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Guys, we'll be starting in a few minutes when a few more people join. Ok, guys. Uh we're just gonna get started now. Um ok, so today's tutorial is about everything you need to know about chronic kidney disease. And uh, so my name is Ale, I'm 1/50 student at UCL and er, Dia Dia is also with me and she's also 1/5 year medical student at UCL. Ok. Um, so a little bit about teaching things if it's the first time you've uh watched one of our tutorials. Um, so it's weekly tutorials that was open to everyone. Um, we focus on core presentation and kind of teaching diagnostic technique. Uh It's all run by medical students and it's for medical students and all of our slides are reviewed by er, doctors to ensure that they're accurate. Um And uh we'll keep you updated about our upcoming events um through email and group chats. So, yeah, you can uh follow us on medal just to kind of keep up to date with everything we're doing. Ok. So, uh my section is about uh the high yield information that you need to know to really understand chronic kidney disease. Um So I will uh just ask everyone or you can feel free to put into the chat at any point uh to ask any questions or answer any questions as well. Ok. So what is chronic kidney disease and why is it important? So what is KD? So chronic kidney disease is a long standing condition that leads to a gradual loss of kidney function over time? So that just means that over time, the kidneys aren't working as well as they should be. The reason why it's very important is because it's an extremely prevalent condition and it affects around 9% of the global population. Uh and around half of er half of the people who are over 75 have some form of C KD to kind of understand chronic kidney disease. We need to be aware of uh what the glomerular filtration rate is or G fr um you might have, you probably would have heard of this in 1st and 2nd year. Um and you would have, you probably would have heard it on the wards as well, but it's a bit important to understand exactly what it means. Um So it just means a volume of liquid that's filtered by the kidneys. Nephrons per minute. So if you, you can just see in the diagram, you probably remember. So, nephrons are the bits in the kidneys that er filter the blood uh and kind of removal of the waste products. So, this can be a bit difficult to actually work out the the true glomerular filtration rate. So we use an estimated glomerular filtration rate or EGFR and we work that out through uh using serum creatinine. Um It, this does have some limitations by using an estimation and we're gonna go, go into that a little bit later. Um But that is what we generally tend to use as the EG FR compared to the actual G fr. OK. Oh Yeah. And uh just in case you, if you're not aware, so creatinine is a waste product that is natural and it comes from uh the natural breakdown of muscles. OK. So we'll talk a little bit about C KD staging because this is quite an important concept to get, get your head around. So there's five stages in C of C KD and they all depend on the, the glomerular filtration rate. So you just kind of have to remember these numbers and uh don't worry, I know it's, it looks like quite a lot, but we'll go through a really easy way to remember all of them in a second. Um Stage one is the least severe and it goes uh gets worse and worse until you get to stage five. Uh And it's above 90 is stage 1, 60 to 90 is stage two and then so on and so on until stage five where if it's less than 15. Um something that's really important to note however, is that for stage one and two, they can only be diagnosed if the G FR is. So it's either sixties to 90 for stage two or over 90 for stage one. And there needs to be some sort of abnormal kidney test. So what does that really mean that it could be like a deranged uh urea, urea and electrolyte level, uh protein in the urine, blood in the urine or some kind of structural abnormality, uh that's detected in a scan, for example. So if you said you wanted to, it's not just about the G fr, you also need some evidence of like poor renal function. Ok. So this is a, a kind of easy way to remember the KD staging is the G FR clock. So we have like 12, 96 and three in the same place as we did on a normal clock. Um So between 9090 above is stage one, between 9060 is stage two and then, so between 6030. So three is split into three A and three B and then split at 45 which is between 6030. Um and then 50 split stage four and stage five. So that's quite a, a simple way of er remembering the, the stages of C KD. Ok. So we'll go on to the symptoms of chronic kidney disease. So they can be quite nonspecific because uh you know, the kidneys kind of affect the whole body. Um So we'll, we'll go through a few of the symptoms. So, edema because the kidneys aren't filtering the blood as they should be. That leads to a build up of fluid like ankle swelling. And you, the patient might notice weight gain, uh feeling tired, uh polyurea. So, going urinating frequently, um pruritus or itchiness and that's due to the uremia. So that just means high levels of urea in the blood. So normally the kidneys would get rid of that. Uh anorexia, insomnia and uh nausea and vomiting as well. Ok. Later on, the patient might notice decreased urine output once again, fluid overload symptoms. So, the uremic symptoms are quite important. So those are just the symptoms caused by um the high levels of urea, the main symptom and this is uh you know, it comes up in exam time. So the main symptoms or due to the uremia is nausea and vomiting. But other things that can happen are a metallic taste in the mouth, pruritus, uh encephalitis and pericarditis. Um We also have anemia and bone and mineral disease, uh which we will touch on a little bit later. Cos they are quite important complications of chronic kidney disease that uh we need to be aware of as medical students. Oh, yeah, we also get metabolic acidosis and cardiovascular disease. Ok. Does anyone want to try and shout out uh what any of these signs are we leave on, on for a minute I put it on the chart. I'm also monitoring the chart. Yeah. Give it a few more seconds. OK. We can just go through them. Um OK. So the first one is p, the next one is frothy urine. This one is uh pitting edema. Yeah. Great. Exactly. Yeah. So the last one is pitting edema. Um, any idea? Oh, yeah. Good. Yeah, perfect. OK. Yeah. So the last, the last two are uremic frost. Um an A V fistula and uh peripheral edema. Yeah. So uremic Frost is just due to the er uremia or like urea in the blood and then that leads to a crystal deposition on the skin and then good. Perfect. So a V fistula you'll see this in patients with quite severe d so probably stage five, they have to have a surgical procedure that connects an artery and a vein and that allows them to be connected to the dialysis machine. Um So that's a really important sign to, to be aware of and you'll probably see that on the wards a lot as well when you, when you do renal. Um ok. Good. Excellent. Ok. So the next thing is, so this is a uh this will be a poll. Um, what is the most common cause of chronic kidney disease? So we have hypertension, adult polycystic kidney disease, chronic glomerulonephritis, diabetes and long term NSAID use leave on for another 10 seconds. Ok. So the answer was diabetes. Let's have a look at the chart. Ok. So yeah, so more people uh voted hypertension. That's ok. Um Yeah, so all of these are causes of chronic kidney disease, but diabetes is the most common cause. Um So we'll talk a little bit about the pathophysiology of how that works. You don't need to know it in that much detail, but it kind of helps to understand um what's actually going on. Ok. So, uh before we start that, uh you can see on the top right, I've got a kind of diagram of diamerus with the afferent arterial. So that's the one that's going towards it, taking the arterial blood there and then the efferent. So that's taking the arterial blood away from the glomerulus. Ok. So, in diabetes, we will have excess glucose in the blood and that will stick of proteins. Um This will affect the efferent arterial. So the one that's going away that causes it to become more stiff and narrow. Um If this is more stiff and narrow, that means that it's gonna be more difficult for blood to leave the glomerulus, which means that there's gonna be increased pressure here, right? So, if there's like a, it's harder to pass through this tunnel, there's gonna be a build up in the glomeruli which increases the pressure and that causes hyperfiltration. Uh which means that more things er are getting filtered out than they should be. So you might even see glucose in the blood for example. Um yeah, the high pressure uh also causes the supportive mesangial cells um to secrete more extracellular matrix which leads to the glomeruli actually becoming larger. And that's a, that's an important point. Um and then the glomerulosclerosis. So the the actual glomeru is becoming larger and sclerotic uh that diminishes the nephrons ability to filter the blood. So all of these changes lead to the development of chronic kidney disease. Yep. So all the nephrons just aren't working as well as they should be. Ok. We'll talk a little bit about hypertensive nephropathy. So, chronic kidney disease caused by hypertension. Um So we have chronic hypertension which causes increased systemic pressure in the renal arterioles and the glomerulus. Um we have arteriosclerosis and ischemia to the glomerulus as well which causes injury. The glomeru has there's a high pressure of blood going through it, um which also causes damage and also hyperfiltration like we saw in uh and diabetes and then due to the progressive damage, the kidneys trying to compensate for the high pressure. So it's making more ex extracellular matrix and the the glomeris is becoming quite sclerotic. And then this is a kind of cycle of damage where we have reduced nephron numbers because of this um which leads to worse hypertension and then once again, worse, uh more nephrons are being lost. So, yeah, these changes result in a reduced G fr and therefore progression to chronic kidney disease. Ok. Yeah. Just uh remember guys, you can ask me questions at any point. Um OK. The next, the next SBA which feature would you see on renal biopsy of diabetic kidney disease, uh diabetic uh chronic kidney disease. So, Chemel Steel Wilson nodules, amyloid deposits, subepithelial humps, glomerular crescent and linear IgG deposits. I'll give you guys a minute or two for this. OK. Five more seconds. OK. So the answer was Kimmel Steel Wilson nodules. OK. Good. So that was the, the majority. But don't, don't worry if you didn't get it. Ok. So the reason why we get these is there's a, like we mentioned before, there's a high pressure uh that causes the mesangial cells to create uh to create more extracellular matrix which leads to the glomeru actually becoming larger. So these nodules you can see. So this is an example of a renal biopsy for someone who uh with diabetic chronic kidney disease. And if you look here, this is the glomerulus. If you look here and here you can see there's a kind of, it doesn't look like cells, it's actually extracellular matrix, um which is being secreted by mesangial cells to kind of compensate to the high pressure. So those are the Kimmel Steel W Wilson nodules. Uh Once again, this is a really important er fact for exams. OK. So what investigations do we do in chronic kidney disease? You can put it in the chart if you know, OK, it's OK. If you don't Um ok, so the first thing is we wanna investigate protein in the urine. So how do we do this? Um, so we have something called the albumin creatinine ratio or ACR for sure. Um, there is also something called the, er PCR. So that's the um, so albumin creatinine ratio basically is how much albumin is in the urine, right? So if, if that's higher, it's worse because we shouldn't actually be having much albumin albumin in the urine because it's too big of a molecule to normally get filtered by the er, oh yeah, good. Someone put ACR. Yeah, good. Um, it's, yeah, it's too big of a molecule to actually get filtered by the kidneys normally. Ok. So, yeah, that we use the ACR, it's clinically important if it's, the HR is over three mg per miller. So that's an important number to be aware of. Oh yeah. Good. Yeah. So eg fr as well. Yeah, perfect. Um, how is the ACR sample collected? This is just a small factor you need to be aware of. So normally say if someone comes into primary care and then the GP orders uh, an ACR sample to be collected, they send them away with uh, like a urine, um, like sample bottle and then they have to go. So the first thing in the morning, the day after the first pass, that means the first bit of urine that comes, um, the first thing in the morning, that's what we collect because that allows us to get the best i idea of what the, how much albumin is actually in the urine. Ok? If the initial acr is between 3 mg, er three mg or yeah, 3 to 70. So you say you're in primary care, you sent them away, you've got the results back, it's between three and 70. Then you need to confirm that by doing a subsequent early morning sample. Ok? If it's above 70 then you don't need to do a repeat sample and then you can carry on with your, your other investigations. Yeah, fun. When do we need to refer to the renal doctors? So, if the ACR is above 70 we need to refer unless they're already being treated for chronic kidney disease or it's being caused by diabetes. We also need to refer if it's above 30 and there's persistent blood in the urine. So, hematuria is blood in the urine after we've excluded a uti um, two thirds. So persistent hematuria just means that if there's two thirds of the di two out of three dip dipstick tests show one plus or more blood, uh That's what we would count as persistent hematuria. Ok. And then you can consider a referral if it's between three and 29. Uh, and there's persistent hematuria as well as other risk factors such as cardiovascular disease or the EG FR is going down. No. Ok. So diagnosis, usually we, we diagnose using a clinical history and examination as well as with the, the stages of C KD. So we use EG Fr as well to diagnose um chronic kidney disease. Ok. So we said before that we use EG Fr and the way that we get eeg fr is by using uh serum creatinine. So that remember that's one of the molecules that is naturally broken down from muscles. Um and in the blood and it should be excreted by the kidneys. And if that's building up in the blood, that means there's something wrong. Um So yeah, we usually use serum creatinine. The most common way we work out. The eg fr from serum creatinine is using an equation. So that's called the modification of diet and renal disease. Uh You don't need to know too much about it, but you just need to be aware that the equation uses these variables. So serum creatinine as well as age, gender and ethnicity and you can just remember them because it spells sage. Um So that that's what is taken into account when we work out the eg fr using this equation. OK. So serum creatinine, remember at the beginning, we we mentioned that it's not always, it doesn't always provide the most accurate estimation um of the eeg fr and the reason for that is if there's differences in muscle, OK. So you need to remember there is an inverse relationship between serum creatinine and eg fr. So eg fr if it goes down. So that, that means the renal function is going down, it's not uh filtering as much blood as it should be per minute. That would mean that the creatinine which is in the blood and is normally filtered would be building up. So that would go up. Yeah. So as one goes up, the other goes down and vice versa. Ok. So now I'm gonna go through a couple of scenarios, um that allows us to apply this to try and understand what, why uh sometimes the EG fr isn't as reliable as it should be. So in pregnancy, we actually get a higher eg fr. So it, it looks like it's better than uh it actually is. Yeah. So it's an overestimation. The reason for this is because in pregnancy, the heart's pumping harder. So that means there's more blood flowing through the kidneys and therefore there's more excretion. Um So that really uh causes an an increased G fr. The next example is in amputees. So if the er because the equation only uh takes into account serum creatinine age, gender and ethnicity doesn't take into account how many uh how much muscle mass we have uh an amputee. If they're missing an arm or a leg, it means that doesn't uh it would, it would result in a lower serum creatinine just because they would be missing a few muscles um which results in an increased eg fr. So we're overestimating their kidney function just because we're seeing less creatinine. But that could just be because there's r they, they don't have as much muscle mass as we expect. OK? And then on the other hand, a bodybuilder would have a lower eg fr because there's high creatinine because of increased muscle mass. Uh And the last example is if we uh eat red meat right before the test, that's gonna also show a, a lower G fr than it. It actually is because of the creatinine that would be found in the, the meat. OK. The next SBA what is the gold standard test for glomerular filtration rate? So what is the, the best way to calculate the G fr give you a couple of minutes for this? 10 more seconds? OK. Good. OK. So the majority put the in inulin clearance test. OK. So the question said, what's the gold standard for glomerular filtration rate? Not the estimated glomerular filtration rate, which is why we would use the serum creatinine. Um The actual glomerular filtration rate. If we weren't gonna estimate it, we could work out using the inulin clearance test. So this just means in inulin is just a molecule that is normally it's 100% excreted by the kidneys. So if we measured that it's, it's, it's the ideal substrate to measure G fr. Um So yeah, that's just AAA nice fact to know. OK, let's talk about management of chronic kidney disease. So the general management uh in most of the patients would be to give them a statin. So for all chronic kidney disease patients, we wanna give them a statin for the prevention of cardiovascular disease. Because if you have C KD, it predisposes you to have uh cardiac issues, we also wanna consider giving ace inhibitors in certain scenarios. So if you have diabetes and your ACR is above three, then we would consider giving an ace inhibitor. If the patient had hypertension and the ACL was over 30 then we'd also consider giving ace inhibitor. And then we also give them for any patient who has an ACR over 70 regardless of if they have diabetes or not. Ok. The dietary advice, uh we, we, we, we should give is that we want them to be on a low protein diet just because we don't wanna kind of cause any stress onto the kidneys. Um and as well as low phosphate, low sodium and low potassium. So it's easy to remember cos everything is low. Um And then if they need it, we can consider, especially if in stage five, for example, stage five chronic kidney disease, we can consider renal replacement therapy. Um and this would be a whole tutorial in itself. So we don't have time to go into it as much, but just be aware, it encompasses hemodialysis. We and we saw the A V fistula earlier. So that's where this comes in peritoneal dialysis. So that's dialysis kind of through the the peritoneum and then uh renal transplant as well. Ok. So specifically, uh so the reason why chronic kidney disease management is a little bit tricky is because you need to think about each of the specific kind of causes as well as issues that may like come from it. So for example, hypertension in chronic kidney disease is managed with ace inhibitors first line. So like we said before, any patient with KD should be on an ace inhibitor. If their ACR is over 30 uh with hypertension, the way that ace inhibitors work, it's nice to just understand it where you can see this image again. Um they reduce the filtration pressure in the glomerulus by dilating the efferent arteriole. So if this, it kind of, I mean, you can imagine it as a as a hosepipe if we were to clamp down the efferent arteriole, that would cause a backup of blood here and the pressure would go up and that would cause everything to secrete. So we're doing the opposite, we're dilating this which would lower the pressure here um and put less stress on the, on each of them glome um which is good, which is a good thing cos it, it kind of helps to uh treat the hypertension. But we wouldn't actually see because there's a lower pressure here. Um a slight decrease in the G fr because the blood isn't getting filtered through as much. And therefore, if there's a decrease in G fr, we would see a rise in creatinine as well because they're in, in burse with each other. OK. Uh So we need to also make sure that we're not allowing either of those two things to rise off for too much once we've given the ace inhibitor. So these two numbers are very important to remember if we see a decrease in eg fr up to 25% after we've given the ace inhibitor, we need to stop it or if there's a rise in creatinine of up to 30% anything above that is, is not acceptable. Um And then we would stop it if it's risen uh up to like 20 20% the creatinine or it's decreased about like 15%. So it's still within the, the limit that we're allowing for. Um we would just kind of recheck the renal function two weeks after another reason you would stop the ace inhibitor. Uh is if the potassium was going up, would you use uh calcium channel blockers? So, in chronic kidney disease, you would use the, the ace inhibitor because that's treating the chronic kidney disease as well. But then if, if this doesn't work, then you would switch over to the calcium channel blocker. OK. Yeah. So yeah, for example, here we have um we would switch to another antihypertensive, not an uh anti tensor receptor blocker. OK. Uh The other medication we could give is uh furosemide as well. So, this is just a useful thing to know as an anti hypertensive uh especially when the G fr falls below 45. Ok. So the next thing is mineral bone disease and chronic kidney disease. Ok. So this is a very important kind of aspect of uh of this topic. So when you have chronic kidney disease, it results in the disruption of calcium and phosphate balance. The reason for that is the kidneys normally raise an enzyme called one alpha hydroxylase, uh which activates Vitamin D And when you activate Vitamin D in the body, it allows us to kind of absorb more calcium from our diet. But in chronic kidney disease, there's a reduced activation. Uh there's less sorry, there's less one alpha hydroxylase which results in reduced activation of Vitamin D which means we have hypocalcemia, we have less calcium in the blood. Um to compensate for this, the parathyroid gland is releasing more parathyroid hormone um which causes the bones to lose more calcium and that causes uh chronic kidney disease patients to have weak and brittle bones. So, there's an example of secondary hyperparathyroidism. Um All of this results in bone pain fractures and features of os of renal osteodystrophy. So we're gonna talk about that in a second. Um These are some examples of renal osteodystrophy. Give you a minute in the chat just to try and guess what any of these are. Oh, yeah. Wait, before I just wanna clarify, you can use uh angiotensin receptor blockers here. It doesn't just need to be ace inhibitors. Um But you would, you would still switch with the same criteria as, as we've mentioned before. OK? Any, any, any ideas give you 10 more seconds before we move on, just put it in the shot. OK. So the first one is uh rugged jazzy spine. So you can see there's an example there. Um It basically just means you can see that uh it goes from kind of lighter to darker and it alternates. So that's one example. Um you also get pepper pot skull and you can kind of see there's like lots of little dots of white um across the skull. So that's another example of mineral bone disease in chronic kidney disease. Um And then the last one is uh if you see here, I appreciate it's a little bit hard to, to see, but there are some lytic lesions in the hands. Uh It doesn't necessarily need to be in the hands, but you can see lytic lesions. Uh So those are called brown's tumors. Um So these, you would also see these in secondary hyperparathyroidism. So that's the same thing as mineral bone disease in KD. OK. So how do we manage it? The aim of our management is to reduce phosphate levels and also reduce parathyroid hormone levels. So how do we do it first is lifestyle? So we wanna reduce dietary intake of phosphate if that doesn't work we can give phosphate binders so we can give calcium based binders. Um But then we also need to be aware if we're giving something that's got a lot of calcium in that might lead to hypercal hypercalcemia side effects. Um Sevelamer is another uh phosphate binder, but it's non calcium based and it just works by binding to the dietary phosphate and preventing it from being absorbed by our bodies. We can also give Vitamin D but we would give uh alfacalcidol because that, that basically means it's a, it's a type of Vitamin D that's already activated because in chronic kidney disease, we don't have one alpha hydroxylase to activate the Vitamin D So this kind of bypasses that and allows our patients to, to still get Vitamin D and then if none of these work, we can consider, you know, in severe cases of parathyroidectomy. So, removing the parathyroid gland. Ok. Uh The last bit uh is uh anemia in chronic dis er kidney disease. Ok. So, the reason why we get this is uh kidneys are normally responsible for producing erythropoietin or EP O. So, ep O is responsible for uh kind of promoting red blood cells synthesis. But in chronic kidney disease, the they're not producing enough EP O which results in low red blood cell levels and therefore anemia. Um additionally, because of the high urea levels in the blood, this also has a toxic effect on the bone marrows. Um And that also reduces erythropoesis. So this all leads to a normochromic normocytic anemia. So, normal color and normal cell size. So the M CV is gonna be normal. Um This usually becomes apparent when the EGF when the G FR is below 35. Um How does this result in a three fold increase in mortality in renal patients? Well, the reason why we're worried about this is because it can predispose to the development of left ventricular hypertrophy because the heart's trying to compensate for lower red blood cell levels by pumping more blood around the body. Um And then if it remodels, it can kind of lead to potentially like cardiac arrest or MRI S. OK. How do we manage this? We have a target hemoglobin of 10 to 12. Uh First thing you wanna do is always determine and optimize the patient's iron status. Um So this needs to be done before we uh give uh the medications. So, yeah, and then you would correct them if it, if they were low, for example. Uh and you can do that through ferrous sulfate or ferrous gluconate. And then some patients might even require IV iron infusions after we've optimized, er determined and optimized iron. Um then we can think about giving medications such as erythropoiesis, stimulating agents or E SAS. Um So, erythropoietin and gabapetin are examples. Um And yeah, you only give them once the iron is normal. OK. It was the last uh question for me what feature of end stage renal disease is shown below. So this is a blood film and you can see that there's some kind of interesting looking cells can put in the chat. We just take a guess. Give you a minute. Any ideas. OK. So this is a bur cell or an EK inocyte. Uh This is just something I just throw in just so you're aware of it. But yeah, the these basically come about when you have high level of urea in the blood. Um So it might be quite a, I don't know, it would be a bit unfair to ask you this in the exam but maybe they, they would. So I just wanted to show you. Ok. Uh One last slide from me is just quickly, how would you, how would you differentiate AK I so acute kidney injury from chronic kidney disease. So on renal ultrasound, chronic kidney disease usually has bilateral small kidneys. So if they, if they say that in the question, um that means that they uh oh sorry, I just saw, saw someone types. Yeah. So yeah, they, they were, they were burst cells. Um Yeah, so sorry. A as I was saying that you'd normally see bilateral small kidneys except if you have C KD with any of these um ADP K DS, autosomal dominant polycystic kidney disease, diabetic, nephropathy, amyloidosis or HIV associated nephropathy. Um and some other features that suggest chronic kidney coronary kidney disease, over an AK I would be hypocalcemia anemia and high phosphate levels. Yeah. So the bur cells, uh sorry, let me just go back quickly. So the bur cells come from high levels of urea in the blood, that kind of messes up the membranes of the red blood cell and causes them to have those kind of spiky that spikey appearance. Ok. Cool. Ok. So the next, uh I'm gonna hand over to DEA to talk to you a bit about nephrotic and nephritic syndromes. Ok. Great. Um So I'll send the feedback form at the end as well. Um So if you guys could fill that, that's really useful for us. And we're just gonna start uh talking about some um nephrotic and nephritic syndromes. So, the first thing I'm gonna do is talk about the glomerulus and Bowman's capsule. I've already introduced it and I'm sure you uh some of you already know about it from your preclinical years. So, on the left, we have the gray area which is showing the Bowman's capsule and inside it, you can see the lumen of the capillaries. Um And so I wanna talk about a few key bits. So these purple, um not these purple, sorry green cells are mesangial cells and these are essentially structural cells which help support the glomerulus. Um And on the right, I have a diagram just showing the layers that um a substance has to be filtered through. So at the bottom, you've got the lumen of the capillary and the endothelium on top of that followed by the glomerular basement membrane. And then we've got the podocytes, these are the foot processes of the podocytes. Um And then after that, the bowman's capsule. So at the bottom here, I've got a couple of spaces that will be important when we start talking about some of the nephrotic and nephritic syndromes. So, subepithelial space means um between the podocytes um and the glomerular basement membrane. So if I call, you could just hover around there. Uh on the right diagram, please. Um OK. And then subendothelial means between the glomerular basement membrane and the endothelium of the capillaries. And then mesangial space is something that's within the mesangial cells. Um So we'll talk about the, these, these time, this terminology will come up soon. So, if you could move on. OK. So we're gonna start to talk about nephrotic syndrome. Can anyone on the? Oh, well, I think I've already got it up. Um OK. Uh Can anyone on the chat tell me some of the main features of nephrotic syndrome? OK. Um That's fine if you can move on echo. So I've got and keep going. So I've got a um a Pneumonic OK. Great generalized pitting edema. That's great. So that's, so I've got a um uh the A Pneumonic pale. Um So it's a tetra of proteinuria, hypo albuminemia, hyperlipidemia and edema. So that's, that's the way that I would remember it. Um And if we carry on. Ok. So in nephrotic syndrome, typically, podocytes are damaged. Um and podocytes are normally negatively charged, they stop other negatively charged proteins from getting through. And because uh nephrotic syndrome affects the podocytes, this is why you get this massive protein urea. Now, can any. Uh so uh I'll talk a little bit about the complications that happen with nephrotic syndrome. So, the first thing is that you are at higher risks of uh uh V TSI. So you have lots of proteins that are involving the clotting cascade like antithrombin protein C and plasminogen. And because these are filtered through now, um because of the damaged podocytes, you have a higher risk of venous thromboembolisms. So, next, we have hyperlipidemia. So, because these proteins are getting through the liver tries to compensate this loss by increasing the lipid production to maintain our osmotic pressure. We have an infection risk as well because antibodies are lost. Um and it has a risk of chronic kidney disease. So, the general management is that we advise a low salt diet just to um a, a higher salt diet would worsen the fluid retention. And uh so that you can get given BT prophylaxis and furosemide to help improve the edema. So, now we're gonna talk about some specific um uh uh nephrotic syndrome. So, I've got my first SBA um and I'll put the pole up now. OK. So I'll give you guys a few minutes to have a read of that. It's quite a long question. Ok, great. We've got some responses coming through anyone that's responded. Um If they wanna type in the chat, what type of nephrotic syndrome? They think it could be. Ok. So if we move on. Um, so the type of nephrotic syndrome was glomerulus glo uh no, membranous glomerulonephritis or membranous um nephropathy. Um And so on the second picture, I've got a picture of a normal uh glomerular filtration membrane. And you can see it's fairly thin and you can see the podocytes quite clearly. And on top um the electron microscopy shows a thickened glomerular um membrane. And it's got these the spike and dome appearance because of deposition of um uh antibodies. So, if we go on to the next slide, OK. So me glomerulonephritis is the most common type of nephrotic syndrome in adults. And the third most common cause of endstage renal failure. So, essentially what happens is that antibodies, the P two R antibodies, they um ha uh they create im immu an immune response to the basement membrane and essentially form clumps around the subepithelial layer. So, if we remember that what uh uh that the what the sub epithelial layer was, it's between the podocytes and the basement membrane. Ok. Um And in terms of the causes, um it can be mainly idiopathic um but malignancy is also a big cause about 5 to 20% are caused by malignancy. Um So you might uh they, if a patient presents with this, it's uh you can do a CT um to see if there's a malignant cause some drugs like uh gold pencil lamine and nsaids and also se can cause it. In terms of management, all patients should receive an ace inhibitor or an ab um if they can't take an ace inhibitor to reduce the proteinuria um and immunosuppression. Um if this, the patient has a severe disease, um and you need to treat any secondary causes um like sla for example, or malignancy in terms of prognosis. Um So the rule of thirds means that a third of patients tend to have spontaneous remission. Um A third of patients remain proteinuric and one third unfortunately develop endstage renal failure. OK. So if we move on, we've got another SBA. Um So I'll put the pole up, please keep putting any questions on the chart if that wasn't clear. Ok. OK. Great. We've got everyone saying it's FSG S. So if we go on to the next slide, so we've got some key words here that tell that, tell us there's FSGS. So IV drug user um and we'll go on to why that is in a bit. And then the light microscopy showing focal and segmental sclerosis of some glomeruli. So that is um the histological findings. So if we go on to the next, so, focal segmental glomerulosclerosis is when there is glomerular injury to a specific area of podocytes. Um So now sometimes this might, this might look like a bit like the Kimmel Stone Wilson, no nodules, but the history will tell you a little bit more about it. Um So, like I said on renal biopsy, you have this focal sclerosis and you can see it in the picture and you'll also have effacement of foot processes on electron microscopy, uh which is essentially they look fused together, they don't look nice and separate um like on the normal one. A classic SBA sign is a patient with HIV or a heroin user. Um Now I didn't make it clear that it was a heroin user, but that was just um in there on top of the um microscopy findings to help you. So the the cause is again, it can be idiopathic, it can be secondary to another renal pathology. Um HIV heroin use and sickle cell, for example. Um And the management is steroids and immunosuppression. Um And unfortunately, even after transplant um in endstage renal disease, um there's a high rate of recurrence of the sclerosis um for these patients. Um OK, let's move on. Um I'll put the next pole on. OK, great. Everyone's decided on minimal change disease, which is perfect. OK. So now I have a slide um on minimal change disease. At the top. In the picture, you can see the normal foot processes of the podocytes. And if you look at the picture below it. That is showing minimal change disease in electron microscopy. Well, these foot processes are fused together. Um So this is the most common nephrotic syndrome in Children. So usually um if it is signs of nephrotic syndrome and it's in a child, that would probably be the answer. Does anyone know why it's called minimal change disease? You can type on the chat or unmute. Ok. I can just tell you. So um on light micros, oh there's no change. Perfect. So almost there's no changes on light microscopy. And yeah, in on electron microscopy, there are changes. Um you can see some of the effacement of the foot process blis but yeah, mainly the the lack of changes on light microscopy. Great. So I've got the key phrase that they like to describe the electron microscopy, which is podocyte fusion and effacement of the foot processes. Um And in terms of risk factors, uh the main ones are some drugs like um nsaids and Rifampicin. Hodgkin's lymphoma um is a is linked. Uh it's linked to that and then also infectious mononucleosis. So it's in terms of its treatment, most of them are steroid responsive and this very rarely will turn into chronic kidney disease and cause endstage kidney failure. Um If it is not responsive to steroid, you can move on to cyclophosphamide. Um And yeah, so like it says, uh it rarely progresses onto CKD, move on. OK. So now we're gonna talk about a little bit about nephritic syndrome. So, the difference between nephritic and nephrotic is nephritic syndrome, affects the blood vessels and red blood cells leak. And that's why you can see hematuria, hematuria might be microscopic or mi microscopic um or both. Um and there are red cell costs can, that can be seen in the urine. There'll be protein loss but um usually less than in nephrotic and uh there'll be sterile pyura, um hypertension and urea. So, in terms of why these things occur, so there is inflammation that causes injury to the glomerulus. And this activates complement leucocyte recruitment and free radical productions and the injury to the glomerular membrane. Um and sorry and the basal membrane causes proteinuria. Um inflammation will also affect the uh glomerular capillaries. So the red blood cells will leak because of this inflammation, white blood cells are recruited, but there is no bug. So that's what causes the sterile pyura and then rash, which is the r angiotensin um system is activated. And this, so because of the glomerular damage, there's less geo form which causes more redden to be released from the kidneys which causes hypertension. Ok. And the le the the reduced G fr is why there's oliguria as well. So you've got a question on nephrotic syndrome. Um Wait, I will pop now. Ok, great. So everyone has the iga nephropathy, which is correct. So this is uh this picture is showing immunofluorescence, which is the likely picture if they are talking about ig it's unlikely they'll give you electron microscopy or light microscopy will probably be a picture like this showing these iga deposition in the mesangium. So if we move on, so iga nephropathy is also called Buerger's disease. And it's one of the commonest causes of uh glomerulonephritis worldwide. So, the typical patient is a young um young patient um who comes with macroscopic hematuria and this will usually be uh followed by, followed by an upper respiratory tract infection uh a day or two ago. So the IG ig a complexes deposit in the mesangial cells which if you remember the structural cells of the glomeratus um and renal biopsy like I showed you in the picture is positive for immunofluorescence similar to the other um managements. We have ace inhibitors and steroids if um they fail to respond to ace inhibitors. OK. So we've got another question now. OK. OK. Great. So most of you have got this right. Don't worry if you don't. It's this is a hard one. So this is rapidly progressive glomerulonephritis. Um So the key word in this was the CRE crescent formation and over 50% of the glomeruli. Um And I know it's a bit difficult to see, but we've got um an arrow pointing to this cresentic shaped scar that occurs in the glomerulus. So if we move on so rapidly progressive, uh glomerular nephritis is a term used to describe when there is a rapid loss of renal function of over 50% within three months. So, the main causes are s good pasture syndrome, microscopic polyangiitis. Um and uh Wegner's granulomatosis. Um so they have Nephritic syndrome features and then also specific features, for example, in good pastures, they'll also present with hemoptysis or um Wegner's will also um present with sinusitis. So they'll have the specific um symptoms of the, of each of the conditions as well. Um You can see that there is the uh crescent shape scarring, uh which is the keyword for exams. Um Yeah, so if we move on, so essentially, we've not managed to cover in the time all of the intrarenal conditions, but here is a nice summary of them. And if you move on, I've got a list of particular intrarenal diseases we didn't cover today. Um So we went through a lot of the high yield ones that tend to come up in exams. Um And these, hopefully you can cover in your own time. So thank you very much for watching. Um I'm gonna send the feedback form. Um please please fill it out. It's really helpful for us um to improve our next tutorials as well. So, and thank you very much for watching. Ok, thank you. Thank you guys for coming. Yeah. So, uh I think you just need to provide, once you provide the feedback form, the slides will be on the page