upper motor neurone injury, b lower motor neurine injury, C Brown SARD syndrome, D myocyte gravis or E Bell's palsy. So yeah, I really nice to get to see the answer coming in. Uh a little bit more time has another 15 seconds. See if he can have a guess. So, I'm gonna end the pole that. So, yeah, this one was a really, really tricky answer. So the correct answer is upper motor neuron injury. So based on the presentation, it seems as though um she's had a, this woman has suffered a stroke, um you know, kind of CLS towards that is how quickly it came on. And also the fact that she's got hypertension. So I think the second, the one of the other popular answers was a Bell's palsy. So these do have very similar presentations to stroke. So I can see why you guys have gone for that as well. And there are kind of subtle differences in, in Bell's palsy and stroke. So in stroke, you get preservation of your um being able to raise your eyebrows. And so it's called forehead sparing. But in Bell's palsy, you don't. Um but kind of given how rapidly onset this was in the patient's risk factors, it's more likely to be a stroke which is a type of a urine injury. So going on to explain upper motor neuron injury versus slow motor neuron injuries a little bit more. So upper motor neuron injuries present in the in the descending into neurons of the corticospinal tract. So what this is is that is the um is the tracks which are coming down from the top of the brain. Oops, sorry, oops, sorry, which is coming down from the top of the brain and then traveling through the spinal cord. And then it's as they leave the spinal cord that they then become lower motor neurons. So between the brain and through the spinal cord, they're upper motor neurons as they leave the spinal cord, they become lower motion neurons. So the cell bodies of upper motor neurons are found in the primary motor cortex which is in the brain. So some causes of uppermost neurine injury is stroke, multiple sclerosis, traumatic brain injury, atypical parkinsonism, cerebral palsy and an amyotrophic lateral sclerosis, which is the most common type of motor neurons disease. On the other hand, lower motor neurons is when you get injuries to neurons which innervate um muscles directly. So that's when they've got their cell bodies which line the ventral horn of the spinal cord. So it's as they're leaving the spinal cord, they become lower motor neurons. So some causes of this would be um trauma to peripheral nerves, viruses, guillain-barre syndrome, botulism, corr syndrome, and again, amyotrophic lateral sclerosis, which is again, motor neurons disease that has both upper motor neuron and lower motor neuron um injuries in that disease. And also like we said earlier, Bell's palsy. So, in terms of how to recognize an upper motion neurine versus a lower motion neuron injury. So, one of the big things is paralysis. So upper motor neurone tell mo lower motion neurons to both relax and contract. If you lose the upper motor neuron, then you can't tell your muscles to relax anymore. So, what you get in upper motor neurons is you get spastic paralysis, which is kind of when your muscles are all rigid and locked in place and you get tonic spasms as well. With that, on the other hand, in lower motor neurons, the muscle tone is completely lost. So you'd have kind of floppy paralysis. You wouldn't be able to move and everything wouldn't be none of the muscles would be tensed and things like that. So in terms of muscle bulk, so in upper motion urines, it's normal. Whereas in low motion urines, it's atrophied, so it's wasting away, then you also get your deep tendon reflexes. So in upper motion urines, they become hyperreflexive. Um So it's an over exaggerated response. Whereas in later low motion urines, they're either hyperreflexive, so very dull response or they're absent. And in terms, a babinski sign, um which is when you kind of stroke the bottom of the foot. Um this normally will cause the toes to go down apart from in babies where it causes them to go up. So, Babinski sign, if you have a positive Babinski sign, it's when your toes go up. Whereas and that's positive in upper motion neurons, but not in low mo neurons, then you have muscle fasciculations, which is kind of uncoordinated, involuntary twitches. So these are present in low motion urines, but they're not present in upper motor urines. And finally, you have the clasp knife reflex, which is um upper motor neurons present in occ mo urines. And if you imagine kind of when you're closing a pen knife, it will close very slowly, then suddenly jerk. So that's what you can kind of get with the reflexes in occam urines as well. So a really good way that I like to try and remember the difference between upper motor neurons and lower motion urines is upper motion urines, everything goes up. So your tone goes up, your height, your reflexes go up your muscle bulk, well, that one stays the same, but um your buns time your toe points up. So in upper motion urines, everything goes up. Whereas in lower motion urines, everything goes down. So if you guys have any questions on that, please feel free to mention them in the chat. Um But yeah, just going quickly back to this question. So, um the reason it's not brown s syndrome is that is an example of a low emotion or an injury and that's when you get damage to the spinal cord. Um or it's, it's not, it's a upper and lower injury, sorry. Um And that's gonna present differently to how this is presented. So in Brown syndrome, you get half of the body on the same side as the injury, you're gonna get loss of your um motor and two point discrimination. So, vibrations and then on the contralateral side to the other side, you're going to loss of pain, temperature test and things like that. Myia gravis is an autoimmune condition and this causes kind of um particularly problems with the eyes. So you kind of get um paralysis of the eyes, you get pain in the eyes. And one of the key things about mycin gravis is that the more activity you do the worse it create, it makes the um the paralysis. So going back forwards again. So we've got another question for you guys. So a little girl was helping her father in the kitchen when she unknowingly touched the hot pan, she quickly pulled her hand away to to experiencing excruciating pain, which of the following nerve fibers was responsible for her feeling the sharp pain. So just get the pole for you guys. So is it a alpha fibers, a beta fibers, a delta fibers, c fibers or D fibers is coming in another 15 seconds. So, and the pole. So my mouse doesn't seem to be working. Sorry guys, is someone else able to end the pole for me? Sorry, I get back. OK. Sorry. So the correct answer to this one is a delta fibers. So we'll go on to talk about what the different fibers do now. So a alpha fibers are um the fibers which are responsible for proprioception of skeletal muscles. So that's kind of our knowledge of where our muscle is in space. So they're myelinated. So because they're myelinated, it means they're really fast. So they've got a conduction speed of like 80 to 20 milli uh nanometers per second. And for example, of what they do is um reflexes. So they're responsible for your reflexes. This next lowest um uh fiber is the A beta fibers. So these are innovating things that were unresponsible from the camera receptors of the skin. So again, they're myelinated. So they've got a really fast conduction speed of 35 to 90 m per second. Um And there's 6 to 12 nanometers. So you can see they're kind of all getting smaller in size as we go down. And examples of what A B to five is gonna respond to is tactual pressure. Then you've got a delta fibers which are pain. Um So that's mechanical and only thermal. Um and then also temperature as well. So what they do is they're also mated again, they're getting smaller and they've got a slightly slower conduction speed. So they're responsible for that first sharp localized pain. So kind of, you know, if you kind of stab yourself um or something like that, then that initial pain that you feel, that's what the A delta fibers are gonna be responsible for on the other hand, you've got your sea fibers. So these are responsible for pain. They do mechanical thermal and chemical pain as well, um, as well as temperature and itch. Um So they're not myelinated. So they're much lower than the others and they're also much smaller. So they're naught 0.2 to 1.59 and they're naught 0.5 to two millimeters per 2nd, 2nd induction speed. So they're responsible for that kind of second, slow nonacute nonlocal pain. Like I was saying earlier, if you got stabbed, you have that initial sharp pain, which would be from your A delta fibers, then afterwards you kind of that dull aching pain, which would be from your C fibers. So going on again, got another question for you guys. So a 65 year old man who has been diagnosed with chronic myeloid leukemia, it's a cancer of the blood driven by an overproduction of protein kinase which proliferates cell survival. What kind of novel anticancer drug would be an appropriate treatment? This one's a very tricky one. When I was reading through these slides, I was not able to get the right answer. And so don't worry if you guys aren't sure I not the p pretty good to see those ones come in guys. You guys like another 20 seconds. I think we'll end up on that. So, yeah, so most of you got the right actually, really well done. So the correct answer is is it's a tyrosine kinase inhibitor C this is just kind of showing a diagram of kind of the regulation of cell proliferation, um growth and also angiogenesis. So this shows how it works. So, initially growth factor binds to tyrosine kinase receptors which is a transmembrane receptor on the cells. This then um triggers um phospho phosphoinositide three kinase, the I three K um to be phosphorylated which begins the P IP three cascade. So P IP three phosphorylate a AKT, which is also known as protein kinase B um which then goes on to P phosphorylate MT or or mammalian target of rampy MT or as you can see here then activates transcription factors like SK 61 and four EB to promote cell survival and proliferation and angiogenesis. Just a note, I would be very, it's very likely that you need to know the examples of the transcription factors. Um that's just a little bit of extra detail just to try and help with your understanding of it. So, because of this path that it gives us three kind of um enzymes interactions that we can kind of inhibit to try and stop this um proliferation. So the first one is the one in the question, which is a tyrosine kinase inhibitor. So if we inhibit our tyrosine kinase um receptors, um then we can inhibit the um the the signal ever starting. So the signal never begins. So now this um cascade is gonna happen similarly, if we inhibit the pi three kinase inhibitors or pi three kinase. And again, we're not gonna get this cascade leading to this conscription factors leading to this proliferation. And then finally, we have our MT or inhibitors which has a name suggest H the MT. So essentially, each of these inhibitors are stopping this cascade happening. If we stop, stop this cascade happening, then we stop these transcription factors being um being created, you will come on a bit more to kind of anticancer drugs in um absolutely cycle in case 16 as well. So in the second year, so we don't worry too much at the moment if it's something that you're struggling with, it's definitely something I struggle with. So going on again, we've got another question. So a lot after a large meal, a 70 year old woman experienced a burning, painful sensation in her chest, initially panicked thinking she was having a heart attack. She was rushed to A&E after a history was taken, it was determined she was experiencing acid reflux as opposed to as opposed to an M I. The doctor finished the consultation and prescribed some medication to take home, which the following type of medication was the woman prescribed. So again, I'll get the polls. Sorry, I've just shown you how them um I'll still run the polls just in case people miss them. So which yeah, as I guess most pretty much I got to get, I'll give you guys like another 10 seconds. We'll end the pole there. Um So pretty much everyone got the right answer. Which is the so sorry e it's a proton pump inhibitor. So some of the other um we prescribe a protein pump inhibitor. I'll talk about it a little bit more, but that's what we often prescribe for acid reflux. Aspirin is a type of NSAID. So it's to do with clotting and painkillers. Uh And yeah, and then morphine is auto a painkiller. Paracetamol is auto a painkiller. And then beta blockers are things we used to kind of treat the heart when it's working too hard. So a little bit about gastric digestion regulation. So as you can see from this diagram, we get um hydrogen sorry, water and carbon dioxide which um move into the cell by themselves are then combined by something called carbonic anhydrase. Um This is then broken down into bicarbonate and hydrogen. So our hyd hydroxyl irons um combined with CO2 to form bicarbonate. And this is catalyzed bicarbonate anhydrase. So that's just the explanation of that bit, sorry. So then bicarbonate ions are then transported out of the parietal cell into the blood. Um And in exchange, we get chlorine entering the cell. This is to try and maintain this kind of intracellular ph, but we're also gonna have the chlorine be moved across later as well. So this bicarbonate in the blood causes an alkaline tide which causes a slight elevation of blood ph. However, this is kind of offset by in the pancreas, we have the reverse being happening, but we get hydrogen pumped into the blood. Um and bicarbonate being pumped out into the kind of gastric sorry pancreatic um juices. And so um bicarbonate is pumped out and uh the hydras however, are pumped out of the cell into the gastric pits. Um and potassium are pumped into the cell by the proton pump. So you can see this happening here by the use of ATP chlorine ions are also, as I was saying earlier, pumped from um into the gastric pit out of the cell. And together they're gonna combine with um hydrogen to form hydrochloric acid. So how a proton pump inhibitor works, which is what we talked about earlier. Is it inhibits this potassium? So hydrogen potassium at ps which is known as a a protein pump. So if hydrogen isn't being pumped out, then there's no hydrogen in the gastric pit for the tot with. And so um hydrochloric acid isn't gonna be made. So then going on, this is the last question, guys nearly at the end. So I'll just not the pole a second. So an eight year old boy, um I'll let you guys read it and see what you guys come, what you guys come up with. So yeah, so an eight year old boy has fallen off the monkey bars in a playground inches, ankle has become red and swollen and the boy won't stop crying, he cannot walk on it. And the parents decide to take him to the GP. The following morning, the GP examines his ankle and range of motion and decides that it was just a sprained ankle, which of the following medications is the GP most likely to prescribe for the pain. So, yeah, I really good coming in, you have another 10 seconds. Just have a guess if you're not sure. OK. And what end up? Pull that. So the correct answer is paracetamol and we'll go on to that in a little second. Um So the World Health Organization has this thing called analgesic ladder, which is basically an order in which we give our um in the order in which we give our drugs. So the first step on the um analgesic bladder is non opioids. So these are things like um nsaids. So that's examples like Ibuprofen aspirin, what might be paracetamol? This is kind of when we're having only mild pain. So severity 2 to 5 out of 10. Um if opioids, sorry, non opioids weren't proving effective or if it was a much higher s of pain, then move on to our second step on the ladder, which is mild opioids. So these are things like Cocodamol, codeine and dihydrocodeine. And so Cocodamol is just um paracetamol and codeine in one. So it's also important that if you prescribe a patient, Cocodamol, that you ensure that actually you tell them don't take any paracetamol as well because otherwise they might risk having a paracetamol overdose. So, again, this is for moderate pain severity about 5 to 8 out of 10, or if the non opioid options haven't worked. And then our last option after we've got through these, in terms of analgesia we can give is our strong opioids. So this is our morphine, diamorphine and fentaNYL. This is for severe pain or when you've kind of got severity. So severity eight plus out of 10, um you really don't want to be, you want to always start on the lowest um level that you can and whatever seems appropriate because you can always move up, but it's quite hard to move back down. So really try and save your steroid periods for the very last resort. Um And just importantly, to mention about aspirin, um in terms of that question, the reason why it wasn't the correct answer and proceed was preferred is because um you wouldn't give aspirin to someone under the age of 16 because there's an increased risk of something called Reye syndrome, which is essentially you kind of get dysfunction of the liver and then it also causes swelling of the brain. So yeah, just for some reason in the World Health Organization ladder, start with your non opioids like nsaids and paracetamol, then move on to your mild opioids. So Cocodamol, codeine dihydrocodeine, and then finally, your last option is your strong opioids like morphine, diamorphine fentaNYL. And at this point, you might also consider sedation if you're not able to get on top of the pain. So that is the end of that slideshow. So I'm gonna stop sharing my screen now for a second. I'll just paste the feedback form into the chat as well if you guys just give me a second. Um But yeah, if you guys have any questions, we're happy to stick around a little bit and answer any that you might have. But apart from that, thank you. So, so much for coming. I know that it's late on a Sunday evening. Um, there will be more teaching sessions from, um, so we've got the P CS part three tomorrow and Tuesday and then we're also doing another kind of crash course of SBA S um, before your F two. But what I can say is best of luck for your, um F one. It really doesn't mean anything. Don't stress too much about it. It's just a practice paper associated in that way.