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It's legal, but don't worry about that. Um I put my email there, if anyone wants to get in touch with me, I'm happy to help with anything through the fifth year. I also have a mentee. So if you just go on into your contact in the code, um that will just help along the way fine. Um So I'll just get started with some general kind of path advice. I think you guys are getting near towards the point where you actually want to be. Um We're nearing the point where you might actually have to start working. Um So I just thought I'd covered bit about path generally. Um I remember it was very intimidating to me. You kind of start for a baseline of, of knowing nothing of being very confused by the whole thing. Um And it does feel like a slog especially. So we had it like every Wednesday for the whole year, you guys have it in these blocks now. Um But looking back, it really does help you for finals. I think they do it in 50. It just so you don't forget all of medicine. Um And it does make you a lot more confident, feel a lot more confident, rather feel a lot more capable. I teach you a lot of medicine is probably the best like module in the whole of the six years. To be honest. Um I think for people I've spoken to in your year group, you guys appear quite so anxious about path. I think the way they've done it this year probably hasn't lent itself very well to feeling confident. Um But my piece advisers just don't worry about it. It's not actually that bad. They write the course they write the exam. And if I'm being honest, I think they put a minimum number of questions in that either easy or repeat that you basically don't fail at. Um So don't worry about that if you want to do. Well, also, don't worry, I know it seems endless and there's so many lectures but honestly, like, well, I'll cover that in a bit, but the important things to cover is a costly content. Um not to be all and end all but very important social history. That's Rob Golden. Um And he also gives very good lectures that generally genuinely like quite useful. Um in terms of resources, this isn't just to do just the past, this is to like do well get the Viagra if you want that. This is everything I used really the path guides, really all you need to know if you ask me. Um Yes, there are books there's a mirror book, actually I forgot to put on here, which is okay. It's a bit outdated, but honestly, like the path guide as everything you need to know. Like it's, it's a really impressive thing that they put together. Um, it's really helpful you can get go really overboard, get all these books, um and all this other stuff, but it's just not necessary to be honest if you ask me, medicine is good for VSA prep. Even though the questions aren't that representative and past paper, questions are really useful. Um That being said, there's no right way to do it. So whatever works for you absolutely fine. Um But just don't go overboard. That's what I'd say. Um Last thing is like looking back, like, don't get to enjoy yourselves a bit. You don't have much time left. Um You won't remember the extra day you spent doing path when you're done when you're a doctor, when you're striking, whatever you will remember, like if you went out with your friends or if you wanted something fun. So don't forget about the purpose of these things. Fine. So this talk going to cover all this with high yield areas of history, I think, which you haven't really come across in year three. What I say is the histopathology is kind of just like medicine um in year three all over again. Um I think you understand as I go through it, but there's some areas of it that do tend to come up and feel very specific, but it just cause you don't cover them really in the past. Um I'll try and focus on understanding fundamentals. I won't go through kind of the nitty gritty details that you can really get into because you can just learn that it's not difficult to understand. You can just sort of mash it out and learn it. Um And some things you just need to do that in path. I'm more focused around kind of getting to understand the basic principles because that's really the key to understanding tricky topics. I think you can just learn a table, but it's harder to learn if you don't get it if that makes sense. Um Hopefully you'll feel a bit better about path in general after this. So I won't do is go everything you don't history, you can't do that in one or even two like lectures. Unfortunately. Um provide you with a bit of information, need to get distinction, same sort of thing. You can't cover everything and I won't cover the minutiae either. It's mainly just the fundamentals and the principles as, as I said. So this is just an outline of the content, not in that order. Um um I'll start, I'll front load the tricky, conceptually difficult things, the nitty gritty. Um And we'll do that if you just go onto the mentee. Um I actually do have a little thing just to gauge how everyone's still feeling about path. Um So I don't know if it's active, but if you could just fill that in just so I know where to pitch this and kind of how, how deep to go, I guess. Um, it should be working but let me look fine. So let me have a look at it fine. So pretty bad. I think it's on 2.9 right now. Um Fine. So we'll go over the basics, we build up. Um Yeah, don't worry too much fine. It all comes together when you advise. I promise you find. So Renal, I think we'll start off with renal, I think is one of the trickiest topics in medicine to understand we'll go through that start from the basics. Um A kind of us to CKD. So normally I think someone's off, that's fine. Um So one thing I would say is if you have any questions, well, I, I guess we'll leave until the end and that's fine. Uh but just put them in the chat and I'll cover them at the end as you go. So, AKI um uh basically the way to think about it is it's, they're both so achy and see, could you both when the kidneys stop functioning? Right? AKI is just an acute decline in renal function. Very, very simply leading to a full in urine output. The kidney is many different functions. But the primary one you want to think about from this perspective is urine, output, water goes through or your blood goes through rather gets filtered, uses urine. It's a sort of input output type situation. Um It's captured or measured or you kind of know you have an A K I based upon the creatinine levels and the urea, as seen on the user knees, there is a criteria for this. I don't think you need to have a path. The main, the main concept you get your head around is acute versus chronic. Okay. And the way you measure them. So that's why you do a U N D whenever anyone says I would do kidney functions test for using these. This is what they made me mean, creatinine and urea chronic kidney disease is basically the same thing and the theology of these things kind of linked even. Um So that's why it can be a bit confusing but over a longer period of time, generally due to progressive damage and it's staged by the E G F R or the estimated glomerular glomerular filtration rate, which I think is related to creatinine and stuff like that but not directly sort of, it's not the same if that makes sense. So both of the result of the pathologies which we'll discuss, which is what imperial really wants to know and focuses on. So CKD um or chronic kidney disease is kidney damage or decreased function as shown by the reduction in E G F R present for over three months. So it's that sort of timescale thing is chronic rather than acute. So decrease in kidney function. Um It's measured like this and you have this grading scale, this I would learn. It's quite simple. It goes in batches of 30 until it goes in batches of 15. So I just start from the bottom mark. Just remember less than 50 in the end stage. That's when you need dialysis and you build it up 15, 30 30 45 45 60 62 19. So first one is the big drop. Um And one extra notices that in stage one and stage two, um if you don't have symptoms, you drive CKD and the primaries or symptoms CKD, which you'll get at this stage is protein area. So a positive protein dipstick, we'll talk about that later. Um Don't ask me why they split up. Stage three and 33 be, no one knows. I think even like actual like F one F two registrars don't know. So that's a renal thing. I wouldn't worry about it. So it causes two. Most common causes diabetes and hypertension. There are a few other ones would be good to have an idea about. So that's autosomal dominant polycystic kidney disease. That's A D P K D. And another thing is that any AKI in theory can sort of cause CKD if you don't treat it because obviously have acute damage, the kidney. One of those key distinctions between A K I C K D is that A is reversible CKD is not. Um whereas, and so if you don't treat the AKI you get damaged, get necrosis. Necrosis leads to fibrosis leads to a lack of function which leads to chronic kidney disease, which is progressive and you can't, well, yes, progressive. You can't treat it really. So things like pilot nephritis, if that's bad, you can get CKD if you have a 2 80 N or cute tubular necrosis, which we'll talk about again, similar concept and obstruction as well. So I think most of the pathologies that they want you to know about more cover the AKI side of things. We'll talk about that. Now, the best way to deal with this is to think anatomically. So what I would say is think about it as you know, from third year, pre renal renal, post renal. So prerenal very simply decrease in blood flow to the kidneys, hypervolemia, all your types of shock, essentially. So you have um cardio cardiogenic neurogenic uh sepsis. Uh Any other ones you can think of hyperbole, make very simple. Um and also things like reality stenosis, but basically not enough input means you can't get out put, you can't get your own production. That's the way I think about it. Um Another ways you can think about in terms of reduced profusion. So the kidneys aren't getting enough blood tissue doesn't get enough blood tissue dies. Therefore, you know, lack of function renal, this is more they want you to know about to be honest, the more most complex bit very difficult to understand. Sometimes if it's not explained properly, I think direct damage to nephrons, the real functional units of the kidneys, okay. Post renal surgical cause is basically a blockade to out blockage of outflow. So a stone or something in the tube blocks the flow. I mean you get back flow into the kidney backflow means that the pressure gradients messed up, you can't filter. And so the kidney starts to go kaput very simply as well. It's the most common cause of AKI prerenal. The second most common is post renal. What they want you to know about is renal. So we will talk about renal, the post prerenal, post renal, that's more like medicine, renal is more of the path. So we'll talk about renal. So intrinsic renal pathology again, think about the anatomy. That's how I do it. If you just try and learn every individual pathology, you will just get overwhelmed. It just doesn't make sense. So just think about it by anatomy. So you have the gonorrhea list itself, which is this blood vessel bit here. Um I don't know if you can see my cursor, but that's what it is. You have your nephrotic and your nephritic syndromes. So we'll talk about the difference between those. But you have a sort of category or group of diseases which fall under the thing of nephrotic syndrome. So if you remember a syndrome is just a name for a set of symptoms, that means like a bundle of diseases which have that set of symptoms. So, um for example, why I wouldn't say that's more confusing, but it's a bundle of symptoms and under that bundle, a bundle of conditions for um um Nephritic syndromes, similar things, you have a bunch of different causes. That is to say that basically nephrotic syndrome is not a disease in and of itself, it's a description, basically blood vessels. Um That's basically the blood vessels supplying the glomerulus. You can have things like H US or human Your Remix Syndrome. TTP um which you remember third year again and the tubules which are the other bits sort of around here, acute tumor necrosis, acute incision arthritis, very easy to get them confused. We'll talk about all of this in more detail now. So let's talk about the glomerulus first, the most difficult bit to understand in my mind. Um I think this was said in the previous sister talked about just re outline it for the actual exam. I'm like 95% sure. You do not need to look at slides like this. You don't need to look at pink slides and say like what is this? Identify it? I know you guys apparently have had some kind of mock where you had to do that. Maybe things have changed. But regardless, I don't think it's worth your time to learn it. I don't think they'll give you a, to learn and be able to distinguish these things in a meaningful way. Would take you so much time that it's not worth the extra marks. Everyone will lose those marks. Don't worry about it. Um I'm only showing you this because I think it helps to conceptually understand what is going on and understand the structure. Um because you read, if you just learn it from a book, you read these words, you don't really understand what they mean. Like what's in mesangium? I don't know. And you just kind of learn it, but this will help you to actually understand it. So basically this bill pink bit blood vessels capillaries and then you have this bit in between, which is the mesangium, which basically connected tissue. You have the Bowman space, blood flows through the Bowman space through the potty sites, filter all your protein, all the big stuff. Well, big crack gets filtered out, stays in the blood, the water, the electrolytes they go through. That's the main concept I want you to get. So mesangium is basically extracellular matrix, basically connected tissue capillaries, blood vessels, blood flowing through them Bowman space. What things are filtered through and the potty sites, what actually does the filtering? Um And that's about it. And once you get an idea of what this actually looks like. Once you can picture in your head, you can start to understand why things go wrong. But don't worry about the specifics, just concepts. So, nephrotic syndrome done by a very specific triad. So peripheral Adema protein urea and low serum albumin, it really does make sense. So basically the filter breaks down, you piss out or your protein, you can't keep it in. So you have a, that means you have a low protein, mouth protein in your blood. And it also means because you have low protein, your blood, you start to get um fluid everywhere building up because you don't have the oncogenic pressure. So these all kind of linked together, you also have an increased cholesterol and clotting tendency. That's because U P out one of the proteins, which is antithrombin three, that sort ties into hematology as well. And you've increased cholesterol because you're losing so much protein, your liver just starts producing loads and loads of stuff. As part of that, it starts releasing more cholesterol. So simple concept, all nephrotic nephrotic syndrome conditions uh issues with the port sites. That's the filtration barrier, the potus sites break down your filter, breaks down those big things that are being stopped by the sieve they start to get through. So you lose protein. That's the simplistic way that when you think about it, that's the way it makes sense and treat all of them with steroids. The main thing to know is how they actually respond to steroids. So you have to be throwback, starting off minimal change disease. Why is it, why is it called minimal change disease? We'll talk about that. So it affects kids. That's the main thing. That's the main differentiator affects Children. It's called minimal change. You might remember because I'm like microscopy, you see nothing. It looks normal on electron microscopy. You see a loss of the foot processes of the pod sites. Potus IPOD Latin means foot, foot cell. Okay. So a lot of the names of these things make sense. And I kind of say if you can work things out from the first principals, you don't need to memorize it. Life becomes a lot easier. Um Pathologists, I shouldn't say they aren't imaginative, but they aren't that imaginative. They name things very simply based on what they look like. And it's some oftentimes does make sense, not all the time, but often times it does make sense. Um The main thing to know light microscopy, no change, electron, you lot lose those foot processes. You can see it's kind of breaking down immunofluorescence. So these three types of microscopy same for all of kidney. So light electron lights basically just taking a look through light microscope. When he didn't. First here, electron taking a really closer look, much more specialist, see all the detail immunofluorescence. That's when you're looking for immune complexes. So using a much more sophisticated technique, but basically, it's synonymous with immune complexes. That's how you should think about it and minimal change responds very well to steroids. I think it's like 90 90% of people recover with prednisoLONE moving on member anus. You might remember this is the one that affects adults. So adults moving to the histology. So this is immune complex mediated. So you see a diffuse basement membrane thickening. So you see it across the entire basement membrane. Remember that's that space with the Bowman space depositories attached to that, that's doing the filtering. So you see basically immune complexes attaching to the basement membrane, but they're doing it evenly across the whole thing. When you go a bit deeper, you see spiky immune complexes because immune complexes, I guess they're bitty, the spikey. That's how I think about it. And then on immune inflorescence, you see immune complexes across the entire basement membranes are uniformly across the whole thing. Okay. This responds much more poorly to steroids and it's associated with some antibodies. So anti phospholipase a two antibodies, something you just have to learn and sle. So I think they talked to you about etiology of sle within the course I can run through it later if it doesn't make sense, but essentially sle very much immune complex related. So that's how you can think about the association there. Next, focal segmental glomerulonephritis. So again, break down the name. So focal means only some glamorous light are damaged. So if you take a section of kidney, only some of the memory light within that section will be damaged. Not whereas diffuse means across the entire sort of section across the whole thing. Segmental means only some regions of each individual glamorous lists are damaged. So if you look here, you see a normal one. So you hear some of its damage, not all of it, it also tends to affect adults and you go on to the actual histology. So in light microscopy, you see focal and segmental scarring. So, sclerosis or so sometimes I should say F S E S focal segmental glomerulosclerosis is sometimes called or glomerular nephritis. But basically sclerosis means scarring means fibrosis means lack of function. So, focal and segmental scarring, electron microscopy. As you see with everything else, your loss of the foot processes and immunofluorescence, you see nothing because there's no immune complexes involved here. And this again responds less well to steroids. So in terms of steroids, best one is this minimal change member. This is the worst so far is very poorly and vocal segmental is sort of the middle ground. So less well but not the worst. And that's about the detail you need to know in there's some secondary causes which can of of um nephrotic syndrome. So these are less important. One is diabetes, which I guess makes sense diabetes. One of those big things that affects the kidneys and on histology. Buzzword, you need to learn it. Kimmel steal Wilson nodule. The second is amyloidosis. And for that, the buzz word is apple green, congo on the congo, red stains, apple green by refrigerants on congo red staining. That's quite pervasive cross paths. I would learn that. And two types of amyloidosis A L. So A L L for light chains, light chains, multiple myeloma. So you're getting all these plasma cells being malignant. The plasma cells produced loads of antibodies, the antibodies clog up the kidneys damage it. That's how you get the damage A is you to any chronic inflammatory process. So for example, sle rheumatoid arthritis, because a a amyloidosis which damages the kidneys. A basic concept to understand which I think I'll run through. In the next slide is basically big proteins, big immune complexes damage the kidneys. Um but we'll talk about that later. But this is secondary causes important to know but not as important as the first three things if that makes sense fine. So moving onto nephritic syndrome now, so the way to think about this is again a triad. So a triad of hypertension hematuria and adama. So quite different hematuria. Um do damage, peripheral edema. Um do you against part part of the filtering and hypertension? I'm not sure why, to be honest, but when the kidneys tend to get messed up the hype that you tend to get hypertension, probably due to the reimagine angiotensin system. So itis in anything means inflammation, which means damage. So you see red cell costs within the urine. That just means basically some big cells are getting through cause of kidney damage and you can see them within the microscope. So a cast basically just means a bit of cells been forced through the sieve. That's how I think about it. And you see damage to use the knees. And these are really your causes of AKI your glomerular nephritis. These um nephrotic syndrome causes a break in filter which let's protein through this really damages your actual kidney function like globally, this is the stuff that gives you acute kidney failure and stuff like that. But it should be said that these syndromes see this is why, you know, it's so hard to understand. I think there's a big spectrum of disease here like all of these things that can cause you to go into NSAID renal failure. They can cause just a bit of blood in your urine. So it really depends. There's no one way these things tend to present. Um they have a, they have a set of symptoms, but the severity is what I mean can vary massively between them, which is why it can be a bit difficult to understand. Um basically big proteins, big complexes which are basically proteins. It's just um an antibody attaching to an anti gen which forms a big complex or you can think of it like a big protein damage is too small, delicate blood vessels of the kidney. That's how I want you to take a concept from all of this because that tends to be how this works. So, starting off iga nephropathy, most common cause worldwide would make sense because it's an infectious cause. So it's after a group, a strep infections that strep pyogenes, that's your nasty strep. The one that's built, that's um causes it behind many, many things. So, strep throat, uh scarlet fever, rheumatic fever, iga nephropathy workers. Um not that Henoch Schonlein purpura. Um I've said rheumatic probably if you are um neck fascia, a bunch of other things. Basically strep pyogenes group, a strep very bad stuff. Um And that's the one tends to be affected with secondary conditions, but 1 to 2 days after a strep infection, A for acute I G A for acute. So 1 to 2 days. Okay. That's how I distinguish this from post strep glomerulonephritis, which we'll talk about. Next. You get it because of deposition of I G A immune deposits within the glare ELISA, as I said, big proteins destroy fucking up your primary life, fucking up your filtering, damaging the kidneys. That's how this happens. So on immune, for essence, you see I G A immune deposits, you see them in the mesangium, them. So in that extracellular matrix that connects all of the burials together. So that's how we think about this. One third, get better, one third, get CKD, one third need dialysis, basically get acute renal failure. Um less important but to get concept of how this content to go and that's the sort of level of detail. You need to know about your meter that much, but you need to help distinguish it basically post strep very similar to after a group, a strep infection but wanted two weeks rather than 1 to 2 days after. Okay. So typically will be the have a sore throat that we go. Now they have blood in the urine. So it's thought to be due to antigenic mimicry and immune complex deposition. So your immune system starts to react to your kidneys because they think it looks like the antigen of group a strep basically. And that causes all the issues. So on blood, you might see a reduced C three U C reduce the three cause immune complex mediated C three and immune complexes go hand in hand and you see a raised antistreptolysin. Oh because you have a strep infection basically. And after those few weeks you have the raised tighter. Whereas in the previous 11 to 2 days, it's a bit too acute for that. I think on immunofluorescence again, you see immune complexes because immunofluorescence is for immune complexes. And you see granular I G G deposits in the basement membrane this time. So I G um which you, I guess you can think is I G M is the more acute antibody I G is. The later one says how you can distinguish again later versus earlier for I G A supportive management. Not too much to be done. Um you don't need to know too much about the management anyway, I wouldn't worry about it, but so rapidly progressive or crescentic. So again, crescentic, again, it forms a sort of umbrella of several conditions. All that presented with that crescentic and rapidly progressive are basically synonymous. Lee mean the same thing, it describes the most aggressive form of cholesterol arthritis which causes renal failure within a very short timeframe. So it's characterized by the severity by its severity and the presence of what's known as crescents. So if you look here, you see that nice pink glomerulus before and you see this weird blue thing, this blue like half moon shape, that's why they call it crescentic. Um And that's, that's in the bowman space where you'd be filtering, that's macrophages, macrophages, let's do with inflammation as well. Talk about later. So again, this is an umbrella. It's not a disease in and of itself, it describes a set of conditions that have a very acute onset and a high severity. So you have anti glomerular basement membrane disease, which you remember from the third year. That's um good passengers, immune complex mediated pouchy immune, which basically just means anca associated, which is vasculitis and again, immune complex mediated is again an umbrella of conditions. So that's why I mean, this can get very confusing, which is why it's important to distinguish what's actually a disease in and of itself and what refers to a wider basket of conditions. So if we look at good pastures first, so the presence of anti glomerular basement membrane antibodies. So you can see here on this is what immunofluorescence looks like by the way. So you can see the glomerulus, it's uniformly lit up around the whole thing. That's because you have antibodies to the whole membrane. So it's a very even sort of picture. So on like microscopy, you see the crescents because it's so acute because it falls into that sort of previous category. And on immune inflorescence, you see linear deposition, which basically just means very regular deposition of I G in the basement membrane. Um And you also see pulmonary hemorrhage, that's just something you to know. It's just good pastors just start your stuff really immune complex mediated. So again, a basket of conditions. So what you can see here is it's much more, much less smooth. Um It's kind of as you would remember a bit spikey, a bit bumpy. Um So things causing immune complexes again, this is uh it's very complicated because it heralds back to some of the other things you have iga nephropathy, post infectious. That's that I G G immune complex HSP, which is again related to strep A and sle which is um when your body basically forms immune complexes with nuclear debris, which I can talk about if that hasn't been explained to you guys already light microscopy again, crescents the same for all of these things. And on immunofluorescence, the bumpy deposition, you kind of see it here. Kind of makes sense immune complexes in your mind. That kind of little bits spikey bumping. That's how I think about it, deposition of immune complexes in the glare. A basement membrane for the mesangium. Basically. Somewhere in the glory list, um you won't need to, you won't be asked to distinguish where basically, but yeah, patchy immune anca associated are the same thing. So something has to learn. See Anchor is G P A P ANCA is M P A or E G P A. There are other names Wagner's Chuck Strauss. You don't use them anymore. I don't think they were Nazis, but I think that they just want to move away from eponymous things for good reason. To be honest, vasculitis. Um These are small vessel vascular disease. There's big, medium small, probably has been covered in the previous hist a path. But essentially these are the micro ones. They affect small blood vessels, delicate blood vessels. Think about weather's might be within the kidney and the glomerulus, but also in the lungs um where you get pulmonary hemorrhage as well. So that's why you see the pattern that you do in these vascular titties. Again, on histology like microscopy, crescents on immune, if you're essentially no immune complex diskettes, not immune complex mediated and you might see some other vasculitic symptoms such as pulmonary hemorrhage or with skin rash as well. So that's kind of how you differentiate those things. Really, it's about understanding why the why having idea of why they happen, not fully understanding by having idea why they happen, which can help you to distinguish them better. So now we can talk about about Alport Syndrome. This again ties in slightly with Pedes. So it's a hereditary cause of glomerulonephritis, um or renal failure rather. So you have excellent gene causing a problem with type four collagen to have tried of symptoms. That is nephritic syndrome, lens dislocation and bilateral sensorineural deafness. So, eyes is and kidneys. Um kind of a weird one comes up again in final year, but something to know it's excellent. So it affects generally boys. Um and it's progressive causing end stage renal failure in young adulthood. That's about all you need to know in my mind. Um That's just to distinguish it from the next thing which is benign familial hematuria quite similar, which is where I can get again a bit confusing. So it's also a problem with type four collagen monogenic again, but this is an autosomal dominant um gene in the same collagen, a different subtype of it, but don't worry too much about that also called thin basement membrane disease. And all it causes is a symptomatic hematuria, no other issues generally. So you have this which causes progressive end stage renal failure with a few extra renal symptoms as well, mainly around the eyes and is, and then you have this which is basically just bloody urine, no other issues. Um and that's how you distinguish it, I guess benign makes sense. Benign, familial makes sense. Okay. So moving through to the tubules, um acute tubular process is something that confused me for a while up until 25th to um. So most common renal cause of AKI all that means is damage to the tubules. So, necrosis, cell death, tubules, tubules basically, yeah, tubular cells. Um so the tubular cells die and shed into the into the tubules leaves the presence of brown costs in the urine. So brown because, well, I guess you can kind of think about it like um it should, they should be ajinomoto set but basically brown necrosis dead. So think about it like that and that can be caused by many things. The key wants to know about very simply hypovolemia. So not enough blood to the kidney means you can't get the supply, which leads to ischemia, which leads to cell death. And it can also be caused by direct toxins. So some to know aminoglycoside antibiotics, the way that I would remember that is gentamicin. You kind of remember gentamicin quite a nasty antibiotics tends to mess up a bunch of things like your ears, your kidneys, all that. So nasty antibiotics. Um My glow been so again, big protein charges to the kidneys, messing everything up. Um That would generally be due to rhabdomyolysis. And also IV contrast which again, the third year thing are finally a thing, something to know about acute interstitial nephritis. Very similar but very different. Sounds very similar is actually very different to think of this as an allergic reaction. So you see an interstitial infiltrates, this is the interstitial which is basically the stuff around the tubules. Um you see an infiltrate of cells and eosinophils. So eosinophil's allergic, that's how I remember it. And these get excreted as white cell casts or white cells in your in with no infection. So no nitrites, no blood, slightly sterile pyuria. It's what they call that and essentially um think about this way. So, necrosis, brown muddy casts and intercession, arthritis, white cell costs. So basically white cells have been excreted because they're present in large amounts in the kidney most often in response to starting at drugs. That might be nsaids. That's often penicillin and it could be things like amp allopurinol as well. You might also get some systemic symptoms such as a fever or rash, which are also common with other allergies. And you can also get a form that's called chronic interstitial nephritis, which is basically an old people. After you take parities, more incense for ages. Eventually you develop a kind of weird allergic reaction to it. Fine. Um There's some stuff on blood vessels. It's all from third year. I'm not going to cover it. Um I'll just have the slides in here, basically March heart's a hemolytic uremic syndrome. Very quickly E coli 0157 H seven, you do need to know that after petting zoo, after about of diarrhea, basically leads to micro clot formation, which means the blood vessels are forced to these tiny clots, which means that um they're shared their broken down into tiny fragments called schistocytes. Um which is where you get the hemolysis, which is where you get the anemia. So again, it kind of makes sense in the name. Um as a result of this, you get basically, again, think about those delek blood vessels, you gain these tiny plots in the delicate blood vessels, breaking down your blood vessels, which causes renal failure, also causes other symptoms or from a kidney perspective. That's we're worried about the renal failure. So that's what SUS is essentially TTP is the same thing. But for different reasons that's doing an enzyme called Adam T S 13, you probably remember. Um and in this one, you get the same thing in the kidney, but you also get in tiny vessels in the brain that happens, which means you get some um neurogenic symptoms as well such as seizures or reduction in consciousness as well. So that's a brief overview, the slides will be sent out. So I wouldn't worry too much. Um It's all 30 of stuff should come back to you. Hopefully, fine, let's talk about a few other things. Now, a few of the small print. So polycystic kidney disease, this is autumn dominant do two mutation in the PKD genes. So very easy to remember, including for something called policy system. Again, quite simple to remember causes kidney failure and hematuria and also kind of big kidneys on examination. So I'll be a key extrarenal manifestations. I want you to know about. So liver cysts and the most common. But the thing that comes up in SBS all the time is berry aneurysms leading to a sub arachnoid hemorrhage to something that does sometimes come up. Um is lupus nephritis. Um I don't know why, but it does, again, this is something where the severity really does vary, which is why the staging pro program, but essentially lupus immune complex formation deposition leads to damage all throughout the body. That's why you get so many symptoms. Um It's damaged due to immune complex deposition. So again, you see lumpy immune complex deposition and this thing called wire loop capillaries, you just need to remember that. Um I think it's just a description of what it looks like on after it's been damaged. But there's a staging system, six stages. You can just learn that the most important thing to remember is that in the early stages, when it's the least severe, you have only Mizan Juul disease. So you only have connective tissue disease. It's not actually affecting the glomerulus, it's not affecting the functional units of the kidney itself, just the sort of connective tissue. Then you get deposits of immune complex within the actual kidney structure itself, which causes damage as, as would make sense, more severe lupus nephritis, as you say, lupus nephritis is just I think kidney damage related to lupus. And then once you get to the end, it's advanced sclerosis. Remember like cirrhosis, like liver cirrhosis sclerosis, fibrosis, scarring generally always towards the end of the process when there's been more damaged. And the key thing here is that 90% figure that's the end stage. And sometimes they ask BSA is about that. Sometimes they ask questions about that. Um So MS angio early stage and stage greater than 90% that sort of key a key thing to keep in mind. So just a few sbs now a few sbsf U V S A S. So if you go on the mentee, so I have that open for you now. Um So him antibodies to the foot possibility pays 82 receptor are associated with which form of colonial nephritis. And once we get a few votes, I will just um well, I'll let you know, I'll reveal the answer and talk you through it if we've forgotten, deepen. So let's see what we have. Oh Okay. Um So it's member this, so essentially if we go back here, so I'll talk about what, why things were wrong first as well. So if you remember crescentic is not a condition in of itself, it's just a bundle of conditions. Um And that's the same thing for rapidly progressive. So they're very, they're very similar. They're basically the same thing. Minimal change is associated kids has no antibodies really related to it. Um And good passengers is anti glomerular basement membrane antibody rather than um possible based A two. So that would be mem bring us and if we go back to the slide here, so it's sle and anti phospholipase A two antibodies. So against antibody mediated. So you have that classical picture on histology. Sambou is the next one. So which is a characteristic histological finding in the kidney biopsy of a patient with multiple myeloma. If you have a look here, I'll just leave some time and then we can talk about this one as well. Okay. Very nice. Um So the top answer on this one is amyloid deposition. So that's correct. So I will briefly talk about that as well. So, immune complexes um although multiple myeloma does produce a lot of antibodies, they aren't necessarily blending into anything. Um So you don't really get immune complexes per se Bence Jones proteins you would see within the urine, but they aren't the thing actually causing the damage itself. Diffuse chaotic change. I just uh that, yeah, that's just not part of it. Um And none is just a dummy answer. So, yeah, amyloid deposition. So it's one of those secondary causes and as you remember, it's a l amyloidosis as well. Great. So now the essay. So we have a 40 year old lady presenting to GP with massive protein area. Later, a renal biopsy reveals one capillaries, immune complex deposition and sclerosis, affecting Greece and 95% sample. Under which stage of lupus and arthritis would she fall so fine? Just okay. Okay. So the right answer here is six. Um So remember there's 123456 stages, basically six end stage greater than 90%. That's the real sort of things can distinguish it here. Um I have it all here. This is something a bit tricky. It's not, well, I think it's not very high yield, but it's easy to understand. So I would have an idea of it. I wouldn't heal myself learning the specifics of it, but it does tend to come up for some reason. Fine. And another VSA now, so a 25 year old man is involved in a road traffic accident on arrivals, BP, 65/40 but it's quickly resuscitate and stabilize in I T U. Two days later, the Shn notices over the past six hours, his catheter urine output has only been 50 millimeters, which color is the urine likely to be on microscopy. Okay. Mhm. Oh Yeah. So the answer is muddy brown and why is that? So basically, that's the next question. So let's ask what's the cause of his actual renal dysfunction. So again, you just answer that and then we'll talk about what's going on here. Okay. Yeah, great. So it's acute tubular necrosis. So basically what's happened here is we have a man who's been in our ta who's lost a lot of blood, most likely who's lost profusion to his kidneys, which means that his kidney cells decided to die being shed, which what produces the muddy brown color, the muddy brown casts um and causes his renal function to decline. So often the picture that you get is someone who's had a pre renal AKI you rehydrated them, given enough fluid that's stable now. But then the renal function continues to decline. And that's because you can't reverse the grossest. Basically. Um They've progressed from previous all AKI to 80 N and that's the way to think about it. Um Just a refresher slide, but I think most people got their rights are very good and this is just what those costs look like. This is what they mean when they say muddy brown. And that's sort of what the cost looks like basically just to sell, which has been forced through something fine. So moving on to the next thing which is liver. Um this is the one which is covered by Rob Gordon himself. I think it's quite good to know about. Um And I think it does help to kind of understand a bit better for final year as well. So this thing to start off with, I guess is the anatomy which actually does help in this case. So you can kind of think about the whole liver as, as formed up of a bunch of hexagons within which there's loads of cells. So you have this what's known as a functional units. The functional unit of a kidney is a nephron, that whole system. And the functional unit, the liver is basically these things called sinusoids, which is these hexagons hexagonal structures. So at each pole of the hexagon or each corner, you have um these sort of bundle of vessels called called the portal triad. We have an artery, a vein and a bile duct. And you have a central vein in the middle of it. Essentially, you have flow of blood into the central veins and arteries, vein that kind of makes sense. Um And then blood here gets filtered of toxins. You have the hepatocytes which essentially a metabolically active and break down all your toxins and you have direction and you have bio flow the opposite way. So you have it from the central vein out to the portal triad as well. Um So zone one is around the portal itself that's closest to the blood vessels, which means it gets the most oxygen because it all travels by diffusion. Um And because it's closer to the blood, it will be the first thing affected in blood borne illness such as viral hepatitis and toxins. So into is the middle zone, sort of around one is closer to the central vein. And so in three is actually actually around the vein itself. This is where you have the highest concentration of your functioning hepatocytes, which means you have the most liver enzymes, the most metabolism, which means it's most sensitive to metabolic toxins. So if you remember, paracetamol is not actually toxic in them itself, it's broken down into something which is toxic, which is why it causes the most damage around. So three, we have the most metabolism. If that makes sense, it's also it's furthest away from the arteries, the least oxygenated. So if you take a big ischemic hit, that's the area that's going to be hit first. So those three causes of really raised transaminases are a big ischemic hit, viral hepatitis and also toxins like paracetamol basically. Um and this is the zone of flow. So from porter tried to the central veins and blood essentially trickles in the spaces between these hepatocytes being filtered towards the central vein. This is what it actually looks like. So you can see here you have this little weird hexagonal structure. Don't worry again about it. I just want you to get an idea to have a look in your head. Um acute hepatitis, this caused more things this can be caused by things like viruses. So most often hepatitis A and B, which are your fecal, all roots and also drugs. So the pattern of information which all gone does want you to know about is spotting necrosis for acute hepatitis. This means small areas within the sample of inflammation and necrosis with inflammatory infiltrate. Anyway, you get inflammation, you infiltrate of white cells basically to deal with it. And chronic hepatitis, that's also viral but not have a or e more generally that we have to be your HEP C also drugs and also a bunch of other causes such as PB, CPSC Wilson's and hemochromatosis, which you'll remember from third year as well. The pattern of information here is different. So for acute spotty and here you have this thing called interface or piecemeal necrosis. Um that basically means you have more widespread inflammation and you lose the border between what's known as the portal tracks and then actual liver bits itself. Um and you also get fibrosis eventually. So chronic hepatitis just means chronic inflammation of the liver, which leads to fibrosis, which eventually leads to cirrhosis, which we'll talk about as well. Um And you get this thing called bridging fibrosis, which I will show you gonna slide here. So, the way to think about fibrosis, the past like damage, at least necrosis, the fibroblasts replace these dead hepatocytes with fibrotic tissue because that's all they can do. Although that, although there'll be some areas of regenerating hepatocytes as well, and they referred to as nodules of regeneration. So, micronodular is alcohol, micronodular is every other cause. Basically. Um rock corn again wants you to know that I'm not too sure why they can come up because of the increased amount of fibrotic tissue because the amount of scar tissue, this is obviously a bit tougher than usual hepatocytes. You have increased resistance to blood flow because as I said, the blood flows through the tracks in between cells. So if you have scar tissue there, instead of a gap between the cells, you have increased resistance, which leads the backflow of the blood. If you think about the whole system, which leads to portal hypertension and then increased resistance also causes fibrotic bridges. So blood always and any fluid, I guess flows through the path of least resistance. So eventually it will form part of less resistance than going through the fibrosis will go over. What that means is, it doesn't flow in between hepatocytes anymore. So you don't get any filtering going on, essentially bypasses the hepatocytes, which is referred to as an intrahepatic shunt intrahepatic because it within the liver, the functional units of the liver itself because of portal hypertension. If you think about that, um essentially portal, the portal vein brings blood upon the gut into the liver to be filtered. So if the actual filtering system itself, so you have the big vein breaking down into the filtering systems. If you have increased pressure within the filtering system, that goes higher up the pipeline into the actual portal vein itself. If you have hypertension in the portal, you have hypertension, you have a higher BP essentially within other vessels within the body which causes what's those extra pathic shunting because the backflow of blood, these big veins, big vessels. So that's when you get esophageal varices in erectile viruses. And also keep it may do side all of these things, just big vessels when they shouldn't be basically. And then this is just an illustration of it. So you can see here, normal looks very nice and you have this weird scar tissue, eventually you get these bridges forming, which bypasses all these nice tracks. All these nice cells that usually passes through. You bypass that going straight to the central vein path of least resistance. Eventually you'll be more widespread. And then you get cirrhosis, which is where the whole structure, whole sort architectures completely broken down such as an illustration of what's actually going on. So in terms of alcoholic liver disease, there's three main histological patterns to know about. There's a few sort of keith findings in each one in the cells. So the starting stage is hepatic steatosis. This can be sort of stable disease. It's fully reversible. If you avoid alcohol. And if you've had a heavy night out, you're going to have this on, on your biopsy. So you the big pail greasy fatty liver and you see fat droplets in the pad sites. So quite easy to understand you have alcoholic hep a hepatitis. Yeah, but again, a large liver, but against some fibrotic change, this is more chronic alcoholism, more chronic damage. So the past sites start to balloon. So they get, they gain fat, they gain water, they swell up, get this thing called things called mallory denk bodies. And this is mainly zone three damage that's closer to the sorry to the central vein further away from the actual blood vessels. Again, that's because there's more pesticides, breaking down the alcohol into the toxic byproducts which damage the actual liver cells itself and that damage starts to lead to fibrosis. But this is not cirrhosis. That's the one thing distinguished. Then you have alcoholic cirrhosis where you have instead of a big organ, you have a small shrunken fibrotic brown one. And there you get what's known as micronodular cirrhosis that's referring to a small nodule of regenerating normal mentis sites. But by and large, you just have fibrotic tissue which isn't functioning. So, scar tissue fibrotic tissue. This is the same for any organ when you have damage, nonfunctioning, not as good as actual parenchymatous or actual functioning tissue itself. And then some other liver conditions, I'll briefly talk about all of this stuff is from year three. So NAFLD is basically fatty liver disease, nonalcoholic fatty liver, very similar to alcoholic liver disease. You distinguish it based upon the history. So basically, it will be in someone who's quite fat obese with diabetes or metabolic syndrome essentially. And the progression is very similar. So hepatic steatosis, then nonalcoholic steatohepatitis instead of alcoholic hepatitis. That's the sort of switch switch out but very similar. And then cirrhosis is the end stage as well. PSC is more common in males yet fibrosis of the interim extrahepatic bile ducts. Um and that's associated with anchor, also associated with ulcerative colitis and gives you increased risk of cholangiocarcinoma. It's the way to think about this. I guess you have sclerosis. You have inflammation of the bile ducts, the bile duct, um related to gallbladder, which is related to cholangio carcinoma. PBC is more common in females and autoimmune process not necessarily inflammatory. Oh, I guess it is inflammatory but associate with the autoimmune side of it. If you remember immunology, there's autoimmune and autoinflammatory. It's more on the auto immune side of things associated specifically with antibodies. So, antimitochondrial antibodies and affects the bile duct with granulomas. An autoimmune quite simple to remember just an antibody to remember. So young postman or postmenopausal females with other autoimmune conditions such as vitiligo thyroid issues, stuff like that. And you have anti smooth muscle antibodies or anti LKM antibodies. So that's type one and type two. Type one being smooth muscle, type two being anti LKM. That's all you need to remember about that. Really. There's Wilson anti and and heretic hemochromatosis and also alpha one antitrypsin deficiency. Um I won't run through this too much. Basically what you need to know here. All the buzzwords very much. You have three stuff. Um So I'll just skip over that as well in the interest of time. So if the liver of some malignancies, the most important thing is to outline here is that the most common form of malignancy is a metastasis, then you have HCC and cholangiocarcinoma. These actual malignant forms, cholangio carcinoma often associated with PSC. And don't worry too much about astrology butts. Their HCC is with the tumor marker AFP. And there's a bunch of causes, basically any chronic inflammation leads to fibrosis, leads to cirrhosis and inflammation also lead to damage, which can lead to cancer. Essentially benign. A few small things very, very minor, just have an idea about them. So, liver, liver as enemas associated with the OCP him angiomas, most common form benign can cause some bleeding can get removed. They're too big, that's about it. So, um onto the liver. So if we do a few SBS for this. So a 36 year old woman with the history of hypothyroidism was seen in the clinic following abnormal routine LFTs liver biopsy revealed a loss of bio duct with granulomas, which characteristic serological marker is likely to be raised if we just get the results here. And this is quite characteristic of some of the questions you will get in past. Basically a pick your, pick your own of an antibody, which is, yeah, it's okay. I guess it's a nice question. Um To, to be honest, after you revise fine. So, yep, majority went for antimitochondrials. That's true. Again. Just something you need to know I think in the path guy, there's a big list of every antibody what it relates to. You do need to miss the final year. You did learn this during the third year, most likely. So it all links together and it all does help. So next, what is the inheritance pattern of genetic or hereditary hemochromatosis against quite a characteristic question? Often this sort of thing does come up. I think it's actually stripped straight from a past paper and this will just be going back towards um third year again, just waiting for a female. Okay. So I see what people think. So. Yep. So we have a few for also going to mostly recessive. So again, it's just something you need to know, autosomal recessive. Um for hemochromotosis also an obsessive for Wilson's disease, which is the little one to copper and iron and an alpha one antitrypsin is dominant. So generally, I think the way it's, it's a bit of a rule of thumb. But if you have to guess, then more severe things tend to be dominant. Um and more less severe such things you can live with long term tend to be recessive, but that's a very, very broad rule. So don't, don't quote me on that, I would say just learn it. Um What is the most common examination finding in a patient with portal hypertension? And this is very important for final year as well to distinguish between, that's, that's sort of distinguishing between um stable hepatitis and destabilized um or exacerbation of stable liver disease. So those who do you think? And you kind of hopefully see what I mean when, when I say that histo is just medicine, so see what we have. All right, this one's very split actually. Um, well, very but quite split. So we have splenomegaly and spider neophyte as our too. So the correct answer here would be splenomegaly. Um So the reason behind that, so liver flap, yes, you can see it that's caused by excessive diarrhea when essentially your liver is just straight, not breaking things down too many toxins. So you can see it but it's not very common. Um joined this again, you can see but less common because if you think about it, what does portal hypertension mean? In this scenario, portal hypertension means you have unstable liver disease. So the signs of stable liver disease are those classic things. Palmer erythema, it's clubbing, it's spied an IV I it's um all your other sort of classic things like do better and stuff like that. Um Whereas unstable you have portal hypertension and all your, all your relevant stuff. So it's soft, your varices, um you have cap it, medusa, you have jaundice. But the key thing here because in anyone with portal hypertension again, think of it like a circuit, think of it like a pipeline, the spleen is directly within that whole thing uh within the whole system within the blood vessel system. So, backflow results in a big spleen pattern megaly you wouldn't get because in later stages where you're actually at this stage of like quite developed chronic liver disease, you have a smaller organ, that's the thing to not get caught in there. Um And so that is why that is the answer. So, next one with the liver biopsy of a patient reading spotty necrosis, which pathogen is the most likely cause. Let's see what we got. Okay. We'll just wait a few more. Okay. So let's see where we go. Yup. Pepe, great. So, very good. So, acute hepatitis, the key thing, they're spotty necrosis is acute hepatitis. And that piecemeal interface is the chronic and acute would be hep A. So all these other ones TB can cause everything. Um always a good answer to be honest. But that would be, wouldn't be the typical acute picture B and C more chronic again, HIV not really relevant. Fine. So a 23 year old medical student has just returned from his elective um in Tanzania where he swam in Lake Malawi. Following this, he develops fever, wriggles, hematoma, Ghaly and hematuria. What are his blood tests most likely going to show? Let's see what we got here. Okay. All right. So that's what we think. Okay. So you have 50 50 raised the of senna pills and deranged thirties. So I think this is a nice little lesson um in SBS. So there can be, this is something which it took me a while to get my head around. There can be multiple right answers um in an S B A but you just need to pick the one which you think is, I guess the most right, if that makes sense. Um So in this case would be raised us nfl's why. So basically what I'm getting at here is my guy has schistosomiasis, um which you get from swimming in Lake Malawi goes through your skin. He can have meant multiple of these things. So you can have to arrange. Altes, got some liver involvement. He probably has some deranged using these as well. She's hematuria, but with any parasitic infections because you're, unless your immune system is completely defunct, any, um, parasitic infection, you will absolutely have razia cinephiles. So that's why that's sort of the most corrective. That makes sense. Um Although he has a pattern megaly, it's very likely is raised deranged LFTs, but almost certain if that makes sense, these razia cinephiles. So that's the answer that I would pick in that scenario. Um It's probably not that resemble another question you get in path, but it's more to prove a point. I guess that you can have multiple right answers and just go with the one that you absolutely 100% no, is always going to be correct. Um Even if multiple things that they could be correct. Fine. So moving on from there to keep blood cell types. So it's just some fundamentals. But I think it's important to understand, helps out a lot with other things as well. So, neutrophils, um hip, they're associated with acute inflammation that can be sterile and nonsterile, some utility of bacteria. Or just if you knock your, your knee, you'll get neutrophil going in to clear out the dead cells. Um So multi lobes, so dark nuclear, multi lobes and granulated, which is how they basically do. The killing macrophages are late acute or chronic inflammation. That's how I think about it. Bigger cells, lots of cytoplasm looks more like a typical cell. Um lymphocytes again, chronic inflammation, big, big nuclear here. But the main thing to distinguish is the neutrophils are really your first line acute inflammatory processes and then macrovision them sites. They're much more chronic phagocytose ing dead cells or pathogens, whatever that might be. E S nfl's parasites and allergies. That's how I think about it. Read Granules, not that important. Maybe you, you could realistically get a slide on one of these because these are actually quite um what's the word, quite characteristic these cells. So it's not unreasonable to expect something like that. And mar cells allergic reactions, lots of Granules which um you might remember anaphylaxis, mast cell degranulation, IgE mediated and that has a lot of histamine and stuff like that. So many, many radials can't even see the rest of it basically. Um fine. So moving on So another SBA, so which tumor type produces keratin and intercellular bridges. This is really um kind of a bread and butter question and something. But I think again, you could work out from first principles if you had to all the home. So you won't have to push it. Okay. So let's see where we go. Okay. So a few for basil cell mostly squamous. That's right. So squamous cell carcinomas produce keratin interesting bridges. So these are really the key to tumor types you need to know for carcinomas, which is essentially a malignancy of epithelial cells. So this table I think is in the path guides as well, but essentially squamous cells think about them in terms of your skin. So for example, if you have squamous cells within a urine sample, that's contamination because it basically means you've got um bits of debris from your skin in there, which is contaminating it. So it's to do with skin skin keratin, that's the link you'll see interested in the bridges. So that looks like this on here. You can kind of see there's these things in between the cells. Um Just think of that in terms of everything else. Uh in terms of linking with the keratin, it doesn't form glands where it happens again, very similar connective tissue, uh mucosa, things like that. So, esophagus out, esophagus, skinhead, neck, anus cervix, vagina, those sorts of places, adenocarcinoma to do with organ super glands. Okay. So, lung breast, stomach colon, pancreas, basically, organs versus you're more sort of skin connective tissue areas. Uh Don't worry too much about the picture, but just to show basically that it can produce substances like mucin. So I think that's the blue thing that will be highlighted there. Transitional cell basically, can you be kidney, urata, bladder renal system. So, renal cancer, bladder cancer, stuff like that is transitional cell. Don't worry about what it looks like. To be honest, I just had to put a picture in uh um there are many different genotypes. These are just the malignancies of epithelial cells. These ones I think they tend to ask about most cancers within histo adenocarcinomas. Just get that in your mind like gallbladder, lung stomach um about almost all gonna be adenocarcinomas fine and then H and E staining. So this is just some, just a factor. Know really the mainstay of any stains that classic pink picture is H and E H or hematoxylin stains. The basic parts purple and E stains the acidic parts pink. You actually need to know that I think but just know the name of this stain because sometimes they can ask it as A VSA. Um I'm not sure they actually teach it to you anywhere but it's just something to know. So a 40 year old man presents the E D complaining of five hours of central crushing chest pain, E C G shows ST elevation in these 23 and aVF, what changes would you see on histology for this man? Let's see what we think. This is quite an important one to know about this topic. I think it seems to come up most years, definitely came up last year. And again, it kind of ties on to those principles of how inflammation works and the whole process as well, similar to how it works for the liver. So again, you kind of work things out from first principles. Let's here we go. Okay. So it's kind of split quite evenly actually. So we have necrotic cell death, loss of cardiomyocyte, nuclei, polymorph, infiltration and none and all kind of levels. And the correct answer is none. So this is a question of time scale, right? So we have an ST elevation and my blood flow completely cut off to a certain region of the heart leading to necrosis. But what we do is we work on time. So under six hours, absolutely normal. So you have no race CKMB, you have absolutely no changes. If you take a biopsy and have a look, that's the key thing to know then within the first day. But after that six hour mark, you have the first changes, you have some necrosis, you have loss of nuclei and something called homogeneous cytoplasm. I think that just basically means that um a prognosis is starting to occur. So this is when the cells are actually dying 124 days in the acute phase straight after the cell death, you have infiltration of polymorphous, then macrophages to remember, neutrophils acute. The first line, the first responders which go to clear up your debris, eat all the dead stuff. So if you think about apoptosis sell, explodes, release a bunch of crap into the, into the heart, into the interstitial in neutrals come eat all that up so it can be replaced back to normal macrophages come after that. And these all up phagocyte which clear up debris. Then after that four day mark your next stage, 5 to 10 days, further removal of debris. And then 1 to 2 weeks later, you're granulation tissues that you're starting to heal slightly new blood vessels forming myofibroblast, which essentially forming new scar tissue, which is from collagen. So you have trying to heal and forming scar tissue. And then weeks, two months later, you have your scar tissue formation and you have sort of re strengthening of the heart. It never really tends to function as well as it did before the M I. But that's more filthier stuff to heart failure happens. But yeah, it's an oddly important topic. I think it makes sense once you understand a few of those principles of um how information works. So basically your inflammatory cells in the innate immune system coming in progression from neutrophils to figure sites to fibrosis too well, not cirrhosis, but basically scar tissue formation after necrosis after necrotic event. Fine. So in terms of the next S P A, we have a 30 year old woman receiving results of a colonoscopy, which she, I should say has had to use a persistent pr bleeding. The results reveal around 75 polyps seen in the right side of colon. What is the mechanism by which she has an increased risk of malignancy? So, let's see what we think. And again, you can, I mean, a few steps here, you need to first work out what's going on. You then need to pinpoint within that. I guess what the pattern is. It's more of a 2 to 3 ham a question, I guess. And cancers wait for a few more. Just really. So, yeah. Okay, good. So I think most people seem to have gotten that this was um HNPCC or Lynch Syndrome rather than F A P. Um And that is autosomal dominant. So we'll talk about that all those now. So, familial adenomatous polyposis, think about the name familial, basically hereditary monogenic adenomatous loads of adenomas and polyps, loads of polyps. Um So basically this is in a tumor suppressor gene autosomal dominant mutation. It presents with hundreds or thousands of polyps. So that's why it wasn't F A P in the previous question because you'd really be seeing in the hundreds or thousands, not just 75 polyps. Um If you don't treat it in childhood where you often find it, you get adenocarcinoma early adulthood, 100% chance often basically the key for these familial bowel cancer syndromes is regular monitoring with colonoscopy or flexi sigmoidoscopy and then eventually it collected me usually. Um but if you remember, you have that kind of progression from an adenoma or a polyp into an adenocarcinoma as well. Then Gardner syndrome is another one that's a subtype of F A P. So it's the same sort of autism or dominant mutation and tumor suppressor gene with extra intestinal features this time. So you have tumors in the skull, epidermal isis desmoid tumor, sort of more skin focus things and dental caries for some reason, I'm not too sure why, but just think about it as fap with extra g eye manifestations as well. You have Lynch Syndrome or HNPCC, which sort of ties in with dining as well as an autosomal dominant mutation in A D N A mismatch repair gene. So, a tumor suppressor gene, you have a problem loads of polyps. This one, you get less polyps, but because you can't fix those defects in the polyps that do exist, you have a more increased chance of progression of any individual polyp to a cancer. Think about it that way. So the tumor suppressor suppresses polyp formation, you lose that you have loads of polyps which then and eventually each individual one has a low risk of progression. But when you have that many, one of them will progress. Whereas this, you have less polyps. But because you can't prepare faults within the cell replication. When an error happens, each individual pull, it has a higher chance of converting to cancer. That's how you can think about it. Also, this is associated with extra colonic cancers, most commonly endometry als but also ovarian small bowel and gastric as well. So this is just a table summarizing all of that for you guys to look at if you want to later. Yes, key thing for all of them monitoring and eventually a collectivity, but that's more final year staffing. So gi polyps just a bit on this sort of higher risk of cancer means is when you have a larger polyp, when you have more polyps, higher village component or higher amount of dysplastic features to dysplastic, basically, meaning that it doesn't look like a normal cell for that area. The most important one of this I think is a larger polyp. Um So if you have to choose between these choose larger um or more, but that they don't tend to be together, you usually have to choose between larger or things like villas components. Um So normal cells go normal to an adenoma to an adenocarcinoma. And again, almost all visceral cancers are adenocarcinomas except except for those more specialized ones like renal cancers and stuff like that. Um So you probably see the progression here. So you had the abnormal formation and eventually that forms of cancer and then you can see here the difference. So polyps, you have tubular, which is this more sort of classical um podunk elated form and then you have your more villus kind of both individual components if that makes sense and you can have, have a middle ground in between them. And that's just to demonstrate the difference in what they look like. So you can imagine them basically. So for via sake. So a 64 year old lady who's been diagnosed with men to a um fine mental evidence with forward lump further investigation reveals a malignancy, which hormone would you measure to assess response to treatment? And the point of this is basically to ram home. The fact that you guys need to remember what the difference between all the men's are an unpleasant bit of third year, but very important for this actually because you can come up and it crosscuts between all the different bits of path. But I think because this is a VSA you get a clue because there's only really one or 21 thyroid malignancy where you actually imagine a hormone, I think he's always wait for one more month. Then we'll see. Okay. Right. So this is the calcitonin. So the reason behind that if we move on to the next one, so this is just all your men's um is you have medullary thyroid carcinoma, medullary um is the one where it's done. It's pretty, it's a basically a tumor of the parafollicular see cells. Um You just need to remember that, but basically see cells see calcitonin, that's the one that you measure. And I guess parafollicular similar to parathyroid related to calcium calcitonin related to calcium. The way I always remember this was it three PS going to, to PS going to one P and then more M's as you go as well. So it's the parathyroid, the pituitary in pancreas. So it would be things like an insulin oma or a glucagon oma. And then it goes to, to P Sophie, oh and the parathyroid and went on the, the thyroid. So all around the thyroid and that meant to be you have those acoustic neuromas. You have your medullary thyroid carcinoma again and your fairs again. But you also have the marfanoid thing but basically three ps two piece, one piece that's hard to breath. But you do need to know this and it does help you a lot. Um in path last topic to cover is a bit of a weird one. Um This came up in the, some of the mocks and some of the things last year during my revision, which is why I wanted to go over it. Um ok, solamente seems to have decided doesn't want to help, but if you just have to think about it, so essentially um absense with symptoms of nocturia, poor stream, terminal dribbling and weight loss biopsy. And histological analysis reveals the offending malignancy reveals 60% of cells are grade three, third percent grade four and 10%. Grade five. What is his Gleason score? So Gleason score NG is something that they want you to know how to do, but it's actually very straightforward. It's just something that you might not have heard about. Which do I want to cover it? It's actually not something in third yet. So I'll give you a few seconds to think about it and if you don't know, then think about how you would approach it because there's a non zero chance, there'll be stuff you can't deal within paces in path and having a system to deal with it. Having a methodical way which you would go about, it can help a lot because a lot of this stuff does make sense. And if you don't know what's better in a vie ver in, in either path or in paces is if you're able to kind of work out something vaguely logical, you'll get, still get a higher mark than someone who kind of just says, I don't know. And then just shuts up because they'll think you're a smart person and paces is all done by vibe. It's all global ranking now marking that rather. So the score has eight. Why is that? So let's talk about one. So prostate cancer again, commonly adenocarcinoma, like any glandular or visceral cancer in the peripheral area of the gland and then you stage by a biopsy or histology as you always do. Really. So 125 based on differentiation for each one. So you take basically take a sample, you look through a microscope, see what's the worst grade. So the most severe bit of cell, so what's the least differentiated, the most aggressive? And you look at what the most common grade across the entire sample is. Um And then you take those two numbers, so you the grade of the most common type of cell and the worst cell single cell that you see. Um And then you add these two numbers together to get a result out of 10. So you expressed this is X plus Y equals E. So for example, this one, it would be um yeah, so be three plus five equals eight. That's how you express it. And that's Gleason score ing very simple. Just something you may not come across. So if it does come up, you have an idea of how to approach it. That's the main thing. And as I said, like look a lot of this stuff like PBC PSC all came up before. You don't need to know much more than you did in third year. It's just revision. So I mainly wanted to focus on things which you might not have come across before. Just so in the off chance it does come up, you can address it and so you can start to think about how you might go about these things. Um So in terms of closing points path, it's not as bad as it first seems once you start revising and honestly all starts to link together and it starts to feel, you start to feel a lot more confident about it. 50 is hard. It's a big slog, but it does pay off. It's the hardest year, I think in terms of how long it is, you're probably getting towards the point where you feel similarly. Now, final year is very short, very nice. Um It's not nice but it's short. Don't forget to enjoy your life. There's more to life and exams and rankings. I mean, they're probably gonna do away with all that anyway. And last thing is there's gonna be more strikes almost certainly. So don't support, go support your um coworkers cause these are the people are gonna be teaching you the fighting for your future. So make sure you go to the picket line and show your support. Last thing, be nice to each other. Um There's a lot of toxicity in medicine and Imperial and don't add to that, you know, share resources to each other and just be nice. Fine. Um So I'm happy to take any questions I will stick around uh until that aren't any, I guess um literally could be about anything to do the path to do with Histo to do with other bits of path. If you have anything you wanna email me, feel free, happy to explain what I did or anything about fifth year final yet any of that. Um And obviously there's plenty of time now that everything's over. So yeah, any questions let me know otherwise. Thank you very much. Love it, Johnny. Thank you very cracking talk. I thought you recovered some really high yield stuff there and I thought the questions are really, really good as well, might really do appreciate it. Thank you very much. Uh If people do have questions, please put them in the chat now. Um If it's alright, you Johnny, I'll shot are QR code as well. Just so people can um put that feedback out for you. Yeah. Um There we go. We'll be able to see that. Now people can scan that. I've also put a link in the chat as well. So if you don't want to scan it, you can copy and paste the link that I put in there. Okay? Um Yeah, so I see a question. Do you recommend using the guide only to rise path of going through lecture slides? Uh I did not look at a single set of lecture slides the entire time that I I attended the lectures. Um I caught up on them if I missed them, but I never looked at them again. What I would say is day zero especially don't bother with that. It's a waste of time. Um If you ask me um what has this been? That's fine. It doesn't matter to be recorded. Uh It's a waste of time. Um I didn't look at single one. Everything used to know about them is in the path guide, probably in a bit too much details. Well, um if there's something you're not satisfied with, go through a lecture slides for it, but often they do this weird thing in path where they kind of spend like five slides going over the history of the guy who discovered it and then wasting a bunch of your time. So I think watching recording is an awful way to advise path slides is better, but they still put in loads of extra details sometimes. So I think that got enough. But if you're feeling a bit, if you're on a topic, then feel free to go through it. I would say more important for course leads though. Definitely cause they write the questions in the end. Um The other thing I just do want to share if that's alright, everyone. Um Just a link to our study. If anyone hasn't already um filled out the form, we'd really appreciate it. If you could just have a have a scan of that, look through the questions. And then if you do have time, I would really appreciate it. It's just about the teaching, evaluating how useful a peer to peer teaching has been so far at medical school and also the resources that we use as well. Just take a second scan that perfect. Now, if uh no one has any more burning questions for Johnny then. Thank you very much again for giving up your time. Best luck with everything. Jani. Congratulations again and thank you, everyone. Hope you all have a lovely uh Friday evening. All right. Cheers. Thank you.