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Okay. Welcome, everybody. Uh, I'd like to introduce you to, uh, doctor John Vogel, who is going to be speaking? Sorry. What are you guys to be speaking on on hyponatremia Hypopnea, Nutri, mia. And, uh, just if you haven't already done so can I ask all the students to put your name, medical school and your year of study and your city into the into the chat? Um, and away you go to to Vogel. Okay. Hello, everybody. Um, let me just get this up. So, uh, uh, let's see if I can just get rid of this high pedal. Uh, okay. Just I'm sorry. I'm just trying to get this up and running, okay? Can you see this? Can you see this? Hello? Yeah, we can see that. Ok, sorry. I just want to get, uh okay, so Hi. My name is Doctor John Google. And I am, uh, recently retired consultant. Any case consultant, intensive care, medicine and anaesthetics. And the top topic I want to talk to you today is about, um, disturbances in plasma sodium, in fact, specifically hyponatremia. Now, the reason I want to talk to you about this is this is a topic that everybody learns and almost everybody I know, including myself, thought we understood it. We go back, we see a patient a week later and we have to go back to the books again because we forget it all. And I was getting fed up doing this, So I thought, maybe I have to really understand what I'm doing instead of just memorize. Plus, the way most of this is taught is actually pretty is not very helpful because they talk to you about categorizing people into hypo hyper and normal bulimia. And we know that's very, very difficult, if not impossible to do so. I'm going to try and deconstruct this topic and make it a bit more interesting and maybe make it a bit more understandable so you can work it out next time and not have to memorize. Okay, so this is about water intake and water excretion. So here's a clinical case that I'm going to start with, and at the end of this talk, hopefully we can understand why this this case occur. It's a typical case. You'll see, uh, an elderly woman who's admitted to the word with breathlessness pulmonary suspected pulmonary edema from cardiac failure. He's known to have cardiac failure, and he's oliguric. Her sodium is 1 34 when she arrives. They treated with high doses of diuretics frusemide, and it has a good effect. Four days later, while she's in the ward, he seems better clinically. But her serum sodium is now 119 million volts. Why? So we'll come back to this case and we'll try and figure out what's going on here. What are your treatment priorities? This this is very important. And as an intensive care doctor, I saw a lot of people send me patient's with severe hyponatremia and, um, almost always badly managed. So we'll try and help you not manage his best. So what's the, uh, outline for today? We're gonna talk about an introduction to this. We're gonna talk about the normal physiology because you have to understand this. This this is going to be the foundation on which you are going to be able to understand how this works. Um, mechanisms and then treatment. Yeah, So the introduction here are some basic concepts we have to understand before we can build on this, uh, on these principles. So osmolality are the total number, or total concentration of all particles in a solute. But we're interested, though, is effective osmolality, or what we call tennis itchy. And that's the osmotic gradient due to salute that do not cross a cell membrane. So, for example, if I gave somebody urea, the urea can raise the osmolality, but not the effective osmolality because it crosses the cell membrane. So by introduce something like urea, it'll be high, high concentration of the serum. But it will be equally high inside the cell that does not count as tennis city. For example, if I'm if you're into cooking and one of the ways to make a tomato or tomato sweeter is to put salt on it and let the water be, uh, removed extruded by the use of the osmotic gradient, leaving the sweeter tomato behind. Same thing with an aubergine. In this example. You want to, you know, grill over genes. You put salt on them, leave them for 20 minutes. This water is extruded. You wipe away the salt and water, and now you have a less soggy aubergine, so it makes it easier to grill. That's exactly what we're talking about except we're talking about cells, not over genes and the main indicator of Oz modality in the extracellular fluid, which is what we're talking about today is sodium, and the reason it's important is that if you, um if you're imbalanced in terms of osmolality, so if you're hyponatremia, you have a too low a sodium in the extracellular fluid. That means that the relatively higher tennis itchy inside the cell, for example, in a brain cell will attract water. So the opposite of what you see with the over gene and your brain swells will swell. And therefore you get raised intracranial pressure and your head hurts yet a brain. Uh, you get a headache or worse. So, um, let's talk about some rules of the game, first of all, and this is often misunderstood. Sodium balance determines your volume status. Okay, So even though we're talking about hyponatremia hypernatremia, it's not sodium that determines that it's water. Water determines your tennis itty. Okay, so when we talk about sodium were talking about volume status. So we're talking about hyponatremia, hyponatremia. We're talking about water balance. So a common mistake I see are people with hypernatremia so too much higher concentration of sodium. And what some of the doctors I see say is, Oh, we must put them on a low sodium diet. No, you must give them free water. Okay, so it's water we're talking about. So let's look at some normal physiology. So normally, your your normal serum osmolality is of the order of 285 million osmos per liter. Let's say 2 85 to 92 92. Let's just keep a round number two a 2 85. So your maximum urine dilution. So if I drink as much water as I can drink and you go to the bathroom and I'm gonna I'm sorry, I'm gonna use the medical term P Okay, because I find it easier to remember. So you're gonna you're gonna p until it comes out almost clear the maximum you can dilute that serum. Osmolality. It starts at 2. 85 is $50 million moles per liter. So when you you drink a lot and a lot of water or beer or whatever you're drinking and you're starting to pass, it looks like almost clear water. You're actually you have an osmolality maximally diluted. If everything is working fine of 50 million osmos polluter. That is 1/6 of your serum osmolality so your body can get rid of a lot of pre water. On the other hand, you just crawled through the desert. You haven't had anything to drink, and you go to the bathroom and you p what looks like t strong tea so you can maximally concentrate your urine to about 1000 200 millions most per liter. So that's four times your serum osmolality so you can see your kidneys with their functioning correctly. Um, can can either get extrude a lot of extra water if you're taking extra water or you can save as much water as possible. So you go from 50 to 1200. How does it do this? So what is the most? What are we can excrete? Well, it depends on your salute intake, and this is one of those aspects that is almost always forgotten, and we'll look at this right now. So let's say that is your maximum dilution. So that's a leader of urine in a bottle, a leader leader bottle, and that little dot is the, um is the millions molds. So your maximum dilution, as we said, is 50 million Osmonds per leader. So that's the best you can do. So if you are someone who has a full English breakfast, a really solid, you know, a solid appetite, and you take in, Let's say, 900 million Osmonds a day. Most people don't know how many millions moles they take, but that's the order of magnitude of what we can eat. We have a really typical western diet. That means that you can excrete 18 bottles of of, uh, of maximally dilute urine. Okay, so that means if you have that saw you, intake of 900 million is most a day. So it's 900 divided by 50. That's 18, so you can maximally excrete 15 liters a day. Now if you're an old lady in the ward, Uh, you're not well, and you can only eat, say, tea and toast. You might take in 50 100 let's say 100 and 50 million osmoles. So nothing like the the meal you see on the left. That means 1 50 million osmos, uh, is taken in. You can only excrete a maximum of three bottles, so it's 1 50 divided by 50. That's three bottles of urine maximally diluted a day. That's the maximum. And the thing to remember is, you cannot peep your water no matter how hard you try. So let's see. You're you're taking in 100 50 million millions miles a day and you know that you can only X create three liters a day. Let's say you drink four litres because you're thirsty. Well, you can get rid of three of the four liters, but one of those leaders stays on board. You can't get rid of it because there's no salute to go with it to accompany it. So that means you are now becoming more progressively more and more hyponatremic because you're you're accumulating water and you're gonna drop your sodium. So your solu absolutely invaluable. And one of the treatments people talk about with hyponatremia is to give someone urea. And urea is just another way of getting solu. You can just give somebody you know, uh, feed them. And if you ever go to Belgium and they offer you champagne, ask him if it's French or Belgian champagne because Belgian champagne is is urea in sparkling water with a bit of coloring added to it to make it more palatable. And that's not what you probably want, cause you're a is pretty disgusting. So So it's important. And don't forget when you're sick. I don't know about you, but when I'm sick, I have the flu. For example. I'm not hungry, but I am thirsty. So if you're not hungry, you're not getting to sell you. But you're thirsty, so you're going to overwhelm your system. You may get up in the treatment, so that's really important to remember. So let's look at how your nephron actually does this. So here is your nephron, and you've just filtered, uh, your serum. So it's 285 million Osmonds. As we just said, that's your serum osmolality In the proximal tubule, you're gonna re absorb about 70 75% of your filtrate in an isoosmotic way. So you're gonna get equal numbers of sodium and water molecules, so you're basically not going to change the concentration in the filtrate. This is going to re absorb volume and they go together. But now, as you go towards the the loop of Henley, the ascending loop of Henley, you've got sodium pumps. We call them diluting segments. And what they're going to do is these pumps are gonna start separating the water and the filtrate from the sodium and chloride and potassium. So what happens here is here's your filtrate. And as you go up the loop of Henle E, you're going to start pumping out sodium into the interstitium and you're left with a more dilute filtrate. And in fact, when you get to the top of the loop of Henley to the distal tubule, you can see that you're now got a very dilute um, Filtrate. And it's 50 million Osmonds at that point. That may ring a bell now, as you go down in through the interstitium from the top to the bottom. So from the cortex to the medulla, you're getting a higher concentration of sodium because the way the pumps are working is have a counter current mechanism. So what happens now is you've got you can see 306 112 100 million oz, moles of of a high concentration of sodium because of the pumps, so they're excluding it into the interstitial outside of the tubules. So now, as you pass through that interested in which is more and more concentrated If you have a D h anti diuretic hormone you This opens what they call aquaporin. So if you want to think of it in a very silly fashion uh, a simplistic fashion it's like you have doors as you go down. The collecting collecting duct goes down through the interstitium and you have these doors and these doors are called aquaporin, and the key to these doors to open these doors is a a D. H. So if you have a d h, it opens the doors, it exposes that filtrate to the high concentration of interest. Ishan of, say, 1200. And of course, your water now can leak out, leaving a high concentration of of solu and it comes out at 1200. Now you can see on the top if you're maximally dilute its 50 and if you have it maximally concentrated, it's 1200 that rings a bell. I hope so. Let's look at maximum dilution. So here, in this case, you've your pumps are working. You've got so firstly you got filtrate, you've got the filtrate going through the ascending loop of Henley. It's the sodium pumps are pumping out, the the separating the water from the salute you get to the top of the collecting duct and the distal tubule. It's got an osmolality of 50 and let's say you don't have a D H. The lock is still locked, the doors are closed, and so the filtrate comes out exactly unaltered, so it comes out at 50. That's maximum dilution. Okay, so I think you now understand how how you need various aspects of the nephron to maintain your homeostasis. You have a maximum dilution and maximum concentration. So how do we control our sodium? Well, it's our intake and our excretion, and it's the water that's the adjustable variable here, and often there are multiple calls is that we have that causes hyponatremia, so you may have a reduced intake because you're not feeling well. Um, you can't maximally dilute your urine because you have kidney disease or you're on diuretics. Um, there are lots of reasons we'll go into water intake thirst, a very powerful sensation that we must not overlook. In fact, there's an adventure who's well known to British television viewers whose name is Bear Grylls And he's, uh he's a bit of, uh, as I say, an adventurer and one of the adventures he talked about drinking his own P. And I assume it's because he was thirsty. Um, but he likes the taste. I don't know, but anyway, that's just thirst is very, very powerful. So how do you get rid of water? Well, you going back to what we just talked about. You have three steps that you have to accomplish to generate most dilute urine because we're talking about hyponatremia. So too much water. So we're talking about diluting your urine here. So first of all, you've got to have filtrate delivered to the NEPHRON. So if your glomerular filtration rate is low, um, so you have your hypovolemic, for example, and you're not getting production of of filtrate and hence urine. You can't alter your filtrate, so that's obvious. You have to deliver the water and sell you to the to the nephron. Secondly, you've got to have functioning diluting segments. So, in other words, those sodium pumps we talked about to separate the the, uh, salute from the water in the filtrate. And thirdly, you've got to have, um, the ADH, which is going to open those doors or not. And if they if they open the if they open the doors Um, sorry. If they don't open the doors, you, uh you won't be able to get rid of the water, So let's look at some mechanisms now. So, as I said earlier, what most textbooks tell you is to divide people into normal hypo and hyper polemic. And I find that very not very helpful because I can't tell someone most people unless it's really gross. So I'm gonna try and use a different mechanism to understand what's going on, and this is gonna be theoretical. But at least I'll give you, um, an idea of how to approach a patient like this. So we're gonna look at patients who either have a low ADH anti diuretic hormone or a high a d. So, first of all, a d h. I don't know about you, but I always used to get a d A mixed up and the best way for me to remember it adds water to your body. A d h. So if I'm hyponatremic means I've got too much water. Remember we said your sodium balance is gonna be determined by water. Is your water that counts? So if I If I'm hyponatremic, the last thing I want to do is add even more water to my up by body. So I don't want a DHA in this case if it's inhibited. So if I'm hyponatremic, it ought to be inhibited. I will produce maximally dilute urine. So basically, I am not going to open the doors, uh, in the collecting tubule. And so the urine is going to come out at 50 so its maximum dilute if it's stimulated, then it's going to open the doors, the aqua porn's and it's gonna let the water, uh, aggress from the, uh, collecting tubule and you're gonna produce the maximally concentrated urine. Now, there are other stimuli that are not just based on your osmolality. They're non osmolality stimuli. So things like a low BP, a low, effective arterial blood vine which will come across I'll explain to you in a second very important concept, often misunderstood. And there are other short term problems, like stress, post operative cases, pain exercise, low cortisol, low thyroid hormone, et cetera and one thing to remember. That's very very important. Volume takes precedent over osmolality. So if I am hyponatremic, But I'm also hypovolemic, my body is going to try and retain water even though it's going to make me even more hyponatremic. So volume will take precedent over osmolality that's important to remember. So let's look at a low a. D. H, um, part of the algorithm we're going to look at here. Okay, so this is going to be the theoretical construct so low A D. So how does that work? Well, here, you got somebody who's taking in too much water. This is called photo mania. And if it's beer, it's called Beer Poteau Media. So let's say I have a normal intake, a normal diet, and I'm going out. I'm gonna drink as much as I can and I drink. Let's say, as you saw earlier, the maximum solute I can take will be, um, say 900 million millions moles. That means I can produce in this example 18 leaders and I drink 20 liters. Well, that means two of those leaders I can't excrete, so that's going to cause my my sodium to drop because I've got too much water that I can't get rid of. What about If I have two little solute, we'll just explain that. So if someone's on a tea and toast diet, they're not feeling well. Old lady who's not very hungry. They often don't eat a lot. They haven't. If you need salute to get rid of that free water, if you don't have a solute, you can't get rid of that free water, not to the same extent that you might have to. So those two examples says that everything's working as it should, just not enough. So you're just basically overwhelming your system. And of course, for you to be able to, um, produce dilute urine to get rid of the extra water, you're going to have to have normal your filtration because if you don't produce the filtrate that can be worked on by the nephron. You can't alter that, uh, that that get rid of that free water. So you got to have, um, go may or filtration. So G f r. You have to have something going to the kidney for it to alter it. And so if you have, say someone who's got a raise crap need because your kidneys aren't producing the filtrate, then that will also be a problem. And that's all on the side of a low anti diuretic horn. So you haven't you just don't have enough filtrate to get rid of the excess water. So those are the examples you get with a low anti diuretic hormone situation. And what about a high anti diarrhea Cormack? In this case, you have got concentrated urine. Now, if you have hyponatremia, you don't want concentrated urine. You want to get rid of dilute urine so you're basically retaining order, which is not normal. So what's causing that? Well, one of the causes is a low, effective arterial blood bone. Now this is a subject I'm gonna have to spend a few minutes on because it's really important. It's often not understood at all, and it's actually very useful to understand this for other clinical conditions. So what is the effective arterial blood vine? It's the volume of arterial blood that's effectively perfusing your tissues. It's not your blood volume. So if I say I have five leaders of blood in my body, most of that's my venous system at least 70%. What I'm interested here is the blood is the amount of blood, the volume blood in my arterial system, which is a lot lower. They reckon it's a It's a dynamic quantity. It's hard to measure. They reckon it's about 700 mils, you know, 70 kg person. That's a ballpark estimate, so it's not easy to measure, but it's not. It's not your five liters. It's a relatively small volume in your arterial side. That's the That's the key, the key word here. Normally, it is coupled to your extracellular fluid. We call E C f. So if I have say, really bad diarrhea and I'm really dehydrated to the point where my arterial blood volume is is, um is low, I'll look very dehydrated. My skin will be very dehydrated. My mouth mucous membranes were obviously very dry. That is coupled. So my e a b v, my ex effective arterial blood volume is low and my extracellular fluid is low diarrhea. I'm getting rid of all this fluid, so both E A, B V and E C f are low, but in many conditions that we deal with in in the wards in in the hospital, we have uncoupling, so you can have someone, for example, with cardiac failure, CCF, congestive cardiac failure or chronic cardiac failure. What happens with them if you look at them? They're a dermatitis. They're not dry. They're not dehydrated there, Des Metis. So you have a low, effective arterial blood volume. And yet there a de metis. So it's uncoupled. Unlike, um, someone who's lost volume. So what are the kind of illnesses that will cause that? Well, congestive cardiac failure, cirrhosis, sepsis. These are the kind of classic modern illnesses we see in hospital. So that's really important. You have coupled and uncoupled. Um, E b v And how does this work? This is really quite important. So your body has evolved to defend against a low, effective arterial blood on, and we have three hormone, or neurohormonal systems that you know that defend our effective arterial blood vine. So one is nor adrenaline. What does that do? It directs blood away from your kidney, so you're not going to be losing fluid, and you're going to be directing your blood towards your heart and your brain. Secondly, you have the rast system which produces andrio Tencent to and what is that going to do is going to retain water. It's gonna retain salt because don't forget, we said salt sodium chloride is determines volume status and it's gonna make you thirsty. So you're gonna retain water, salt and thirst. So it's trying to retain the kind of crystalloid volume that you would be losing. And thirdly, you have anti diuretic hormone, and people often forget that one and that you retain water, not salt, just water and you're thirsty. Okay, so you can see here that if someone has a low, effective arterial blood volume, those three neurohormonal systems will kick into Axion. And what's important to recall is that a d h if I'm so if I'm dehydrated and only dehydrated. My effective arterial blood line has not been is not low yet. I'm just dehydrated cause I've been out running. I'm sweating my sodium increase in concentration. It'll make me thirsty and I'll retain water. But I will not retain salt in my urine. Okay. And that's important because one of the ways to know if you have an a low, effective arterial blood volume is to look at the consequences of these enzymes of these hormonal systems, and so what you can do is look at the urinary sodium. If it's low, you can say it's below 30. If it's low. That means that your entry of Tencent to your grass system is working because it's responding to a low, effective arterial blood line. If, on the other hand, I'm just dehydrated, then my serum sodium may be a bit high. My urine osmolality will be high because I'm retaining all this water so that what's left is concentrated. But I won't have a low sodium in my urine because I haven't got a low, effective arterial blood line just dehydrated. So that's the difference. So those are the three systems. And as we said, if you have got a low effective arterial blood volume, you save salt and water sodium and water, and you You given these cases is volume, uh, in the form of crystalloid crystalloids, just water and and and sodium just, you know, being a bit more philosophical. Now about all this. Why do we actually worry about this? What? How do we get this system to save our effective arterial blood line? And so what caused our death, Say, 11,000 years ago? Well, it was blood loss. We are engineered to defend our effective arterial blood volume against being attacked by a saber toothed tiger and losing blood. But today, what kills us is not usually well, it can be trauma probably quite relevant today. But some people, but are things like smoking related illnesses and alcohol related illnesses, modern scourges of medicine. And in both those cases, you can have a low cardiac output and either low cardiac output or vasodilatation in the case of cirrhosis, sepsis or pregnancy. Because what happens is that your you have stretch receptors in the aortic arch and the carotid, um, arteries. And if you, if these receptors are not being stimulated by not stretching, then they're saying we must have a low cardiac output or low BP or both. And when those cases so there's where your receptors will be located, you're going to get those three neurohormonal systems come springing into Axion, and you're going to retain water. You're gonna retain salt, you're gonna be thirsty, and you're gonna redirect blood away from the kidneys so they don't produce filtrate. And you're gonna hopefully restore your arterial circulation. That's why we're, uh we've evolved to be this way, but it was a nickel for blood loss. So take care of you how this can actually be very useful in other clinical settings. Here's somebody who has decompensated cirrhosis. If you have decompensated cirrhosis, you get severe portal hypertension. You get a back pressure on your intestines, you get bacterial translocation. You get for other reasons as well. Severe splanchnic, arterial vassal validation. So if your vessels dilate the blood in your thorax, it's got to something's got to fill that dilated space. The blood from your thorax goes down to your splanchnic. So you're going to get a very low. You're gonna get a signal saying we have a very low, effective arterial blood volume. You activate your sodium retaining and vasoconstrictive systems. As we just said earlier, you're going to retain salt and water, and you're gonna produce societies, and eventually you'll produce what they call the Hepatorenal syndrome, which causes renal failure. And so one of the treatments of this is you give albumin to refill that space. You give Turley Preston, which is going to cause a splanchnic vasoconstrictions to force blood back in the thorax and so you can kind of and then you give spironolactone so you can you can sort of work out from this. And the same thing applies to heart failure as well. You can work out from this how what you're trying to achieve. You're trying to counteracting your your body's attempt to restore effective arterial blood line. Okay, so that was, uh, now we said earlier that effective arterial blood line that's too low will, uh, will cause, uh, will cause a raise in ADH. As you saw. And there are two causes either your coupled with your extracellular fluid or your uncoupled. So if you're if you're in both of those cases, you're gonna have urine that's concentrated because you're retaining water and it's going to be poor and salt. So you measure the urinary sodium is going to be low because your body is trying to retain. Remember, we said the rast system is the neurohormonal system that will retain salt unlike a d. H. Because your body quote unquote perceives a low, effective arterial blood volume and volume trump's osmolality. So if you're hyponatremic and your body thinks it's, it's, um e a B v, it's effective arterial blood volume is low it's going to say I'm sorry. I don't care about the hyponatremia. I've got to protect my blood volume. So it's gonna retain. It's gonna retain water and salt, on the other hand, if you have renal losses, So if someone's got a fixed dilution, So if they're in chronic renal failure or if they're on diuretics, which is much more common, you're gonna fix your dilution. So what happens here? So let's say, um, on diuretics and we found diuretics. The sodium pumps that separates the salute from the water in your ascending loop of Henley doesn't work. So the filtrate that comes into the sending loop of Henley, which is remember we said it was isoosmotic. It stays relatively isoosmotic. Okay, so that means your dilution is fixed. It can't dilute it, can't concentrate. So say you have somebody who's on direct Expert has chronic kidney disease. Same thing Let's say they have a. They have 900 million oz, molds of intake, and the maximum dilution they've got is we said 300. That means the maximum they can urinate is three liters a day of, uh, of getting rid of selling things. If you add thirst to that. That means you're gonna have not hypernatremia because you can't get rid of them. So I drink five liters. Two of those leaders stay on board, and that's going to reduce my sodium. Okay, so one left, and this is something I have to emphasize because I don't know what it is, but a lot of the young doctors that were standing me patient's not just the young ones, um, intensive care with very low sodium's. The first thing they would say is it must be s idea. It's like I remember this this constant, this idea therefore everything's s, uh, idea. Until proven otherwise, it's actually quite the opposite. SIA d means the syndrome of inappropriate anti diuretic coma. So basically, you are not maximally diluting your urine because you've got a you're hyponatremic. You could be. You could get rid of that extra water and you're not you're not maximum diluting. And our tray really Perhaps we have decided that if your urine osmolality is not is greater than 100 million Oz moles, then that means you're not maximally diluting your urine. That means you may, you may have s i d. And it's most importantly, it's a diagnosis of exclusion. So what that means is you've got to exclude all those other causes you see on the left hand side of that algorithm. And then you can say it's s I D. And I won't go into all the causes of S i. D. There are numerous things like, uh, various infections, like tuberculosis or intercerebral. Uh, tumor's, uh there are loads and loads of causes, and I won't go into them. You can look them up in the books HIV. There are lots of cost, but it's not the first thing you can be thinking of. You have to exclude everything else first. So don't just go down that line of least resistance and say it's easy OS idea because that's what happens all the time. So what about diagnosis and treatment now? Well, here's your overall picture of what are the causes and possible causes of a low sodium so hyponatremia don't forget. It's a water problem. Too much water. We have to get rid of that water, and often there are multiple causes, so you may have somebody on diuretics. Commonly, it's thiazide diuretics. We don't know why thiazide more often than frusemide, but it's commonly thiazide. You may have a low solute intake. You're not very hungry because you're ill. You're in heart failure, so you're effective. Arterial blood volume is a bit low, so your body's reacting as if it's, um, uh, it's, uh, it's hypovolemic. It's it's perceives. Quote unquote, that your effective arterial blood line is low. You may have a renal impairment, uh, etcetera, etcetera, so often multiple causes. So here's a question for you, and I won't expect you to answer this, but just bear this in mind. What are your priorities when treating hypernatremia? Now there are really is only one question you want to ask yourself, and I see so often do people. People would send me patient's, and they would not answer this question correctly. So if you remember only one thing from this lecture today, just remember this next slide when you use them. I couldn't drink it. I want to ask one question. Are they symptomatic? So do they have neurological symptoms or are they a symptomatic? And that's important? Why? Because if they're symptomatic, you have a medical emergency on your hands and you've got to treat them aggressively to prevent cerebral edema. Now, I won't go into the details of how they treat this, but essentially, you give hypertonic, saline or even mannitol to try and shrink the brain because your brain maybe swelling because you've got, uh, this acute hyponatremia. So water on the outside of the cerebral cells gets attracted inside the cells cause they're they've got a higher concentration of salute, and so they swell. And if you get the swelling of your brain, you can get, uh, neurological symptoms. And that's really important if the person is not symptomatic. So you have a low sodium and they're a symptomatic. Then you don't have to be aggressive. In fact, you should not be aggressive. You must go slow. And when I say slow, that means you want to slowly correct their sodium by by about the order of magnitudes. About 10 million as Mel's. Um, sorry. Millimoles Millie Osmo. Sorry. No million miles, million miles of sodium per day. Okay, because if you don't, you might get we used to call Central pontine myelinolysis. We don't call it that anymore because it's not just, um, located to the ponds in the brain stem. It's osmotic demyelination syndrome or some people call it O D. For sure. So you ask yourself if someone calls you up and says, I got a bad case of hyponatremia? You say? Okay, I got one question for you. Are they symptomatic or they're symptomatic. So are they in a coma? Are they convulsing? Do they have focal signs? If they say no, no, they're sitting in bed and they're okay. Okay, fine. Then we're going to correct it slowly, if they say Oh, no, they are Really, um they're they're in a coma. Then you've got to start giving them hypertonic saline to increase the sodium to a degree. And if for some reason that's not the cause of their neurological problems, it's not gonna cause them any harm. Okay, So, symptomatic or asymptomatic, that is the one question you have to ask. So if they're asymptomatic, what are you gonna do? Well, let's go back to our construct. If they have a low a d a. That's appropriate. You want to get rid of that water, you don't. You do not want to add water to your body. So they've been drinking too much pota mania. We call it you want to restrict the flute if they don't have enough intake or tea and toast, you want to feed them if they have a high idea. So that's inappropriate because you're trying to get rid of that water and, uh, and they can cause there's not, uh, there's, uh they're adding water to their body, which is the last thing you want to do. If they're hyponatremic, you may say, Well, maybe they have a volume problem. Hence, volume takes precedent over osmolality, in which case they may have a low, effective arterial blood volume. If that's the case, is it because of a raised extracellular fluid? So it's uncoupled. In other words, they've got congestive cardiac failure, cirrhosis or sepsis, for example. You've got to treat that underlying condition, Easy said, Easier said than done if they have a low extracellular fluid, so they are coupled. So they say they've had diarrhea and vomiting. That case, you want to restore their volume, you want to give them, say crystalloid and lastly Oh yeah, if they're on diuretics or they have chronic kidney disease, you want to stop the diuretics, especially if it's thiazide and you may want to restore their blood volume or restore hormones if they have a problem said with thyroid problems. And lastly, if they have SIADH, then you may want to fluid, restrict, give loop diuretics in this case and treat the underlying condition that causes the SIADH. So, as I said, might be a chest infection, they might be tuberculosis. There are lots and lots and lots of causes, and you might use something called vap tans vap tans, which basically are inhibitors of your aquaporin, which are the doors I was telling you about in the collecting tube. So how do you treat symptomatic? You've got to treat it urgently. It's a medical emergency. It takes precedent over the risks of getting osmotic demolish dating Demomination syndrome. The reason I talk about this now is because I had so many cases in my career where someone's got cerebral edema there in a coma and the medical person selling sending me the patient to I t. You would be saying, uh, we've been going really slow because we're afraid of OD. That's what they're taught, and they don't realize that that's not appropriate. Cerebral edema and neurological symptoms takes precedent over the risks of osmotic demomination syndrome because you don't want to get cerebral edema. That's a medical emergency. So if your symptomatic you've got a medical emergency in your hands, if you're a symptomatic, then you want to go slow. As I said in about 10 million moles of sodium increase per 24 hours, because there is a risk of osmotic devaluation syndrome. So how do these complications work very briefly if you have acute hyponatremia? So we're talking about you know, you know people. By the way, the textbooks will always say divide people up into acute and chronic hyponatremia. And that's that's that doesn't work because someone comes into the accident emergency department with hyponatremia. I don't know when it started. Just because I discovered today doesn't make it acute. So that's why symptomatic and asymptomatic is a much more practical and important way of, uh, of assessing these pick. So how does this actually work? So why suddenly make you hyper Metronic? What happens here is that I lower my sodium outside the cell outside the brain cell that higher, relatively higher osmolality inside the cell attracts water and myself swells story blood. Um oh, on the other hand. If it's chronic, I've had it for a long period of time, and I don't know how long they've had it for. What happens here. Is that you, your yourselves, try to readjust to the new environment that's outside the cell by extruding what they call it the agenda cosmos, the Osmonds. Within the cell, they'll get rid of those osmos. So it's now re re establishing a balance between the inside and outside of the cell. And if I suddenly raise my sodium too quickly, what happens is that now water now is attracted outside the cell. So just like that, over genius or earlier, uh, it shrinks it. And if it's myelin, it causes the damage to the myelin, and it causes all kinds of neurological problems that tend to be quite serious. And that's called osmotic demyelination Center. So the the old, uh, the old textbook description of dividing people into acute and chronic doesn't really work because I don't know if it's acute or chronic, but I do know if it's symptomatic or asymptomatic. And so the lab approved. How do you approach these people when you see them on the ward, for example, well, you've got two questions to ask yourself. Are the kidneys able to concentrate? And secondly, is the patient perceived to be hypovolemic? Because that's that. That's why you're trying to save this water despite being hyponatremic, which is, as we said, it takes precedent over high volume. Takes precedent over osmolality. So those are the two questions you wanna ask yourself. Can I can my kidneys concentrate? And is my patient perceived to be hypovolemic maybe, and maybe just a perception like they have cirrhosis. Okay, so how do I tell if I can concentrate? You look at the urine osmolality, because if the urine osmolality is less than 100 that means you're you're diluting your urine. So everything's working as it should because you're trying to get rid of that extra water so your urine will be dilutes will be like, you know, almost looks like water. Sometimes you're drinking a lot. On the other hand, if it's over 100 millions most per kilo now, we said 50 earlier, But again, um, various learned bodies say 100 is the threshold. Uh, if it's over 100 million as most per kilo, you're not maximally diluting. Okay? so everything is not working as it should. You're not maximally diluting the urine. So you want to look at the urine osmolality. The second question you asked is this is the patient perceived to be hypovolemic. They may not be really high public, but your body thinks their hip of a link because remember, it was engineered. Two was never engineered to, um to deal with cirrhosis or liver or cardiac failure. They didn't have that problem 11,000 years ago. And there you look at the urinary sodium because remember, we said that the Rast system, angiotensin two, will save sodium. So you it'll save sodium. So you're in really poor and sodium. So if your sodium is less than 30 millimoles per liter, you're probably gonna be, uh we can say you're probably, uh you've probably got a low, effective arterial blood volume, so you're gonna produce salt poor, concentrated urine, and that could be either uncoupled. So you have made, you know, cirrhosis and sepsis and heart failure, or it can be coupled. So you had diarrhea and vomiting, for example, so you've lost a lot of a lot of fluid, so you truly do have a low arterial blood fine. Or if it's more than 30 million millimoles per liter, you don't have a low, effective arterial blood volume. But maybe your your kidneys can't retain the song. Why? Because you're in congestive cardiac failure in, um, you've got a fixed dilution because you're on diuretics or because you have chronic kidney disease. And lastly, if you have more than 30 you're not retaining Um uh, sodium. And you have a urine osmolality greater than 100 and you've excluded all the other causes. You may have this idea, and it's a diagnosis of exclusion, so it's not the first thing you think of. It's the last thing if you like. So let's go back to our initial clinical case. We talked about the old lady in the ward who had pulmonary edema from cardiac failure and oliguria and was breathless. Her sodium was a little bit low. Nothing too dramatic. We treated her correctly. She had a good effect. Four days later, she looks better, but per sodium is low. Why? And what are your treatment priorities? Well, why? Why would you be like that? There are lots of reasons. So, um, he had a low saloon take. She's on a tea and toast diet. So let's say if he's taking in 250 millions miles per day and let's see her urine. Osmolality is 2 48 because she's on diuretics. She can't really alter her urine. Osmolality, therefore to 50 divided by 2 48. It's close to 2 50 equals the maximum you can get rid of is one liter of water clearance a day. That's it. But he's thirsty, and we said he has a fixed dilution because of diuretics. He's thirsty, so he's gonna drink more than a leader. He's on diuretics. He has a fixed dilution he can't dilute, nor neither concentrate her urine. And she has a low G f R because she has heart failure. She may have a degree of cardiorenal syndrome so she can't produce the filtrate that can be modified. But even if she could, the diabetics will stop her from modifying that filtrate. And you may have a low effective circulating a low, effective arterial blood volume secondary to heart failure. So these are all reasons that would cause her to be, uh, in a situation where she will lower her serum Sodi And what our treatment priorities? Well, if he's symptomatic, no, she's a symptomatic. Therefore, we want to slowly raise your sodium by the order of 10 10 million miles a day so we don't have to rush in with the hypertonic saline. Okay, so to recap all this, there's a lot in it. It's worth thinking about this because if you understand this once, you can go through the rest of your career without having to go back and back and back to textbooks. So first, the rules of the game sodium determines your volume status. Water determines your tennis itty your osmolality. You've got to take into account someone's saw you intake because you can't people your water so you don't have the solute. You can't get rid of that water. People that are sick are thirsty. They're not hungry, so they won't take the salute in. But they will drink. You got. Remember how the nephron works. You've got to deliver filtrate. So if you don't have glomerular filtration, you're not gonna be able to, uh, modify the filtrate. You've got to have the diluting segments that works. So if you're on diuretics, for example uh, that's not gonna That's not going to be able to, uh, allow you to adjust. And lastly, you got to have, um, uh, anti diuretic hormone that's you have to low anti diuretic hormone because you don't want to add water to your body when you're already hyper to treatment. You got to remember the concept of effective arterial blood volume because your body may think it's actually hypovolemic when it's not with thanks to modern illnesses. So you want to look at the urinary sodium. If it's low, that means you're trying to. Your body thinks it's hypovolemic. It's trying to retain salt and water, which is what it's supposed to do. Uh, this is something where you miss down and leave that, and these are just the algorithms we talked about. Remember, we said they're often multiple causes in this sort of map of what can happen that will cause you to be hyponatremic. It's not common that there's only one thing, and we approach it in someone who's a symptomatic. You want to look at the urine osmolality, and you want to look at the urinary sodium, see if they can concentrate or dilute and to see if they are perceived to be hypovolemic or not. And remember, this is the most important slide. If someone comes in with severe hyponatremia, you want to ask one question. Not Are they acute or chronic? You want to know? Are they symptomatic? In which case, it's a medical emergency. Got to treat them aggressively with hypertonic saline or mannitol. If they're not, you want to go slowly. 10 million miles a day of sodium increase because you don't want to get osmotic demyelination. Uh, is that that's all I have to say. Is there any questions? I'll be happy to take it. Okay, um thank you very much, Doctor Vogel. There's no questions currently in the chance. If anyone wants to write questions now, So who am I talking to you now? Uh, sorry. This is Hannah. Austin had to leave. There were technical issues. Uh, so that was clear to everybody, Was it? There are no questions, so hopefully Okay. Well, do you have questions? I'll be here for a few more minutes. Um, in the meantime, um, could everyone please do the feedback form? Uh, and write any additional comments you have in the chat? Uh, and then right at the end, I'll post the certificate. Also put now in the chat the link for the next lecture. Oh, there's a question here. Um, please explain the effect of hyper or hyper n a on the brain. Yeah. Can I go back to my slides briefly. You should be able to Yeah. Okay. Um, yeah, it's good. Uh, okay, So we said that if you were to if you were to, um rapidly lower your serum sodium means you're lowering your osmolality. Rapidly, quickly. Acutely. There's your brain cell. It's got oz mold. So it's got its own osmolality inside the cell and outside the cell, you have osmolality, which is in the form of sodium and water. Inside the cell, you have Osmonds and water, and if you quickly lower the sodium, then that means it's less. It's less concentrated as hypotonic, and so water will be attracted into the cell. And so the cell will swell, which means you'll get cerebral edema. If it's chronic hyponatremia and your your brain is adjusting to the new environment outside, it will get rid of some of those Oz molds. Okay, It takes time. Takes about 24 to 48 to 72 hours, but the new environment will be in the cell will be altered, so we'll get rid of Oz moles. If you now suddenly increase the sodium. It's a bit like that. Oh, burgeon the the the You know the eggplant that you saw in the very beginning that'll attract water outside of the cell. And that will shrink your your your myelin, your your your your neurological tissue, and you'll get what they called osmotic demomination syndrome. So in the textbooks, they talk about dividing people up into acute or chronic. But the problem with that is, is that you don't know if something's acute or chronic when you see the person you can't tell. Just because you discover it today doesn't mean it's a cute, and so it's much more informative if you divide the patient's up into symptomatic or asymptomatic. Okay, is that is that clear? There's no response in the chat, but oh, yes. Okay. Uh, we do have a few more questions. Unfortunately, we've got a lecture coming up in two minutes, so I don't think there's enough time, but thank you very much. Okay, Well, if you want to send me the questions. A later date. I'll be happy to, uh, I'll take a photo of it now and I'll put it on the WhatsApp group. Okay, great. Thank you. Thank you very much. Thank you. Everyone, please do the feedback form in the last. We've got 12 minutes left and the next lecture is starting in two minutes. The link is in the channel, so thank you very much, okay?