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Good evening, Rizwan. Hi. How are you? Good, good, good. So, uh yeah, we'll start kicking off. Let's give it a minute or two. So, uh Good evening, everyone. My name Is she here? I'm the co founder of the six PM series. Uh, we're very delighted to have, uh, Doctor Rizwan in with her today is going to talk to us about renal medicine. Um, and we're very happy to just restart again. Uh, for those of you that may not have heard about us during the pandemic, we, uh, did quite a few lectures for clinical year medical students. Uh, they were all done by junior doctors, and our aim was to try and bridge the gap in clinical education that may have happened during the pandemic. We have continued past that point, and since then we've talked about, uh, 30,000 attendees, probably more than that, much more than that now. And we've got quite a bit of feedback. So if you or anyone you know is interested in teaching or is interested in education or research around education, we have a lot of data. We have a great platform and infrastructure. Um, and we would love to get involved with anything that you'd have to offer. So drop us a message on the six. PM series, whether that's our instagram page or our Facebook page. Uh, and we will we will get back in touch with you. I think that's all I really have to say. Uh, there's one. Please feel free to do any introductions. And, uh, any kind of background that you want to talk about and the lectures. All yours. I'm gonna move offstage. I'm just going to check that we have nema here as well for troubleshooting. She's okay. Um, the other thing. I will tell everyone that if you're not familiar with the metal, uh, platform, it's actually brilliant. We've been using metal for quite a while. We've recently started using all of our, uh, teaching completely on metal. So we've moved away from Zoom. Um, I'll show you a couple of things here. The feedback will appear at the end. You can see it in the chat. We will send it out. There are some polls that were released throughout the lecture, and they should correspond with what's on the screen. You can talk to us through the chat. Um and I think that's everything. Our goal from now forward is to try and have a recording available of all of the events so everyone can view it on cash up that will be available on our page and metal as well. Uh, that's it. Thank you so much for coming. And, uh, doctor was one element over to you. Thanks very much. You're here for the kind introduction. Um, so hello again to everyone. Uh, my name is Rizwan. I'm a doctor. Um, I work in Dublin in the public of Ireland. I'm working in an acute medical assessment unit at the moment. Um um and I'm f y two. Great. According to the UK. So I was asked to just give this talk on renal medicine. Um, so I've prepared this for you guys. Um, so just two before I start, um, just I think everyone realizes that clinical nephrology can be quite difficult. And the reason I think everyone, including myself, you find it so difficult is that there's more than anything. There's a lot of tie into your basic sciences your your biochem, your pharmacology or physiology. Um, but I think clinically speaking day to day it's not so important to know every single detail, you know, it's not always so important to know why it specifically the mechanism of what something happened or why it happened. Usually it's enough to know that it does happen. For example, the side effect of a medication we prescribe, Um, keeping that in mind, Um, you know, there are some high yield topics in nephrology that I feel get tested, um, commonly and show update today. So we're going to go through them today. Um, and despite my best efforts, I won't be able to cover everything tonight. Um, so just use this talk as a way to kind of recap the basic, the major concepts. Um, and we can test ourselves at the end as well. Um, and if you have any questions, then maybe you can keep a note of them, and I'll try to get to them at the end. So the talk today, it's going to be roughly just over an hour. Um, firstly, we'll go through some basic anatomy and physiology. We won't be doing anything too in depth, but just the clinical aspects and what's relevant to us clinically. Um, then we'll go through some renal pathology, some diseases, and then we'll go through some clinical cases. Um, there's a couple of things I won't be covering. I feel because they'll be covered elsewhere. Clinical by clinical biochemistry and kidney stones sometimes are covered by by the urology doctors, the surgeons. So, yeah, I know nephrology isn't always the most, uh, enthralling topic, but sure, look, that's what we're here. Let's try and get through it. So just one slide Embryology again only been mentioning it because of how it presents with the disease state to us clinically with our patient's. So the kidneys. The renal system develops from the mesoderm in embryology. Um, the urinary Qubad as you can see the thing and yellow here connects onto the mesonephric, uh, metanephric mesenchyme. And this interaction is what allows the development of of the the kidneys and the collecting system. And there's whenever there's a problem with this interaction, that's when you start to get, um, pathology. So if there's an incomplete interaction, you can get informed. You know, kidneys that are informed very well, so multicystic dysplastic kidneys. And if there's no interaction, for whatever reason, you can get completely genesis of the kidney. If a single kidneys affected in this state, then you know the other kidney. You know, hypertrophy ease and compensates. Um, if both kidneys are gone, then you can get something called Potter sequence, which I'm sure you guys are aware of. Um, in usual. Um, the amniotic fluid is produced by the fetus kidneys. So if there's no kidneys, there's no amniotic fluid. There's nothing to protect the baby in the womb. So you get this, um, you know, limb deformities, flat face and and long type of glacier as well. Um, then just a few other things that tie into embryology, I'll go through step by step. So the first one is Wilms tumor. So it's type of renal cancer that commonly affects Children, the most common type that you see in young Children. And it's relevant because the actual tissue that we see that proliferates is that metanephric mesenchyme or blastema that forms in the neurological tissue. You see that, um, in young Children, which obviously you shouldn't see, um, then there is the, you know, your your your tear a pelvic junction obstruction. So, um, commonly, you see that at the junction of the pelvis and the ureter. Um, you can get stricturing in utero and can cause hydronephrosis iss. Um, basically, do two malformation of these dots, and they can cause pathology. You can have duplex collecting system, so save this. Um, if the you're tracked brought when it comes into the kidney, it bifurcates. You can end up with two ureters, and it's important because it can result in the next condition, called the cycle uteral reflux. Um, so it's a really common in Children that can cause recurrent UTIs can be primary when those specific houses secondary secondary to do to some other pathology anatomy. You can have remnants of the urachal duct, so your ankle doc connects the bladder to the umbilicus Unusual. If there's remnants are in complete obliteration, you can get remnants and they can cause problems down the line. And then you can get horseshoe kidney as well. So that's just the duplex ureters. Um, that's the urachal remnants, and then this is the horseshoe kidney. So this is when the inferior post of the kidneys a fuse. Why it's relevant is that you may see this or pick this up. Incidentally, on a CT scan, an MRI scan. Um, and you worry about you, you know, wonder about the significance, the thing to keep a notice that it can be present in syndromes, down syndrome, Turner syndrome. And it can also lead to the cycle uteral reflux as a result of abnormal ureters. So let's get to the anatomy. Um, so our kidneys lie in the retroperitoneum. Um, and the spinal level is usually from the T 12 down to L3, um, the average size, about 10 to 13 centimeters, and that's relevant. When you're reading auto sound reports or any kind of imaging, you should know how how big a kidney is meant to be. Um, it's applied by easily named the Renal artery and vein, Um, and it takes a lot of the cardiac output per minute. So about 25% to try and clear clear through all that, all that blood. So it's one and done abdominal thing to be aware of is the way the left testicular vein drains into the left renal vein. Um, this is important because it results in, you know, less than ideal blood flow. At times, it can cause a varicocele on the left side. um you guys will remember that the right testicular vein drains directly into the IBC. Um, then sometimes I think on exam on a clinical exams and finals, you make it asked to differentiate. Or how do you differentiate a spleen versus a palpable kidney? An example? Um, I know I was asked that before and just a few points to remember that its location doesn't move with respiration. Can you get above and things like that. Um, so for the coming in kind of closer, um, the functional unit of the kidneys, the nephron. Um, we have about a million of them per kidney. Um, the way they're range can result in result in an outer region called the cortex, and an inner region called them a dollar, which you can see in the image there. Um and then the nephron can be further classified into the vascular component and the tuber component. So here's a kind of funny looking drawing, but what you can see there is in the red. That's the the art arterial supply. So initially comes off as the the Afrin arterial with a for arriving arrives into the glomerulus divides into the glamorous, which is a tuft of capillaries and then exits as the different arterial. That's all part of the vascular supply. And then the tubular part of the nephron is this Bowman's capsule, which leads around to all the different collecting system and then eventually to the collecting duct. So let's start by looking through the primary list the vascular section first. So this is really the you know, the where all the business happens in the kidney. Um, it's special in that it's one of the only places in the body where the capillaries don't turn into venues after they've been. You know, the blood flows through them. It exits as another arterial. And the reason for this is that we have tight control of both arterials so we can closely monitor and change. How are G f r, you know, effects, then the reason this is relevant as well, clinically is that the the effect of drugs on these arterials. So prostate London's, um, dilate the different arterial so increased blood flow to the memory list. Um, we all know the insets can block pressure gland in Axion and production, and as a result, they can cause constriction and reduction in renal blood flow or plasma flow. And this is one of the mechanisms by which, you know, giving someone an NSAID may cause some reduction in the renal renal function. Then you have the exiting arterial which is acted upon by angiotensin two. So I'll get onto it by angiotensin two is a generalized vasoconstrictor. But it preferentially constricts the different arterial first or more than the Afrin arterial. So if you block it with an ace inhibitor, you can you know the net effect will be a reduction in flow across across the the glomerulus through reduced pressure. This is especially important if in the Clinton scenario you have someone middle aged man, uh, hypertension. Um, you don't really work them up. You start them on an ACE inhibitor, and they go into renal failure. That can be due to unmasking of a renal artery stenosis. So if if the blood flow coming into the glamorous is already reduced and then you're increasing the blood flow out, you really drop pressure drastically. And this is how sometimes Ace and neighbors can unmask renal artery stenosis. So what's the function? Um, it filters your plasma into bone and space as an altar filtrate. And these are the, you know, things. You can see that come out of it. Um, and it stops the filtration of most proteins and your your components of your blood, like white blood cells and white blood cells. So pathology happens when any of this is broken down. And what happens then is that you get leakage of protein leakage of blood into the urine, and that comes out as protein your hematuria. And importantly, it's him a trea with the red blood cell casts, which is different from him. A trea, which you may see further down in the urine urine tract. Um, I suppose the key site is that wherever whichever part of the glomerulus is affected by disease pathology, that's what ends up determining how the disease presents and whether it's a nephritic on a frolic pattern, and we'll get into that. So this is what I'm talking about. So here is the actual filtration bed, Um, kind of like to save what filters out everything. Um, yeah, no problem. Um, so the first step is this end of the, um So if you can see here, the red part is the blood. And then the yellow part is where the urine drains out into the collection system. Um, so the first barrier is this capillary and the theory, Um, so this is the walls of the capillaries. They're relatively, you know, large holes fenestrated. So large stuff can get through, but not large enough so that the red blood cells and the white cells and the platelets get through. So that's the first barrier. The next is the basement membrane, which is connective tissue type four collagen, which has a negative charge and that forms to repel things like albumin, which are also regularly charge. And then the last barrier to defense is your epithelium or your POTUS sites. Um, again, they have very small slits, and the form is a. The work is a physical barrier to stop anything else getting through. And then, like I said, you can get pathology at any one of these three places, and then whatever you, whatever is affected that results in either blood or protein or both coming through into the urine, and that's what we can detect. So how do we assess kidney function? It's a good, you know, We talk about pathology. But how do we actually assess when the kidneys are going wrong? Um, it's the familiar glomerular filtration rate is the actual unit we use now. If we wanted to measure it perfectly in a kind of, you know, ideal situation or lab situation, you use it. A chemical called insulin and insulin is perfect for this because all of it is excreted, Um, and none of it is re absorbed. All of it is filtered, but none of it is reabsorbed or secreted, which means that whatever goes through the glomerulus, you know it's coming out into the urine. So if you measure the clearance, you can calculate the filtration rate. However, we don't use this in practice. You know that we don't measure give an indolent to everyone we see. We use the closest, naturally occurring substance, which is creatinine, and you probably heard of this. It's a breakdown of Muslim metabolism, so it's not as perfect. A small amount of it does get secreted back. So there is some overestimation, but for the, you know, clinical, you know, work. It's it's perfect again. If we wanted to do it perfectly and by the book, we need to get multiple measurements, like plasma urine. Um, things like that. But practically this is, you know, not possible. So we use surrogate equations to try and get an impression of what? The granting clearances. So I have a question here. Why don't we use inulin? Um, I suppose that, you know, it would be quite cumbersome. We could give England to everyone. I suppose the cost is part of it, but, you know, as part of a renal profile, we already our body already creates a substance called creatinine. So once something's already there, that is almost as good. Then we just use whatever is there instead of using England, England only ever used in in in, like, physiology and love kind of experiments and then the last cabinet at the very bottom. It's, um, kind of a master is that you make it as an M T Q that if you want to assess Arenal plasma flow a nautical Amillia filtration rate, you can use this molecule called power and you know, hippuric acid or pH. So there's a subtle difference between G f r and plasma flow. G F four is whatever it gets filtered through the glomerulus, but plasma flow is that plus whatever gets whatever flows through the capillaries, so there's a minor difference. But just remember, P. H uh, and then I'm sure you've heard of the equations that we use. So this MDRD but the more commonly used one in practices the Cockcroft golf equation. Um, it's good if you can remember it. But just so you know, everyone has a calculator on the phone that they use day today. Um, it takes into account the patient's age, their weight, their gender as well. Um, so when we know GF four what? What? We can go back and say If it's something that affects it, you know what what kind affected your for and how we function. So there's usually there's two main theoretical forces, hydrostatic and oncotic. Pressure is it's like the same as competitors anywhere else in the body. You know, hydrostatic based on how much water and pressure is in the system and opposing the system. And oncotic pressure is the the presence of proteins in or outside of the vessel, and these two actions oppose each other. Um, good thing to remember is that we know that hydrostatic and chaotic pressures can change idea far, but on a day to day would be really impractical. If any time are BP drops, we can get up. You know our our G f r drops as well. That would be impractical. So our body is sort of a way to, you know, kind of get around this, and it's called auto regulation. So over a range of blood pressures are glomerular Filtration rate remains the same. How does it do this? There's a couple of ways so the arteries themselves, you know, respond to their own stretch and either constrict or dilate. And then also, the more important one is called the Tube. It'll glomerular feedback, so I'll show you in a second. I had a picture. Everybody see, it's it's covered the juxtaglomerular apparatus. So this is a very specialized kind of endocrine area in the in the kidney in the nephron, which response to certain stimuli and cause, you know subsequent effect. So one of that is a response to the detection of soda employed in the Europe. So if the glomerular filtration rate is reduced, then what you have is less urine being produced, less sodium chloride being produced into the urine. This is detected by certain cells. Um, and then what they do is they release either endothelin already kind in to try and increase or decrease that blood flow. It's a really sensitive way to make sure that our kidneys are working as they should. So, um, you can see here at this this graph on the right, you can see that over a wide range. About like 80 to 200 or systolic BP R G F R is the same now. That's not to say it will work all the time. It can be overwhelmed if there's a you know, perceptual or significant drop in your BP, and that's when you start to get to trouble with pre renal failure. So we talked about the vascular system, the memory list. You know the capillaries. Now let's talk about the tubular system, the other part of the nephron. So the ultra filtrate comes into the Bowman's capsule, which is what you can see here. It's the first part of the tubular system. Now, if you're thinking about this, if someone was thinking about it, they may say that, Okay, why can't we just filter everything we need to and keep everything we need to at the glomerulus initially and then just let everything out into the urine. We The reason we don't do that is because our current system allows us for increase in control and and tight control. So this ultra filtrate let's go more than what we'd like to. And then we selectively take back what we need to base in our physiological, um, you know, state at present. And that's done by the tubular system. So at different levels around the left, along the nephron, different things get taken back to different amounts. Essentially, what that means is that we contribute. There's tight homeostasis of water and electrolytes. It's important to note that the metformin at the bottom just conceptually that if you want to find out the excretion, total excretion of any substance, it is how much comes out through the glimmering list. How much is filtered, then you minus how much we reabsorb later on, and then add on how much we secrete as well. So that's essentially how you find out how much stuff electrolytes were clearing out. So again, why is it important to know this clinically, you know, this is a clinical teaching, Um, because there are some diseases that affect specific different parts of the nephron. And if you know how the nephron functions and it helps you understand how the disease presents itself as well as that, it's a key area for drugs. They target different receptors along there. Let's go through a few of these things. Now again, I'm not going to go into the nitty gritty. I don't think it's relevant, but let's talk about the key things that we should know. So starting, starting with the first part, the proximal tibial. So as I've mentioned when we filter through the glomerulus that we'd let go of a lot more than we'd actually like to let go, and then most of it is re absorbed straight away at this proximal tibial. So 100% of regular cose and amino acids are reabsorbed at this point, and 67% of our water potassium bicarbonate like that now by us knowing that 100% of glucose and amino acids as re absorbed, that should let us know. Or we should be thinking that if glucose or amino acids ever show up in the urine. It's usually a pathological state. The caveat to that is in pregnant ladies, and you can have glucose, and that can be normal. But other than that, it's abnormal, clinically relevant because of Fanconi syndrome. So this is a disease which results in kind of complete loss of proximal tubular function. It can be, um, congenital or acquired, for example, multiple myeloma or lead poisoning. And it causes exactly the opposite of what the tubal wants to do. So it causes glucose to be excreted in the urine. I mean, our assets, it causes loss of water. You know, hypertension. These are things hypochelemia. So if you know what the approximate tubal does, you know exactly what happens in Fanconi syndrome, then acid base balance as well. This is one of the key things that the kidney does, and a lot of it is done by a resort shin of bicarbonate. As you know, that acid base balance is dependent on protons and bicarb, mainly in the body. And when we metabolize day to day, you know our living our function that we make a net, um, production of acids. So we need bicarb to buffer that out, and this is done by resumption in the kidney. And somewhat we make as well, um, then coming on two drugs and there's a couple of drugs that act on the proximal tibial. One of them is carbonic anhydrase inhibitors. So you see the screen molecule here, they inhibit that and they cause, um uh, reduction in the absorption of sodium so more of it gets excreted, so you act as a weak diuretic and then importantly, SGLT two transporter inhibitors. So these are the new kids on the block, you know, topical flows and things like that. Um so they're used for heart failure and diabetes. Both, um, and the way the act is on the sodium glucose co transporter in the proxy materials. When you block that, where you get is sodium, more sodium, being excreted and more glucose. So it works well for both heart failure and and diabetes. Now, against side effects, you can think more glucose in the urine. One's more infections, and also the the significant one is, um, you glycemic DK. Then coming onto the loop of Henle again, we don't need to go into the nitty gritty, just big, big picture stuff. So the main function of the thin the whole loop of Henley, is to concentrate urine and reabsorb water. That's what the thin descending limb does and the ascending limb, Um, reabsorb some of that sodium chloride as well. It's relevant because loop diuretics act on the ascending limb, the sodium potassium to see oh chloride transposed transporter um, the loop relics. They work here, then coming on to the distal to wheel again. Only big picture stuff, usually physiologically a resort sodium chloride. And we can stop this by giving people thiazide diuretics. So this results in reduced sodium unemployed, uh, in the body and executed in the urine. And this is also where BTH can act and exert its effect on the kidney. Finally, the collecting doctor. So this is where kind of the tubular system ends, and this is where a lot of the Axion happens. So this is mainly where a lot of the salt and water is re absorbed into the body. If it's needed to be, and in exchange for this, we usually secrete out potassium and hydrogen ions. Now this is relevant because of two hormones. One is a th or anti diuretic hormone produced in the posterior pituitary. And it's produced in response to hyperosmolality, or serum. Basically, when we become dehydrated, essentially, you can think of it in a way or volume loss. Um, what it does and net you no result of it is that it promotes water retention. So we just keep in the sodium we keep in the water. Um, and it does this by aquaporin channels. The other major one is aldosterone, which acts here, Um, so it's a steroid hormone. And again it's released in response to, um, under Tencent. So the wrath system, when her volume gets low, it can be released by high potassium or a C T H. And then that effect, again like a D h, is to retain that water to increase our circulating volume. And as a result, it secretes out potassium and hydrogen. Um, this is relevant because of medications like aldosterone antagonist and also clinical pictures. Like, um, um, I'm not forgetting the name, but aldosterone when you have low production of aldosterone, um, then you can have a similar effects as if you're taking a diuretic. Um, okay, so one thing to go through now, when we're talking about physiology. Specifically is the functions of the kidney. So we've gone through some of them already. Um, but these are these six ones are kind of basic and easy to remember, and they're good to remember because their handy later on when we discuss about chronic kidney disease. So I always used to find it difficult to try and remember all the different, you know, causes or all the different, you know, presentations of CKD or the issues. The good way to remember is to go back, to think that what should the kid do and then in CKD, it loses all these functions. So usually it's very good at controlling our fluid balance. A different electrolytes asset base excretes nitrogenous waste project like urea, creatinine, ammonia, things like that. It produces, um, a restaurant rating for red blood cell production. And it kind of it activates vitamin D and plays a role in calcium regulation. So all of these are functions to the kidney that we should remember. So when we're talking about fluid balance and kind of maintaining, uh, effective circulating volume, the responsible system there is a raw system. So this is I always I've used this picture loads of times before. It's kind of a very good summary I feel of what it does, but in in essence, what the raw system aims to do or what it what it aims to do is to increase your effective circulating volume. It does this when understandably, when our volume is low or when it feels the volume to be low or perceives it to be low. It does this by barrel receptors in the Afrin arterial in the justice glomerular apparatus, Um, specifically the granular cells. So the first step in this is to release the rent in from the G A. Um this then goes on to activate angiotensinogen to angiotensin one. This then gets acted upon by a sin, the lungs, and it gets converted. The active form of angiotensin two, which is a real workhorse and causes all these effects, so increases the face of constriction releases aldosterone ADH um, also trying to increase the circulating volume. Um, the reason it's important is that clinically we target the system a lot in disease states like heart failure, liver failure, um, specifically with ace inhibitors to stop the production of Ace angiotensin two for ARB to stop the receptors at the distal end and also for the I say new, it's not the only more the heart failure drug psycho petrol along with valsartan entresto. So that works by reducing the breakdown of these natural peptide which opposed for us. So this is all kind of a gold mine for pharmacological um, intervention for these disease states. Um, then let's talk briefly about asset base. Now I won't go into detail again because I think clinical biochem could be a whole another talk. But it's so important in this that I thought I should touch upon it. So like I mentioned before, when we when we live, when we eat, when we work our daily day today we produce a net, um, you know, amount of assets over basis. So we need something to buffer this out or else we become too acidic and then we die. So the bicarbonate, our body, the base, our our body produces bicarbonate. It's a kidney's job to replenish this, um, so this is the kind of equilibrium equation in the body when it's deals with assets and basis, so you can see here's the hydrogen ions. You know what causes the acidosis? Here's the bicarb. Here's carbon tax on H 20. There's an intermediate I've left out here for simplicity. So if hydrogen, if you're in a state of acidosis or ankylosis a acidosis, the hydrogen ion is increased. Then you can use this equation to try and understand where the formula will shift, what will go up and what will go down. But if you just want to remember to keep it simple, if there is an acidosis, it has to be either driven by too much. CO two, which drives the formula this way or too little bicarb, which drives it the other way, drives it back up this way. So Alkalosis, then is either the exact opposite. So I think to make it simple, you know, if you don't want to go into the actual equation, just remember these two lines for your acid base. Balance is, um, it's relevant, obviously, because it's really easy. One to ask on the exams. They throw up a table with your with your A B G, and then they ask you to interpret it. Um, normally, it's It's not as simple as you know a simple acidosis. There's all usually, you know, two things that are abnormal. The P. This should be sorry. PCO two and bicarb will both be abnormal. One of them will be the cause and the driver and one of them will be a compensate Torrey response and you'll have to find out which is which. So here, the normal values. So again, like we discussed, the body has a buffering system, that respiratory buffering system and the renal buffering system. So as we know the carbon dioxide, too much of a result in an acidotic state so the body can get rid of it to induce an Alka Losis Or if the body is already in an alkalosis, they can try and retain that CO2 to bring the pH down. Similarly, the kidneys work by excreting, um, potassium, the hydrogen ions, and keeping in bicarb ions, or vice versa. So these are the two proffering systems in the body to maintain a solid B h. The important thing to note, I suppose, is that when you're talking about compensate Ori changes that will always move in the same direction as the offending agent. So what? I mean, by that is that, for example, if there's a respiratory acidosis because of too much CO2, the kidneys will compensate by also increasing the bicarb so the compensation will always move in the same way. If it's, you know, just a simple primary disorder. So, for example, we see here that someone's B H on an A B G is 7.29. So that's low. So we know that's an acidosis. Now I know from the previous slide, then acidosis can only be driven either by too much co two or two little bicarb. So which is it? So the CO2 is low, so it's not that those two little bicarb So this is a metabolic acidosis, and now I need to check if there's any compensation. Unlike I learned here, that compensation goes in the same way. So my CO2 is low, so my my bicarb is low. So my CO2 should also be low to compensate. And it is so then, you know, I would say that this is a metabolic acidosis with some respiratory compensation. Important thing to note when we get onto about mixed disorders is that the body is rarely able to completely correct to a normal BH with compensation if there's an ongoing disorder present. Also doses Oculus ISS. If you find that the patient's be age is normal, but they're PCO to undergo by carbs are abnormal, then you need to think about a mixed disorder before that. If we do find a metabolic acidosis, the next step is you're an Anca. So you'll all remember this equation. Um, you can either use this one or the one with potassium or without potassium. Um, I usually use the one without potassium. Just use whatever your your med school has taught you. Um, whatever you're used to, um, just know that the ranges differ slightly. It's important to calculate because then, you know, um, if it's a high anion gap, metabolic acidosis, ha GMA, then it has specific causes. If it's non benign gap, then there is more specific causes for that. Um, and then I was talking about mixed disorder. So that's this is something that always I found tricky stuff and tricky because it's not so intuitive. Um, like I said, if there is a normal ph and abnormal, you know, electrolytes, then you can think of it. Or sometimes if there's a metabolic disorder without respiratory response, which you would expect, then you can start to think of mixed disorders. But overall, I think you know it would be very unfair to give you guys these questions. Um, the only one that I can think of that you should probably keep in mind is aspirin overdose because it's so common that can cause a mixed disorder by an early respiratory alkalosis, because the the acid stimulates your medulla so you hyperventilate and then eventually the metabolic acidosis from the actual asset of aspirin being mixed in with your blood. The way you specifically detect these mixed disorders is like four or five different equations you can use. But again, you know, I would say that it's not so relevant here, so just know your basic stuff. Your approach would be to check for the B H to determine what it is, Then go to see what is the driver. Then check for compensation. And if you need, check the onion gap. That's asset base and here, the different causes. So, like I mentioned for your high anion gap in the measure, metabolic. Remember your pneumonic mud piles so I don't remember anything. But it's methanol. Your you know, uremia d k a. Um um so that can also include other, uh, acidosis as well. Like, uh, ketoacidosis to the starvation. Things like that as things like all salicylates, you know, you won't be expected. Remember everything, but just, you know the major stuff, then your non and Gap metabolic acidosis. So things like diarrhea, Addison's disease. That's all I can remember earlier spring lockdown IV saline, um, and R T A s, um then for metabolic alkalosis is usually hypochelemia. So it's important to note that potassium and hydrogen ions are inversely related in the body. If there's low potassium in the serum in the plasma, then your body tries to shift the intracellular potassium out to compensate for that and the way it does that it It shifts out one potassium for a hydrogen being shifted into a cell. So then low hydrogen in the body in the serum causes an arc yelos iss. So just know that potassium and hydrogen are inversely related. There's certain genetic syndromes that can be that can cause metabolic ax, calculosis, diuretic and severe vomiting and then respiratory acidosis. Calculosis are easy. It's usually due to hyper or hyperventilation and whichever causes both, so you can see them there. Um, okay, so let's get on to actual pathology. So what I'm going to cover today in terms of renal disease is is the following. So AKI Nephrotic person nephritic uti, a cystic disease, is cancers, rhabdo and CKD. So there's two aspects to covering kind of any pathology when their med school one of them is well be relevant under exams. And one of them well, like what's relevant for, you know, day to day on the wards and in clinical practice. So the things highlighted in bold is what I feel are kind of clinically relevant. You see them day to day. You know they're common, their bread and butter. It's important to know about them they can present in patient's as well. On the ward, the other ones are more. I feel testable on kind of written MCQ, these type of things it's still important to know about, but they're not relevant so much, Um, in the patient's you see day today, of course, different. If you're doing their volunteer rotation so Let's go through them anyway. I'm gonna start with a K I that I feel like one of the the most relevant things that, um, you should know students, because it's how common it is, how how often we see it. Um, so let's start with that. So how do we define an acute kidney injury? So there is a k d go glass, a classification. So this is a collaboration of the pathologist who come together to provide guidelines and definitions. So this one is really important to know. Recommend everyone to learn it. So it's any one of the three of those first three things so arise in your serum creatinine of greater than, um, 30.3 mg per deciliter within 48 hours. A rise of greater than 1.5 times your baseline that is known. Or you're you're involving to drop less than 0.5 mils per cake per hour. 46 hours. So you have any one of these three things, then you have an A k i. By definition, it can be graded on severity stage 123. That's more relevant. Um, in research and also, um, um you know, sometimes, if we want to compare people with a chi. Yes, it's very different. Someone has a mild versus severe, so it's important. Prognostically Um So how do these patient's present with a K I s, um it's actually usually incidental, I would say. Even working in the a m a u we get a lot of referrals from GPS who have, you know, done blood tests on someone who hasn't blood test in the last, you know, five or 10 years or whoever long. And they find that their urine crown, you know, through the roof, and they refer them in as you know, query AKI or CKD. So the big question, then, is how do you actually tell if it's acute or chronic? The very the easiest and simple ways of that. If they presented an inpatient, just have a look through on the system. What is the crowd and trend been? If it's come up according to any of those criteria, then you can say, AKI, this is more difficult if it's an outpatient, Um, if you can bring the GP and try and find a recent blood tests, if not, then you have to go off other things So one is to check this in the crowding trajectory. How is it going up or down or staying the same? Um, other things are symptoms. So if someone presents with an acute renal injury AKI, they may have, you know, recent onset lethargy, dehydration, sourness of breath and knowledge and vomiting. Auto Correa is pretty sensitive, and they may present with confusion, seizures, coma. However, someone has had CKD for years and years. They're unlikely to have those things. Um, more likely, you know, peripheral neuropathy, Doctory a, you know, itchiness, these type of things. Also, zero chronic diseases anemia can tell. Now put an asterisk next next to us because a normocytic anemia favors a diagnosis of a chronic issue because of EPO, lack of EPO production. But anemia can be caused by so many different things that I wouldn't pay too much attention to it. What is quite useful is an ultrasound scan of your kidneys. Um, if someone has chronic kidney disease, then the kidneys can appear small, shrunken, increased course, um, cortical thickness. Um, these type of things favor a chronic where someone you know have maybe normal looking kidneys or hydronephrosis. Then you're thinking something more cute. So this is your kind of approach is the one who presents with a kidney injury, then our causes. So this is really high yield. I would say that you know, it's a really good way to categorize your causes of AKI into prerenal intrinsic renal and post renal. It's a good way to give yourself a second the exam if you ever get ask, you know, to categorize in your head and take a second and have a system to go ahead with. So prerenal usually means that there is either true or an effective volume depletion. Um, what happens is that there's a lack of blood flow to the memory list to the kidneys, and that causes a reduction in G F four that results in less your creatinine being filtered and going up in the blood. And that's where you detect. Um, now, remember, this is when the common story mechanisms maybe are overwhelmed with significant hemorrhaging GI losses in true or ineffective and depletion some cardiorenal or hepatorenal syndrome. And this may sound a bit confusing because in your in your heart failure patients and liver patients, they're actually often overloaded. The flu and then you're thinking how you know how is how is this happening? It's because the fluid is all all in the wrong space. It's all the extra stuff in the interstitial fluid when it really needed in the intervascular. What happens then, is that your your your your kidneys think in the jug circle Amaryl apparatus. Oh, I'm knocking on a blood flow. I need more. They activate the rast system, and it's a vicious cycle than the intrinsic renal. These are These are ones that are harder to identify. So they include tubular. Um, and the most common one is 80 an acute tubular necrosis, and someone that you know you should know about. It's about 50% of the cases, um, for intrinsic renal. Um, it is either caused by an ischemia. So the confusion thing here is someone has a lack of blood flow due to ischemia or hemorrhage. Then they may initially present with a prerenal. But then also, if it was a pure prerenal two volume depletion, you may expect them to get better after a few days after give them IV fluids. If it's not getting better there, you know you're a crowning saying, Raised for days, two weeks. Then you can maybe say that Oh, they had an 80 an injury on top of that. So it can be caused by scheming or toxins. So toxins can be either endogenous or exogenous. Endogenous toxins include things we make ourselves like myoglobin inr out of my license or, um, light chain proteins in multiple myeloma, um, and exogenous talks. And I'm sure you're all aware of NSAIDs, you know? I mean, glycoside, drugs, radio, opaque die these type of things. Um, the way to differentiate this is when you look at your microscopy, you see these granular casts. And often, like I said, they can take weeks to resolve. Then you have interstitial causes of intrinsic renal. So that's what we're talking about. Here is acute interstitial nephritis. So this is a hypersensitive reaction. Almost always two drugs really can be due to infections. But the common culprits are antibiotics and says PPI is allopurinol. What you get here is you get white cells in the urine in the absence of infection, because this is hypersensitive reaction, and you get these classic white blood cell casts which are only seen in interstitial nephritis or pilot arthritis. If there's an infection going on, you also see eosinophil is in the urine. Other costs include R B G N would get onto that later and then vascular issues as well, and then post renal is the last one, and that's due to obstruction at any point in the, you know, outflow tract. So that can be as close as the calculi. Um, you know, or in the aortic pelvis if there's a tumor or stone and it can go down all the way to the prostate if there's a large prostate, and it causes significant backup of of the fluid so all these can cause a K I. So how do you investigate someone? So someone presented to you like this, You know, the kind of maybe presented by the G, P or whatever. How do you actually work them up? Actually, the main thing that you find out 90% of your diagnosis are by history exam. I know everyone says that it's boring, but actually is true in nephrology a lot of the time, because if you go back here, if someone's been bleeding out of anywhere, they'll tell you you know, enough to cause a renal issue or if they have enough GI losses. If someone hasn't been able to pass the urine, they'll tell you right. If someone's recently taken a new drug, you know they'll tell you if someone you know, um you know, has has heart failure has a liver failure. They'll tell you you can see it on exam with overload. You know, in prerenal an example. Be dry. So these type of things, a lot of the stuff you can differentiate here alone. Then if you can't find out still, then you can go around digging. Usually, you know, your analysis and microscopy is always a good bet. It tells you if there's cast differentiate, a lot of things blood you can request. If you're thinking about intrinsic renal, then you're digging around looking for virology, connective tissue disorders. You know, Goodpasture syndrome, rheumatoid, all these different things that can be related to inflammation and Austin kidneys like you mentioned and then a kidney biopsy. So kidney biopsy is really gold standard. Um, and when we have the biopsy sample, we use three methods to look at it under a microscope. So the first one is light microscopy is the lowest resolution. Then we have immunofluorescence. And then we have high resolution, which is electron microscopy. So the question maybe if someone's come with the A k I. So I'm sure you're aware renal biopsies and something to do lightly. You know, you're going to a hyper vascular structure. Um, you don't want to make sure you're you know you want to You want to get the biopsy. You're not just gonna biopsy everyone, So who do we biopsy? Um, usually patient's where it's been a while. We haven't found a diagnosis and their symptoms are ongoing. If we feel that we get to a certain or specific diagnosis that we could treat them for that, that we're not treating them for now and to again established chronicity. Is this an acute? Or is this a chronic thing? If we do a biopsy, we find out something with this chronic changes, Then it's unlikely to benefit from certain treatments. And again, one thing to keep in mind that these patient's are at increased risk of any sort of procedure, as it is because of their platelet dysfunction. So sometimes rarely you give desmopressin. Um, it's not really evidence base. But sometimes it's given and and we also may sometimes do dialysis to, you know, improve the general body function before we do a biopsy. If it's neither, then the management of an ache Eyes is also really important. Um, usually a good place to start if it's a severe AKI is to put in a catheter because you want to measure that urine output and closely to make sure it's not dropping. That's improving the way it should. Um, the then you can go step by step and again. I know it's a long enough list, but it's really important. I think if you are able to mention these things in your exams, it'll be quite impressed. So one thing is to treat a versatile cause. As I mentioned in your history an exam you'll be able to find usually speaking the offending agent. If it's dehydration, you're gonna lash some fluids into them. If it's a large prostate that you haven't passed urine in two days, you're gonna put in a catheter. If it's, you know, some sort of drug that you feel may have caused. You're going to stop that. Okay, then what? You're gonna do is maintain euvolemia. You're going to die. Reason if you need to. What? You're going to get my my fluids if you need to. Often with an a K I. They can get electorally abnormalities like hyperkalemia, so you want to treat that if it's there. And if the patient is sick, which sometimes it can be, um, with really high Creatinin's, then you want to involve the renal or critical team early. Um, example. If you're heading towards dialysis, you want to avoid further nephrotoxin, which sounds obvious but often in the hospital setting. Sometimes I know myself we order or request scans without thinking about the patient's you know, baseline, you know if you order a CT top or CT abdomen with contrast, you know a patient with a severe AKI can't get the or shouldn't. Then you're going to review their medallist. You're gonna hold whatever you can. That's not essential, and everything is essential. You're gonna make sure that it's a dose adjusted. If it needs to be, you're gonna put them on a modified renal diet and then constantly assessing it for dialysis. And if you do that, you know you'll hopefully fix anyone with an a k I. Then another really high yield slide. Um, your indications for hemodialysis and AKI. So if someone presents to you with an A k I. And it's severe enough, where where, what are the cut off's that's going to make you go towards the decision of dialysis? Because again, it's not a light decision. It's quite so. It sort of complications you the center line of ascot. Things like this. So a I owe you is a classic way to remember it. So a for acidosis. So usually if it's refractory, if it's not responding or if it's very severe, less than 10.1. So Esure electrolytes, uh, mostly hyperkalemia or that's refractory again, not just any hyperkalemia eyes intoxicants or like an overdose that can be dialyzed. That's Dial Izabal Oh is overload, but specifically that's refractory. And usually it's in the setting of oligo or an area, and the reason is that if you think about the way your diuretics work, they work in the nephron when urine is being made. So if there's no urine being made, you won't They won't do anything for you, so usually it's in that state and then finally, if someone has significant uremia with complications like confusion and cuff allopathy pericarditis. So this is a must to remember it's pass fail stuff. I think this is a handy slide I've left on for later. For your reference. It really some summarizes things. Well, I think you know the number one is your pre renal. It is your post renal. Everything else is your intrinsic renal. It's just a good one to look over before an exam or something. Okay, so we talked about AKI. Let's talk about the medical marijuana diseases. So we're getting onto the nephrotic nephritic syndromes here. So just before we dive into it, something to conceptualize. I always hated this because it's I think it's a terrible way to classify stuff or not an ideal way. Um, no, that glomerular diseases or pathology that affects the glomerulus can present a whole spectrum of ways, usually because we know that the function of the glomerulus is it either ends up in hematuria or protein urea or both, just from some extent. Now we can classify them, for example, like Amaryl disease and in primary renal diseases or secondary diseases. But the way that we're kind of taught and expected to know it is the nephrotic resin. If Roddick way of classifying this is just a way of grouping up these glomerular disease is to try and fit them into boxes, which I don't always fit. But let's just go with it. So the differentiated bit by you know histologically by where they affect the glomerulus and, clinically, by what syndrome of of of symptoms ends up coming. You're presenting before you with hematuria approaching your other symptoms. There's two main investigations that help you differentiate between nephrotic and nephrotic, and also between the subtypes. Number one is your microscopy looking at different casts that are present, that your analysis. You know how much protein, how little proteins being excreted and him atria and the final one is like I mentioned before, your kidney biopsy and the different ways to look. Look at the cells. So this is kind of an overview. So there's a nephrotic syndrome on one side, your folic on the other. And there there is an overlap, and even, you know, sometimes what's tricky is that in a Frolic syndrome, you may still get a bit of hematuria, which you wouldn't expect. So there's a huge overlap, but just you know what? Something for your reference. So we'll start with Nephritic. So a nephrotic syndrome conceptually is something that a disease process that damages the entire glomerulus the entire kidney. So what that causes is reduced year, for that's kind of the main path of physiology and results in other things. So the filtration bari two blood cells and both protein is lost because of the vast destruction that's going on. But you don't get massive protein Europe because your G f are so low because so much so little of your plasma is getting in due to impairment of the function that you're not able to lose as much protein. So you get here is hematuria again with the asterisk that of Young, where the red blood cell cast. This is a huge thing to remember and the protein in urine, but less than nephrotic syndrome. So they present with dark urine because hematuria swelling, edema, fatigue and protein, you're less than 3.5 g per day, so 3.5 g or first to a 24 hour urine collection. Again, that's a bit cumbersome, hard to do so. What we often do is we call a spot urine test, a protein to creatinine ratio, and this is a good surrogate marker for, you know, total protein lost. If it's less than 300 it's sub nephrotic. If it's over 300 it is a nephrotic range protein area. Or the cause is there's four here that will go into the P S G N i g a nephropathy are PGN and also Alport syndrome. So here is kind of what the path of physiology of Nephrotic syndrome. Another good summaries flat for you to go into. But what's happening is you know you're getting a reduction in G f R. Aphids inflammation. This causes on the left. You know, Hematuria's blood cells to excrete into the urine and on the right, the protein urea again. The protein urine isn't massive because of the reduced, the fr the protein being lost in the urine can cause edema. Well, what can also cause edema and these patient's is that you get hypertension. So that's the important because of the, you know, the sequestration of the fluid that you're not filtering out. This can cause edema as well. You get oliguria and these patient's and you get and acidemia. So let's talk about P s g n. So post trapped glomerulonephritis common in Children because Children guess group A, strep infections, impetigo, skin infections or throat infections. Now, the key thing this whole slide to remember of all is it is a timeline. So you usually get P s G n around 2 to 3 weeks after you've had an infection in a child. Okay, so this is important because they want you to know the difference between this and I g A which happens days after an infection or at the time of the infection. Um, so again, you can do your your You know, your microscopy. You may not see many things there, but on on kidney biopsy, you would see, you know, on immunofluorescence a granular immunofluorescence, we'll see what that looks like in a second. Usually good prognosis. Kids usually recover well, and the treatment is supportive while they have it. So next is iga nephropathy. So this is one of the most common causes of glomerulonephritis worldwide. And again, the difference is that the presentation is that you get the him a tree, a similar as before, but only days after an infection. The path of physiology here is that you have an overactive immune system. You're producing too much r g a anti, um immunoglobulins. And they end up depositing in the kidney as immune complexes in a granular way. Um, you can see here. Um, again, Um, this is very common. And the prognosis is that, you know, patient usually gradually have worsening of the kidney function, and half of them end up with end stage renal disease. Let's talk about our PGN. So this is a really severe form of collaboration. Arthritis, uh, Nephrotic syndrome, as in the name is rapidly progressive. Important thing to know about here big picture is tough, is that there's three types that you have to know on exam and the way that these three types are differentiated. Why there is three types is how they appear on immunofluorescence. So the first type is comes in a linear form, so you can see here really clean lines all along the glomerulus. The second type is granular, so I'll just show you again. This is granular and this is linear, and the last type is possi immune so policy means a positive of immune complexes. So you have nothing on immunofluorescence? Uh, um type one is due to Goodpasture syndrome. So, clinically, you have a hemoptysis on hematuria. Type two can be due to different things. Like we talked about. I g a can progress to this. You can have even PSTN and sle a Lupus. Lupus. Just a quick note can cause almost any form of communities nephrotic nephrotic any form Lupus can cause it. And then your last one, Group three, Uh, the posse immune there you're Anka Anka are PGN. So they'll be positive by the sea anchor p Anca and you treat these people with steroids, you know, an immune suppression if need be because of how severe this is. So as a rule of thumb for a nephritic and a frantic you kind of most treatment is supportive. Unless it's severe enough that you try immune suppression or that you know what responsible to steroids like, we'll get onto a minimal change. The last one is outward syndrome. Not You don't need to know too much about it, just that it's an excellent disorder with five type four collagen. We know the type four collagen makes up our whole basement membrane, so when you have dysfunction here, you get this nephritic type syndrome. But then also the classic tried is that this type of collagen in your eyes and ears? So you have pathology there as well and of course, males, because it's that's excellent. So, again, this is a summary of Nephrotic syndrome. Just keep this in mind and go back to it for your reference. It's a nice summary. Then let's not go on a frolic, so the path of physiology here is that it's not complete destruction. Where you're where you're losing is a barrier to protein, so usually the POTUS sites. So what happens here is that you have massive protein. You're a because your glomerular filtration rate isn't affected, so you're still getting loads of blood coming in, but it's not able to retain the your the proteins. All the protein gets, you know, leaks out, and you have, um, high reading on dipstick more than 3.5 g per day or a spotty or an up greater than 300 PCR presentation is a frothy urine as opposed to a dark urine, because there's not much Demetria or no him Atria. You get more significant, Adama because of the loss of protein, and then you get lethargy as well. So this protein area there's loss of protein is what triggers the cascade of pathology nephrotic syndrome. So it's another summary slide that I find really useful. So it all starts to produce protein, and it causes all the different, you know, effects we see later on. So reduce protein reduce album and, um, results in that reduce oncotic pressure so your vessels can no longer hold the fluid within them, so they'll end up leaking fluid everywhere into your tissues. You get edema. This can also be worsened by the raw system and the perceived, you know, reduction and your circulation volume. We spoke about four because the luteoalbum your liver is like, Oh, wait, I better make more albumin and what it does that it can't really selectively make album and makes everything together. So you get loads of lipids being produced in the liver as well, and you get hyper lipidemia and these can come out in the in the microscopy as fatty cast or over fat bodies. That's important. The protein you lose is really not, You know, specific. At times you can have, you know, lose your antithrombin three as well. Which is a key, you know, factor in coagulation. So you get hype or anticoagulations. You get thrombosis or hyper credibility. Um, and then you can release immunoglobulins as well so you can be predisposed to infection. So again it takes a second to know. But we'll come back to it, and it's a good summary slide. So here are the causes of nephrotic symptoms. A couple of more, Um, we'll fly through them and only, you know, go through what's really relevant. So the kind of a very common one is minimal change disease, and it's commonly seen in in Children. The reason it's called minimal change disease is because on light microscopy, you don't really see anything and you don't see anything on, um, you know, for essence as well. It's only when you get to down to the detail of electron microscopy that you start to see this effacement of the POTUS site. So you see the top image that this tall, you know, regular looking POTUS sites on the epithelium on the bottom image. You see they're all slough it off and and flat. So this causes release of the proteins and the massive protein urea. The good thing about this disease is that it's really sterile, responsive, um, and that as a favorite prognosis, Usually patients do really well after this, um, unusually in terms of the pathophysiology. What causes it? It's not 100% clear, but it's thought to be a cytokine storm after something like a viral infection. Allergic reaction to these type of things. So it makes sense why steroids work for something like that. The other one is FSGS. So think of it like so that we can kind of link these two together. In terms of pathophysiology. It's like minimal change, but maybe more worse. You can think like that because it also ends up with the face mintz of your POTUS sites. Because of these chloric lesion's. So the name is focal, meaning that only some of the glomeruli light are actually involved. As you can see in the image. Some of it is healthy segmental because, um, sorry focal, because some of the glomerular five in the kidney segmental because all these parts of the glomerular are involved and sclerosis because you see these kind of collagen deposits, um, causing sclerosis. It can be primary or, you know, unknown cause or secondary due to certain HIV sickle cell heroin, um, immune if essence is usually negative, but sometimes can be positive for I g M. Um, and the prognosis is worse than minimal change. Another common one is member nous Nephropathy. So member nous Just think about in the name again. What a result in is taking of the Glomerular basement membrane. And you can see that on a light microscopy biopsy. Um, so it's member nous, but not hyper cellular. So it's not proliferative, and that's important to differentiate. Um, again, it can be idiopathic or secondary. The important thing to know in this one is that if it's idiopathic, you'll expect to see auto antibodies against his phospholipase 80 receptor just something they may ask you in MCQ Um, prognosis, good and Children and rule of thirds and adults means a third will get better. A third will stay the same, and third will progress on to end stage. Renal disease and treatment. Again like you mentioned for most of these glomerular diseases, is supportive But if you're high risk, if it's severe, if you're losing a lot of protein, you can try and throw some immune, immune suppressive at it. So remember the last one. Remember, this is a member nonproliferative. So you get thickening of the membrane and also proliferation of cells you get hypercellularity. This is a really tricky one because it can cause both nephrotic and a frantic what you can to be honest. Um, not no, really high nothing high yield from here. Expect, except to know that hep B and hep C can be associated with type one, then the last two of naprapathy. I suppose that kind of high your yield is a diabetic nephropathy reason is because, you know, diabetes is becoming so common in the western world. Um, what happens here is that the clock oscillation of the of the basement membranes, as well as hypertensive injury causes progressive protein. You're over time, so usually this is picked up early as microalbumin urea. If you ever go to a diabetic clinic, you'll know the test for this to try and predict it coming on, and it can eventually get so bad that you lose enough protein to go into nephrotic range proteinuria. The other systemic disease is amyloidosis. So if you see on the chart on the right, there's two types a l and AM Lloyd. Um, either either one of these kind of result in kidney dysfunction unusually because the kidney filters everything out is one of the first and most common organs to get involved here. Um, the key thing to remember is that if you biopsied them, you'll see these apple green by rough engines on Congo red staining. If any of you did step, you remember that again. This is just a summary slide. A nephrotic always go to go back to a summary slide like this to remember why these these syndromes present as they do. So what does it all mean in the end of it? What is the point of learning? Nephrotic nephrotic What's the whole point? I suppose clinically not so much if someone comes to you with anything that looks like a glomerular nephritis. To be honest, you're probably gonna refer them to some, you know, a nephrologist, a renal specialist. But I suppose in terms of exams and finals, unfortunately, they expect you to know the difference in patient's in M. C. Q S and also the subtypes. So just make sure you know the major differences. Let's cover UTIs quickly because again, they're really common. Um, so important differentiation factor is that what's the difference between bacteria being present? That urine versus a UTI? Because often what we'll see and what's really common is that we as doctors, we treat bacteria just bacteria being there too often. So bacteria back to your area means that there is your bacteria in the urine detected by urine culture. Um, UTIs. When you have that as well as symptoms so often, who can get bacteria, you know, often elderly patient who live in nursing homes. Um, sometimes, you know, sometimes, um, you know people who have been catheterized recently or are currently catheterized these type of things. So you only treat if their symptoms alongside as well, because the evidence points that way. So how do we get urine? Tract infections is almost always by an ascending pathway. We have flora on our skin and around the urethra, and this comes up, and effects are the bladder or kidneys and the common pathogens. You most commonly by far as E. Coli and then less common as you go on. Important thing to know is a complicated versus an uncomplicated UTI. You may have heard this being thrown around before basically uncomplicated. Something simple. You know, you know, usually a female whose, as you can see, not pregnant, who is otherwise healthy, just as a one off UTI, and they have no other pathology. It becomes complicated when and if any man has a UTI, if anyone who's pregnant, if there's any sort of abnormality within the, uh, anatomy or function of the the your new tracked. If anyone has a catheter, if anyone has some sort of immunocompromised. So the reason it's important to know if it's something as complicated is because you treat them differently. You treat them, you know, with with more stronger antibiotics. So how do they present some of the UTI? You know, it's It's Usually everyone would know this, but it's dysuria. If it's only cystitis within the bladder, it's disarray, a frequency urgency, these type of things. Often these patient's are systemically well, it hasn't spread anywhere. They even I have normal white cell counts. Um, if it spreads up to the kidney, you can get in trouble. That's when you start to get fevers, flank tenderness. You know, um, you start to see these white cell casts and, uh, and and tenderness around the costovertebral angle, and that's gonna be serious because it can lead to sepsis as well. So who gets your new tract infections? Unfortunately, females, just because of anatomy, those who are sexually active and someone who had a urinary catheter inserted someone diabetes, pregnancy, someone like you mentioned at the start, whether your arterial reflux or someone with urinary obstruction, anything which basically promotes or allows for the ascending of the bacteria up through the attract again diagnosis we know is with uh, bacteria. You often screen with the urine dip and confirm with the culture in microscopy and then sensitivity, and then the treatment. Who do you treat? How do you treat them? There's only two times you ever treat anyone with a symptomatic bacteria uses a real thumb. Know that you usually don't treat it, but usually, but the two caveats are pregnant Patient's because there's an increased risk of progressing to pilot arthritis and also people going undergoing urological procedures like a terp procedure because, uh, back to your I can spread in the urine. If it's uncomplicated, you usually treat with a short course of or antibiotics. If it's complicated or you have pilot arthritis, then you usually need a longer course or IV antibiotics. And sometimes we admit patient's for that. Good try and speed up here. Cystic kidney disease is there's loads of different diseases present, the main one that you need to know about because of its prevalence. Is autism most dominant polycystic kidney disease? Um, for these patient's, it's usually picked up later on in life in their thirties and forties. The reason is that when they're born, the cysts are microscopic and they're not detected. The kidneys appear normal, but as they grow as they get older, these cysts grow in size and cause problems like hypertension and impaired renal function. Then you do an abdominal exam, and you start to feel these masses and an ultrasound. You can you can see these big you know, cystic kidneys are, you ought to know is the association's so that you know you can get some Barack hemorrhages because of aneurysms. Cysts in the liver, microvalve prolapse treatment for these patient's is supportive and then eventually, if they need, uh, below urinal transplant, here are the other ones for your reference. You know, you can look at them if you want to. Okay, let's fly through the cancers. Um, again, I say it's not that high yield, but then again, I think with myself and my friend got a renal cancer as our final case medical exam, so it can't It can't come up. So it's important to know one or two things about it in case you're put on the spot. So the guy either arise from the kidney or the ureter and bladder. So let's talk about renal. Cancer is the first one, and most common by four is renal cell carcinoma. If you look at the biopsy on the right, you can see on the left side this is normal looking. Um, grandma Really, um, you know, normal interest. Ishan. You look on the right. These these big you know, kind of fatty looking clear cells. So this is the most common subtype, which is clear. Cell carcinoma is the subtitle Renal cell. Who gets this type of cancer? Males. You know, people who are a bit older, 50 to 70. Smoking is a big risk factor. Obesity and some syndromes, like one apple Indo the classic triad that they talk about eczema trea, a palpable mass and flank pain. But it's almost never actually that those three triads and often patient's present late because of insidious onset. Important to know about this is that it can often present like the lung with a paraneoplastic syndrome because of all the endocrine function of the kidney. So Polycythemia do two EPO hypertension Because of run in um, Cushing's syndrome treatment for renal cell carcinoma is the most favorably surgical resection, if you can get away with it. If it's early, Stage 1 may sometimes stage three immunotherapy works well for this type of cancer. Um, usually poor response to chemo or radiotherapy. The other renal cancers, which are much less common, are Wilms tumor and renal angiomyolipoma. So I'm talking about primary cancers, and of course, you can get secondary cancers like meth, meth or or lymphomas. But we're strictly talking about primaries here, Um, for Wilms tumor we spoke about it already is due to nephro. Um, you know, Madam nephric blastema due to this, you know genetic mutation associated with the syndrome called Wagar. Um, renal Andrew. My myelolipoma kind of blood vessels. Smooth, muscle associated tuberous sclerosis. But the main one, by far to remember is the renal cell carcinoma. You may even see it on the ward sometimes, then the kind of your Terek or bladder cancers by far and away. The most common is your transitional cell carcinoma. This is the most abundant lining of the your urinary tract. Um, it's often multifocal, and it's a concept called field cancer ization. So that means you often see it in the ureters, or sometimes in Nasopharyngeal, and you know head and neck cancers, where either due to smoke or some sort of risk factors, you get this. What we call cancer is a shin or effect of all the epithelium damage of all the epithelium. You can also get multiple primary cancers in this case, so risk factors, huge risk factor is smoking. It's one of the main risk factors we see in this, and then, um, less commonly occupational exposures and cyclophosphamide. You should really be, you know, alarm bells should be ringing if anyone presents to you with painless, visible hematuria. Um you know that's you. Should 100% want to rule out anything like a cancer in the urine tract? Um, treatment as as you want Surgery, Radiation. Chemo. Squamous cell is much less common. You need chronic inflammation to be able to develop these squamous cells. And you either see that from our current stones or infection or the classic MCQ, which just a soma hemato be, um, infection, which can be seen in Africa, Middle East kind of Egypt area. And then I know Carson was incredibly rare and only rising from the urachal remnant because that's lined by, um, these cells MCQ question. Okay, second last thing Rhabdomyolysis. I mentioned again because if we do see it, it's It's a syndrome caused by Muslim necrosis. So your muscle breaks down releases all these things into the into the plasma, which causes essentially kidney injury. It can be caused by severe exercise when you're dehydrated, a crush, injury or fall or certain drugs, um, the pill present, either with the fall, with whatever the trauma or muscle pain, weakness, dark urine, so on. For example, staying a statin, you do a C K. It's through the roof and the urine dip is positive for red cells, but note that the urine dip is testing for him. So it's thinking that the red cells, but there's not actually any red cells they're usually speaking. The way to treat is a supportive Give them IV fluids, treat whatever abnormalities there, and sometimes you do need to dialyze these patient's It is severe, and the last one is CKD s. We're almost there, so again, really quite common because of the amount of patients we see with it. You know, diabetes is on the rise, and as a surrogate, CKD will be on the rise as well. So there's different stages. But what it does mean is that you have this permanently impaired renal function, which eventually does progress over time. It starts, as you know, a G f r of one stage one all the way down to Stage five, which is classified end stage. And these patient's often need to go on renal replacement therapy, and that can be done as hemodialysis. If someone has either, you know, a permanent catheter or a um, or a fistula, it can be peritoneal dialysis, or it can be by an actual renal transplant again. Remember, I mentioned earlier on that the symptoms of CKD can be linked to the actual function of the kidney. So let's go through them. So if you don't, if you're not producing e p o, then you can get enormous academia. The you know, vitamin D and calcium disregulation can result in thing called a renal osteodystrophy increased risk of fractures and secondary hyperparathyroidism impaired excretion of ways and results in this uremia as a team, Eah, cause symptoms as well. Of course, impaired asset based regulation causes acidosis. And also the major one is that your electrolytes and water disregulation results on a whole host of things specifically hyperkalemia academia, edema and hypertension. So you take a breather. That was a lot. And we went through a good few things there. Um, so we'll finish off with just going through a couple of questions. Um, just to consolidate our knowledge. And if you guys have any questions, you can let them know, Write them down the chat. I'll try and answer them if they can. Um, okay. We're still going strong here. Okay, let's go through the so question one. So I'm gonna put up the pole in a second, so you guys can respond. But, um what? Read it out for you? So there's a 19 year old male with longstanding type one diabetes. He's coming to the emergency department. He's unconscious. Um, so you can't go do much with the history, but you do. And blood gas and some bloods. And this is what comes back so sodium of 1 60 hyperchloremia high. Really high your area, you know, high glucose. You can see it there. Um p 02 seems to be okay, but there are acidotic. So at 7.1. But my question is, what is the anion gap? So let me start the polling. Believe that should work. Maybe let me know if you guys see this up so you can calculate it. And I would recommend to use the equation without the potassium. So if you can want to take your time there. Unfortunately, I think this might have covered the screen for everyone, but sure, look also, if you guys would be able to message in the chart just to see what your urine I actually don't know what the spread is. So be good to know okay. A few people have uncertain already. Okay, hold on. I think everyone answered it. Right. So 66. It's pretty rip roaring and and God, if you ask me. But let's go through it. So first of all can just informally can you guys work out with the acid based disorder is here. So remember, the first thing is to look at the B h. So it's 7.1. So I know it's acidotic and I know that only this can only be driven by too much CO2 or two little bicarb. So the CO2 is low, so it can't be That is the bicarb loads in the booths. So it's definitely a metabolic. Acidosis is their respiratory compensation. The PCO to should go in the same way. So this is low. That should be low. It is. So there is compensation. Um, and the next part would be to measure your on in Gap, which we have, and we know that it is very high. So if we use our formula 66 which is greater than 12, then we go into are different causes for an end gap, uh, metabolic acidosis by CNN has put in. Thank you for that. Um, given the clinical scenario of diabetes high glucose, you know, we're looking at a D. K. Here. And treatment, I'm sure you guys know, is, um is your is your IV fluids and your and your compensation of insulin. Usually, DK's respond pretty well, but as you can see that we're probably, we're considering dialysis in this patient because of how low their pH is and you know how high their potassium is. But let's try and treat them first before we we jump the gun. That's good. Okay, so I try to read this out. It's a bit small, maybe, but it's a question, too. So 17 year old male presented the clinic with gross hematuria or visible hematuria. He's currently suffering from a respiratory tract infection. Apparently, he had a previous episode of Demetrius some two years earlier, which was put down to by the G P to a UTI examination of notes from previously, the attendance after a rugby game revealed that microscopic hematuria and urine testing so on exam. His BP is fine. Physical examination is unremarkable. So we look at his bloods, Um, so I'll let you guys go through that. And then the question is, which is the most likely diagnosis? So I'll do is I'll launch the second poll and you can take your time breathing through it. That's good. So if you look through the bloods, we can see that the hemoglobin is mildly low. Nothing too crazy. The white cells are normal. The platelets are fine. The sodium is fine. The potassium is fine. Creatinine is okay. So bloods are fine. All we're saying that a little bit of blood approaching the urine. C three is more months. Um, I g a slight increase. So, yeah, you guys have done great. It's I Gina property. I think this gives away a little bit. You probably would have got the diagnosis without that as well. But I suppose the big question here was it a post strep When I'm gonna fight this versus an I g. A. We know it's not post strep because he's still currently suffering from the post strep. You'd expect him to get better, and then all of a sudden, him to get um, there's 2 to 3 weeks later and often like I said, post MPs g n um, you may expect to see some renal impairment as well. With that, um, not if it's, too, if it's a mild form. Like I said, Lupus or Fridays, Calm presented anything like, If Lupus is in the is the option, it's almost always could be right. But given the fact that he has, he's young. He has no signs or symptoms of Lupus at all. It's It's unlikely HSP is important because hen actually Purpura, it's, um, it's a very closely linked to I G. It's essentially Iga nephropathy as well as a rash or prepare garage. So if this same clinical scenario had this but with the rash as well, it'd be HSP and then Alport syndrome. There's no, you know, indication of any eye or ear problems. Very good. Next question. So 74 year old man admitted after a fall, Um, and he spent a period of time on the floor. So he's a long history of illnesses on examination. He's obese with the BP of 1 10/75 pulse of 100 and 10 bucks, 38.5. So he has a fever where sparkly exam reveals evidence of a right, lower lobe consolidation, and he has no kind of trauma. So this is his work up is E. C. G shows, Sinus rhythm, tall T waves and no ST changes. Chest X ray confirms what we heard on exam. Hemoglobin's mildly low white cells are up. I'll let you guys go through the rest so I'll pull up the pol. So question is what diagnosis best fits with the clinical picture? Yes, perfect. Well done. So if you look through the Bloods here, um, we can see that his white cells are up to probably due to infection going on. Platelets are fine sodium. Potassium is very elevated. 6.7 urea and creatinine are up in a C case through the roof. It's greater than 1000. Important part here is that there's his urine dip is positive for blood, very positive. But there's no Red Cell C and microscopy, and that's what gives it away in this scenario. So that's classic of a rhabdomyolysis. Um, he has a risk factor. Freddie has a fall with a long life, so being obese, he's laid on, his muscles have broken down. They've caused this, uh, this, you know, after my license, the myoglobin to cause an AKI to his kidneys as well. So likely as an AK. We don't know his prior picture. Gram negative. Sepsis. Um, I suppose this is maybe alluding to the fact that it is it a sepsis, second to the pylon or fighters or something, but we know it's from the lungs. Unlikely Acute tubular necrosis, second hypertension. His BP seems okay at the moment. Doesn't mean it wasn't before. But given the CK and everything, it fits the rhabdo polymyositis. You may also see a really high CK, but, you know, you expect to see maybe someone with muscle pain or proximal myopathy for weeks to months, not something like a cute like this. And I keep myocardial infarction. Um, unlikely, given the fact that there's no ST changes on the C G. So same scenario, but different question. I'll put the next poll. So what would you want to do for this patient's trade? What's your first port of call here? What do you want to do from? So the options are give him antibiotics. Give him IV fluids to resuscitate him. You try and contact the next of kin to find out what happened. Give him 10 mils of 10% IV calcium gluconate or get an MPAT Falls Risk assessment for you. So this I suppose it's a strictly renal what I covered. But I think it's again important stuff here. I'll give another few seconds spread of answers this time. Okay, let's go through it. So the answer to the back onto this question or answer is that any one of these five, all of these five should be done for this patient. He definitely should get any products you should get. IV Fluids Association. We should contact next to kin. At some point. We should correct, you know, or or temporize the heart to make sure it's not affected by the hyperkalemia. And we should get empty the fall assessment So all of these are right. But the question is, what's your first type of management? So it's kind of I see there's between two IV fluids or or calcium gluconate. So in this scenario, because the patient has hyperkalemia with E c G changes, essentially, what this means is this patient's you know Myocardium is unstable because of the hypercalcemia. Now he definitely does have a rhabdo, and you definitely do need to treat that. But what's going to kill him quicker than the rhabdo is this electoral abnormality cause them to go into arrhythmia arrest. So in this case, you go first with calcium gluconate. So for those who don't know 10 mils of 10% calcium gluconate is your emergency treatment for hyperkalemia severe hypoglycemia hyper clean with TCG changes, it doesn't treat or correct the hyperkalemia. It just stabilizes the myocardium. Your next step is insulin and things like that. But it's kind of reality. I understand. It's not realistically, you probably give them calcium gluconate in one vein and the fluids and the other veins. So but initially you should be thinking about calcium gluconate. Then your next step will be to IV fluids. Um, this is just what I'm used to. But of course, you know, use whatever hyper claimer protocol is according to your local trust. Okay, we have a couple more questions. I'm waiting for time. Not great. Okay, We'll fire through them quicker this time. So 54 year old accountant presents to the emergency department with nausea and vomiting. Associated lethargy. So history of asthma well controlled with an inhaler. No other medical history. He doesn't smoke but drinks up to 30 units of alcohol Week, most on the weekends, and his obs are as follows the temperature histories are going to BP is 108 68. Heart rate, 92 an exam. He appears to be slightly dehydrated, but there's no other abnormalities, and his blood test starts follows. Question is, which one of the following of the below symptoms or findings would be most suggestive of a K I rather than chronic renal failure. So which of these following fight? Which would you think would be President's AKI as opposed to a chronic? So I just put up the pole. Maybe a little bit more tricky. Let's give it a few seconds. So if you look at the Bloods anyway, we can't see that is Urea is up and it's cracking this up. We know that blood is carried out a year previously was 76 so it's seeming like an AKI, but we don't know for sure. But with this treat it as such. Potassium seems to be okay. The question is, which one of these of the below would you more likely to see in an AK or an acute kidney injury as opposed to chronic. Yeah, good. So oliguria Very good. It's it's This is a tricky question. So the rest of them you'd expect to see in chronic so raise PDH you'd expect to see, uh, secondary hyperparathyroidism after CKD after, you know, the disregulation of calcium peripheral neuropathy could be due to the uremia you see in in CKD Patient's. But the chronic uremia nocturia also just one of those things in CKD Patient's and see and small kidneys, shrunken small kidneys is another thing that remember, we see, um, on on in chronic patient's with with CKD. So remember, back to the slide Um, oliguria. However, if someone has oliguria, that's a bad sign. It usually means something acute is going on. Someone with a chronic stable kidney disease wouldn't present with the lower urine output and something without some worrying. Good. Most of you got that right. Question six. A bit of a theoretical one. You'll hate me for this one. Um, hold on. Is it in this new year? This is a quick one. Um, bit of physiology. I'll let you read through it So this is the Juxtaglomerular apparatus, unfortunately, was able to show it earlier, but you can see here that it's kind of this area of triangular area between the Afrin d friend art era on the Michaela Dinsa. So you can see these are specialized cells which control both water retention and flow through the glomerulus. They also secrete Renan. Um, but which sells do that? Yeah. If you guys get this right, I'll be quite impressed. Yeah, very good. You're all getting all right. Number four. So going through them, the micro dinsa is apart. As you can see of the distal tubule, you see these dark yellow cells? It's not the arterial. Uh, Renan is not secrete at the Macrodantin secreted by these granular juxtaglomerular cells you see back again around the Afrin arterial Is Brennan secreted in response to raise sodium level of the McLaren, Says, Oh, no, um so raise sodium level. Michaela Dinsa causes, um, could change in the arterial, so cause increase in blood flow to the kidney. Um, what is what does cause when in release is a fall in pressure in the back receptors in the Afrin arterial. Very good. That was a tough one. Okay, so just I think there's two more. So, actually, I think in the interest of time, I've already taken about an hour and a half years of time. I'll just fly through these myself. So for this one, a 7 10 year old man is admitted hospital feeling generally unwell, he's developed a fever and diffuse erythema this rash over the last few days. So that's important. Fever and a diffuse rash. You had some systemic symptoms. Is your announces positive for blood on protein? So already we're kind of thinking of a certain way. Blood test show raised creatinine and eosinophil's. Okay, So the G P started him on a new medication two weeks ago, but he cannot remember the name or indication. So everything altogether he has blood and protein. You're probably thinking of some sort of glomerular glomerular disease. They're likely is a nephrotic or nephritic. Um, we don't know the exact, you know, Claritin or blood. Um, but given the fact that he has eosinophil's, his creatinine is increased, which indicates a reduced EFR. Remember, we said reduced EFR is key. And Fridays or thinking of a glomerulonephritis, um or a a possible tubulointerstitial disease either. Okay, so it could be a t n or or or or an interstitial disease, so that's a differential. But we see he has eosinophil So Eosinophil's as well as having a fever and a rash that all indicates towards acute interstitial nephritis as a diagnosis. So which one of these drugs that he's currently on? Would we be happy to continue at present, given that we suspect that so allopurinol amoxicillin, diclofenac, omeprazole prednisolone. So I can tell you the first four big no, no sterile pine perpetrators of a i n so prednisolone is a correct answer because it doesn't cause a i n. And actually, it's one of the treatments for severe I I am. So that's it. Second last one, um, 51 year old man with a K i he's developed fluid overload. Um, this is kind of a high yield one because of dialysis. So he has a k i. He has fluid overload. Um, and you've gone to assess him. You've done a B c. D. So his airways fine, but he's a bit confused. His breathing is a bit up, and he's on oxygen. And you heard by basal craps. He's a bit tachycardic, and he has a friction rub. So he's G. C s 14 because he's confused. His temp is fine, so these are his A B G results. You can see he's acidotic, and I know that can only be caused by a high CO2 or a low bicarb. So which one is it? Bicarb is a little bit low, and P CO2 is a little bit is normal. So is a metabolic, um in nature. And then is there some respiratory compensation? So this could be a mixed picture because the respiratory isn't compensated Or it could be just, you know, initial initial disease anyway. So which one? Which one of these is an indication for urgent dialysis? So is urea is very high, as crown is very high as a lactate, It's okay. So his potassium of 6.3, which isn't mentioned here a pH of 7.28, crowning of 7 to 9 urea 53 or by basal crackles. So to answer this, what we do is we go back to a IOU. His pH isn't low enough. It's not less than 10.1 potassium is 6.3, but we try trading. It's not very severe. 6.5 is sometimes a cut off, creating you never acutely dialyzed based on creatinine. Your rehab 53. Maybe let's go back to it by basal crackles. So we're talking about edema, but we don't know if it's a refractor or not. I don't know if they've treated it, so the definite indication other, maybe relative. The definite indication is your urea with symptoms. So you remember that uremia with complications like encephalopathy, which he has, and a urine make pericarditis, which it sounds like he has, is a definite indication for dialysis. And let's finish off here with the last one. So 57 year old woman has become hypertensive tachycardic two hours after a lap partial gastrectomy for a tumor. So blood glasses are as follows. And what's the most likely diagnosis? This one I might get you guys to do just because it's the last one. And take some calculation, so just take your time with it. Um, you can see the acid based disturbance on screen there on the answer. What you think? Yeah, uh, so it's a bit of a tricky one, but we'll talk to it. Just you can try, try and answer whichever one you think is right, and we'll talk through it. So this one is bringing a little bit of respiratory medicine into it as well, as well as renal. Okay, so let's just talk through it now. Um, thanks for everyone who did answer. Um, so this lady's two hours POSTOP and she's becoming hypertensive and tachycardic. What we what we see on the A B. G. So we see that they're let's. So there's two things looking, maybe G. Obviously you've had the respiratory lecture already. You can. You can talk about respiratory feel there's different types and what we're talking about today is the acidosis versus ankylosis, so pages low. So it's an acidosis. We know that, and again, let's go back. They can, either because it's too much CO2 or two little bicarb. So there is too much. So two in the bicarb is normal. So this is a respiratory acidosis because of retention of CO2. Okay, so already we know that when we spoke about are different causes for respiratory alkalosis and respiratory acidosis, he said. it's either do too hyper or hyperventilation. So in this case, a respiratory, um, acidosis, likely due to hyperventilation. But let's not taking it. We don't treat numbers. We treat patient's okay, so understand that if you look at the clinical scenario, it could definitely be any of these. And you be concerned for the other ones, like pe long at Alexis Pond radium. It could be any of them. Let's look a little bit at the respiratory point of view. So is it a type one respiratory failure or type two? So first we look at the P 02, so it's low, so you know it's either one of the two. Okay, so type one respiratory failure is low oxygen with normal or low CO2 type two respiratory failure, which means you're radically breathing. Type two. Respiratory failure is when there's low oxygen but high, so to see you're retaining. So that means that there's some sort of ventilatory problem. So those two things in conjunction indicates it's all a ventilation problem and do type of ventilation. Okay, why would someone like this hype eventually post up a few different reasons? Number one pain. Someone's just had surgery in their stomach. They won't want to take a deep breath will cause pain everywhere. Number two. They are usually on loads of narcotics, like opioids, and that can cause respiratory depression. Which is probably what's going on here, given that she's hypertensive as well. Um, And then, uh, the anesthetics as well. The anesthesia, You know, she could be recovering from that. Still. Now, it could still be a pe upon me, a Dema along with Lexus. But you wouldn't really expect to see a high p o p CO2 with these, you'd only expect to see a low p 02 now, late stage of pulmonary embolism. When you've been breathing so much, they become tired. Then you can get this picture. But it's only been two hours. So unlikely, I think that's it. Take a deep breath. He made it through. That was a lot of an hour and a half, I think total. So, thanks to everyone for listening, Um, if there's any questions, you can pop them into the chat box there. Um um, I can try and answer them otherwise, um, I think the main thing I was told to say was that if you wouldn't mind filling out the feedback form, it helps us out a lot to try and find out what we should tailor towards. You guys. You know what? What suits you? Um And I hope I hope you You got something from that? I know it was kind of a quick whistlestop tour of everything, but I think we kind of covered mostly what was relevant to you. Um, but yeah. If you have any questions, you can pop them in the chat. Yeah, I'll be around for a couple minutes anyway, if anyone on styles anything Um okay, no problem, guys. Thanks for having me. I think in Italy it is recorded. Um, well, there was I just send my email into the chat. If anyone wants to show me any burning questions or anything, you can even try to answer them if we can. But, um, that's it. I think that's it for me, then, um, thanks to name and for for hosting. Thanks for everyone for attending. Um, I think this will be the slide should be available, and it should be, um, the recording should be up as well