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Okay. Hello there. Um, as I've repeatedly said, my name is Doctor John Bogle. I'm a recently retired intensive care consultant, anaesthetic consultant in the NHS. And I'm trying to explain some of the basic physiological principles that are often misunderstood, poorly taught, but very, very useful in the clinical arena. So it's important that you understand these and that you you find them, you might find them enjoyable. Okay, so let's see if I can, uh, share my screen here. And here we go. Okay. So, um, just want to get rid of this hype like, uh, yeah, Okay, so last, uh, last week, we talked about, um uh, acid base and acute medicine, and I went through some of the more traditional ways of understanding explained not understanding explaining acid base, the kind of things you see in most textbooks. The problem with those techniques is they are inadequate. They don't explain. They don't help you. They don't always help you in therapy. Because if you don't understand the mechanisms in more complex cases, you can't really use the appropriate therapy. So the technique that's being used more and more by people that deal with complex acid based problems endocrinologist, nephrologist, intensive care doctors and the like, Um, is something called the Stewarts method. It's a named after Peter Stewart, who recently passed away, is a Canadian biochemist physiologist, in fact, and, um, his is a, um, a mechanistic approach that uses a lot of maths. Now the problem is, most people I know and that's myself included, are not very, um, proficient at maths. So as soon as I see a polynomial equation, my eyes glaze over. So with a lot of help from friends who are chemists, I put together this talk that tries to explain Stewart's method without using mass. So you have to bear with me. I'm going to simplify this so you could pick me apart if you wanted to. But if you're a pure chemist, but it does work, and it does work in the clinical arena, Okay, so we're going to go through how Stewart's physical chemical method works, and we're going to use, um, not maths. We're gonna not gonna use it mass, and I'll give you some clinical examples which will make this more relevant to you. Okay, So for Stewart's physical chemical approach, you have to understand some very, very basic principles. And what he does is, he explains, the, um the physical chemistry of the most important element in the extracellular fluid, which is what we're dealing with, which is pure water. And then we look at outside influences on the dissociation of pure water. So this may take you back to your high school chemistry. But that's okay. You're gonna need to understand this and you'll see the relevance clinically. Then you're going to add what we call strong ions, ions that totally dissociated. Then you're gonna add week ions, week ions, Orions that only partially dissociate strong iron. So if you put in sodium chloride, for example, I told you last time you're making spaghetti and you throw a handful of so 5 g of sodium chloride salt into this water to make your spaghetti. There's no salt in the water because n a C L becomes an A plus C l minus all of it. If you have a week, I on like a bee and you throw the same Abyan water. There'll be some a plus. There'll be some B minus and will be some. Maybe it doesn't totally dissociate Now we're gonna add C +02, which becomes a weak acid as well. Bicarbonate, bicarbonate, carbonic acid. And we're gonna use sound deductive reasoning. I crossed out the mathematical cause. The whole goal of this talk is to try and help you understand this. Uh, it's a real It's a real advantage, but without using the mass. So before we get started, let's get a better perspective on acid base. So if we take, um, a leader of plasma and you compare the various elements that we're going to discuss today, you're gonna see how they compare in terms of orders of magnitude of quantity. So to make this simpler, I'm going to use an analogy a bit like in the old days. If I went around Europe and I want to look at the cost of a Volkswagen Golf, let's say I'd have to go to France. I'd see in French francs Germany would be Deutschmarks Hollywood guilders. Italy would be millions of flare, of course, and now we have a common denominators, the euro. So we go around Europe, we can see the same car and we can compare the price is much more easily So what? We're going to do now is we're gonna do the same thing with the various quantities and the way we quantify these elements. So a leader of plasma will contain 49 animals. So animals are going to be no animals per liter. It's going to be our our euro if you like. And if you have a pH of 7.4, remember, I said it was a negative logarithms. So the higher the number, the less eight plus you have the more o h. You have so 7.4 is 40 animals. 7.0 is 100 animals. Okay, so you have 40 animals of hydrogen ions. You have a ph of 7.4 in plasma in a liter of plasma. If you have a leader of plasma, you'll have 100 and 40 million moles. That's 100 and 40 million, Nana Mel's because we're using the same denominator here the same, uh, same currency if you like. So you have obviously a lot more sodium than you. Hydrogen. It's And this is 11, number that you probably don't know in water. You're gonna have 55 billion animals of water, so you can see We've gone from 55 billion animals of water, 2 40 animals of hydrogen ions, which is what our pH is about so you can see the biological impact is, Stewart said of H Plus is out of all proportion to its magnitude. We're talking orders of magnitude difference. Okay, so a couple of fundamental principles that you have to understand if you're going to understand the the the explanation of how Stewart's model of acid base balance in acute medicine works. So the first, the first principle is the conservation of mass. What does that mean? It means that the sum total of substance in an adequate solution has to be a constant. So in the case of water eight plus times O. H. Minus, So it's a product is a constant, but that means is that if one goes up, the other one has to go down equivalent because it's a constant and the other, uh, principle is electoral neutrality. What that means is that in the aqueous solution, you have to have the same number of negative negative and positive charges. If you didn't, you'd be a battery unless you can glow in the dark, you're going to have the same number of positive negative charges. So those two fundamental principles are absolutely essential to understanding how how Stewart's works. Conservation of Mass Uh, so the product of H Plus and O H minus is a constant. So one goes up, one goes down. If they both are out equal, that's fine. But if one goes up out of an outside influence, that, uh, drives it back into two solution, then the other one has to go down. So it's like a seesaw, and the other one is electrical neutrality, equal parts of positive and negative cartage. You have to understand those two so all acid based states result, according to Stewart, from Water, and it's dissociation that's really important to understand. So we said, water becomes H plus and minus. And because of the dissociation of any, uh, any compound is going to be determined the quantity of dissociation. It's gonna be determined by its, uh, dissociation coefficient. We call this K W. Now. We just said that there are no leader of plasma. We have 55 billion molecule of animals of water, and we have 49 animals of H plus, So the constant is essentially the K w. The dissociation coefficient. Sorry. Association coefficient is a constant. What? What? What do I mean by that? I mean that if you were to suddenly make my dissociation coefficient a million times bigger, that would change the amount of H plus that will be dissociating from H +20. Don't forget we're going from 55 billion to 40. Um, it would increase it by 0.9%. So almost nothing. So I can make it a billion a million times bigger, 10 million times more. And it essentially won't change the amount of H plus relative to water. So you could say that this is a constant. So the constant will equals each plus times at which minus, so as we said before, because it's a constant. If one goes up, the other one has to go down to maintain that constant. Let's see, um, conservation of mass principal because we have to have an electoral neutrality. In this case, you're gonna have a balance if you have water and it associates a very, very, very small amount of it associates it to 49 Amal's of H plus But that also means 40 animals of age minus. Then you're gonna be in balance. But if anything from the outside influences, uh, the the solution you're using, then you're gonna alter the balance of H plus No. H minus one goes up, one goes down. And it's these independent variables, according to Stuart, that control acid base by influencing water association. If you find this a bit theoretical, hold on because we'll come to some clinical cases and you'll see where this is really useful. So we're going to start by making a soup now. The problem is, as I said, there are 55 billion animals of water and there are 49 animals of H plus. So if I were to draw this to scale, I'd have a tower that would be out into the stratosphere. And I have a, uh, a membrane that would equival that would be equivalent to the H plus. So the the massive column would be water, and the membrane would be H plus. Now I can't draw this on my computer, so you're going to have to use your imagine age. So let's say we have a We'll start with a column of water Okay, and the water dissociates to a very, very small degree. Don't forget 55 billion to 40. And there that's your equation. So the positive column Positive Charge column is going to be with water massively high again. This is not drawn to scale, obviously, so the negative column is going to be equal. And because you have neutrality, H Plus has to equal O. H minus. There's your H plus column, and there's your H. Once again, I can't emphasize this enough. This is not drawn to scale. You have to use your imagination. If you want to avoid maths, that is okay. And so we're in total balance. Now let's take. We're going to continually build on this idea of these columns. These what they call gamble columns after a doctor gamble. So there's a positive column. There's a negative column with water lots and lots of water. We're gonna add salt, so the Salt Associates, totally to N A plus and C L minus were in electrical neutrality and a very, very small amount of water associates into H plus n O H minus. Remember the proportions. We have 55 billion water 440 million of any plus and C l minus and 40 hydrogen and then 40 of O. H because we're in balanced, So everything is in balance so far. Now, things get interesting now because in biological fluids, and this has to do with membrane stability and Oz modality. Um, for some reason we have we always have more positive than we have negative, strong ions. So let's look at our column again. We're gonna build this up. We're gonna call this a soup if you like. We're gonna build this soup. So there's a positive negative call. We're gonna add our plus of sodium plus. But this time we're not gonna have the equivalent amount of chloride, the negative strong iron. There's your age. Plus so where there's a difference from the sodium and chloride, and that difference is very important and the term we use and it's a very important term, which you're going to hear over and over again. Today is what we call the strong ion difference. Now that strong iron difference is the difference between the positive strong ions and the negative strong ions. And for the moment, we're going to build on this. But, um, there's a big gap. They're now you're gonna have to fill that space because otherwise you won't have electrical neutrality. So for the moment, what is going to fill that space? A way to minus. So our balance is gonna tilt way over the O. H. Now, if you remember in the first lecture, we gave a very simple definition of an acid and a base. And acid is a solution where there's more H plus and O H minus and a bass is a solution where there's more O H minus than h plus. So for the moment, we've got ourselves an alkaline solution, a base. And if you recall that the normal ph is 7.4. So when we say someone has an acidy me a an acidosis, you'll hear people say What we're basically saying is your reference 0.7 point four, which is quite alkaline. So even if I'm 7.1, you say always very acidotic. In fact, you're still alcoholic, uh, in terms of, uh, in terms of, uh uh, the biochemistry. Now I'm going to use an analogy to make this a little bit simple, and I do apologize that this is, uh, insulting to some of you. But I find these analogies work. This strong line difference. Imagine I have a house and I have just bought a house and have a new attic. And I have this attic that's big The size of the attic. Is this strong line difference? So how big it is depends on the strong iron difference. Now, I have a lot of books, so that space in my attic is always going to be full to the to the to the maximum. So for the moment, I have that space. Besides, that space is defined by the strong wind difference, and so far, I can come in and put my books in there. But as you'll see, other people in my family will come in and put their things in, which can leave less space for me. Okay, so let's carry on. Uh, I got to get rid of this. Keeps looking. So the strong and difference. So let's look at the strong difference. Normally, it's about 40. Some people say 42. It depends on your lab. But just to keep things simple, let's just say 40 Okay? So we're saying sodium depends on the lab again, but let's keep it simple. Your normal sodium will say, is 100 and 40 million moles per liter, and your normal chloride is 400 millimoles per liter. I'm not going to bring in my magnesium and potassium trying to make this simple. So 40 difference between 100 and 40 of sodium and 100 for chloride. So it's a difference of 40. That would be the normal. What would decrease the strong iron difference? That would be things like some people call a hyperchloremia acidosis. So I give someone large volumes of saline. Now, why would it do that? Because again, going back to the analogy, If the size of my attic is small earlier, then I have got less space to put my things in it. In other words, there's less space for the oh eight. And so the balance goes from extreme, uh, preponderance of O. H to less space Freud. So you're getting less alcoholic or you call so you could even say acidotic. So it's the size of your attic that will, you know, will allow you to put in your your books in my case. Okay, What if you make your strong and difference bigger? So, for example, if someone has diarrhea where you have a gastric tube and you're sucking out all this acid from their stomach or you have diuretics, you have a diuretic like frusemide. You tend to lose, um, two chloride ions for every sodium mine. And so in that case, you're strong. I difference because it's it's the difference of sodium to chloride. The strong difference gets bigger because you have less chloride compared to relative to sodium. So what happens is you have more space. That space has to be full. You can't. Otherwise you won't have electrical neutrality. So what fills the space? What comes out of solution? Oh, eight. So you're becoming more alcoholic. So someone who's got diuretics over a period of time, you may well see them being alcoholic or someone who has diarrhea or someone who has a gastric tube in. And they're sucking out a lot of fluid. That's acid. You're gonna you're gonna reduce the strong wind difference, and you're gonna create more space for it and your alkaline tick just to quickly show you if you don't believe what I'm saying, Here's a leader of extracellular fluid, and that's the 1 40 of sodium chloride, 100 and strong and difference of 40. We just said, if you mix it with an equal volume of saline and saline, normal saline 0.9% normal saline, the one we use usually is got a strong iron difference of zero. There's an equal amounts of sodium deployed. Subtract one from the other. There's no strong iron difference, so if you mix those two beakers together, you can do the arithmetic. You'll have a strong iron difference of 20. In fact, if you were to use a lot of pure water, you will get exactly the same effect because you're going to dilute the strong iron difference of extracellular fluid. So both of these examples, in fact, you're reducing a strong iron difference to your attic is smaller. You have less space for my books or oh, it. Hence you become less alcoholic, more acidotic, and they call this a hyperchloremia acidosis. But if you're a purist, it's not a hyperchloremia acidosis. It's a strong mind difference acidosis because you get the same with half normal saline quarter normal saline water anything that doesn't have a strong and difference of 40 you're going to get a reduction of your strong mind difference. And you're going to get, uh, an acidosis because there's less space for like and what affects it. Well, sodium bicarbonate. So how does sodium bicarbonate work if I give you sodium bicarbonate any HCO three minus the bicarbonate eventually becomes water and CO2. And what happens to the CEO to you? Breathe it out. So you're left with sodium, which is unaccompanied by a strong negative ion. Sorry to interrupt, Doctor. I think someone has a question. Someone's raised their hand. Yeah, go ahead. Hi there. Yes. Sorry. Regarding the last point that you made regarding the hypokalemic acidosis. That's something I've always wondered how obviously arising Chlorides, obviously being negatively charged causes this and I think you you kind of obviously you alluded to it. Or you you basically said how this reduction is strong. Iron difference is what causes it because so I I really understand. I don't Yeah. How How How does how is that working? Sorry. How is this? How is this negatively charged Ion Causing this? So I tried to explain the beginning is there are many ways of little absent base. And the when you first came into this talk, maybe last week, I asked you to sort of take, like, a blackboard, erase everything and start fresh. So I'm trying to get you to think in terms of the way Stuart thinks using a physical chemical method. And so you're gonna have to follow that logic to understand where we're going. If you hold your fire for a little while, I'm gonna give you a lot of clinical examples that may just make this clear. And if you're still not clear, then we can talk about Okay. Oh, thank you. Okay, so if you give sodium bicarbonate, you're basically just giving sodium because the bicarbonate disappears is CO2 that you breathe out. So you've increased the strong iron difference. The chloride doesn't change. The negative ions don't change, but the positive ones do so the strong and difference gets bigger. You got to fill that space with something that will be, oh, eight. So you become more alcoholic. So this is a true story. One day I had a colleague of mine who was in intensive care he had an asthmatic patient who was extremely asthmatic. He was very tight. He had to intubate him. And of course he was giving him all the Broncho dilators, which is the treatment of choice. And And the problem was, and this is the problem with asthma is you can't get the gas out of somebody's not not get the problem isn't getting ox cream into them? It's getting the gas out. In other words, getting CO2 out and one of the things that kills you with asthma, in fact, is hyperinflation. So you either cause right heart failure because you're right heart, which isn't a very good pressure generator. Unlike the Left heart, can't get blood through those very distended Alvey oil, which you're crushing capillaries. Or you may get a tension pneumothorax if one of those alveola that are like balloons that are bursting pop and you get this pneumothorax so the problem is getting the gas out. The only way you can do that is to basically use Broncho dilators, but in this case, it was taking a while for them to work. So he was getting more and more retention of CO2 because he couldn't get the gas out. And so, as we said, Broncho dilators are the treatment. I'm not contesting this, and by the way, I'm not going to be telling you how to treat asthma in this example. But it's just to illustrate the acid base side effect. So, um, this is the gas that my colleague saw when he, um when he was dealing with this patient. So you can see that there's a severe uh Ph. Ph is 6.75, so it's very, very low. The CO2 is very high. Normal is 5.3. Basic cess is okay. So it's not a metabolic problem. It's purely respiratory. So would you correct the pH with bicarbonate? Well, not okay, Good. Well, he did. And what happened? Well, he gave 200 mils of sodium bicarbonate. As we just said, the sodium will be retained so you'll increase your strong iron difference. You'll create a metabolic alkalosis. But what becomes bicarbonate? It's CO2. What's this man's problem? He can't get rid of CO2. So he's got a hell of a load on his shoulders and he can't. He's just making it worse. And so he gets this result back. So, yes, his Ph got a little bit better because he's got he's created a slight, um, metabolic alkalosis slight. But his CO2 is un recordable because it's so high now and his bicarbonate un recordable. So he's made things a lot worse. So he asked me to come and give him a hand, because for some reason, he thinks I'm, uh, an acid based guru. And I'm not, um So what? So what I did? And again, I'm not saying this in a million years. This is the treatment for asthma. I'm just trying to buy time. And I was trying to illustrate a principle here. I put him on a freeze mud infusion. Now, why did I do that? Because frusemide will remove your your chloride. It'll create a metabolic alkalosis. So it's doing the same as bicarbonate without creating the CO2 and over time and again. I'm not saying this. This is just bought time. Eventually, his metabolic side got better, and eventually his po two came down. That was the bronchodilators, not the frusemide. So I'm just I'm just using this to illustrate this point, I'm not trying to tell you to use frusemide for asthma. So what about the next thing we're going to add to our soup? Okay, we're gonna add a weak acid now, the week acid we use most of the time. The one we talk about is albumin, phosphate as well. But album is by far the most important quantitatively, unless you have acute renal failure. So let's stay simple. And let's just stay with album. Albumin is a weak acid, so it doesn't totally disassociate partially. So let's go back to our soup. Positive charges. There's your column of positive ions theirs euh Plus there's a negative we have are all important strong iron difference. So we've defined the size of the attic, how much we can put into it. And I said, I want to put my books in there. Okay, But now my wife comes along and she's a painter. She wants to put her paintings, so we're gonna have to share this space now. So we define how big is the attic? That's a strong line difference. That's key. Now my wife is gonna put her paintings in there, and she's taking up my space with her album in Okay, her paintings. So there's gonna be less space for my books so that oh, eight, which was what I was saying, We're my books is going to be less, um, impressive than it was before. He's taking up some of the space. So the balance that was tilted way over to the wage is still gonna be tilted, but not quite as much. So you see, we're seeing define the size of the space, the attic, and then we're gonna start filling with various things. And that's going to be how Stewart's going to explain how things work. And now we're gonna add CO2. That's another element that's important in our construction of this soup. Okay, there's a positive column. Again, again, this is not drawn to scale. Obviously there's your age. Plus, there's your negative. There's the space. We've already got our album, and that's my wife's paintings. And now my son comes along and he's got his his guitars. Okay, he's a musician, so CO2, as you know, is in equilibrium with H plus and bicarbonate. So the the you have C +02, which becomes bicarbonate and vice versa. So guess what with the CO2, whatever that happens to be, you're gonna get an equivalent amount of bicarbonate, and that bicarbonate is gonna be taking up space. That's my son's guitars. Okay, so the space we've defined as the, uh, as the, uh, attic, that's the strong iron difference. And now I had all that space to myself. Now I have to share with my wife's, uh, paintings. That's the albumin and my son's guitars. And that's, uh, c 03 minus, which is a reflection of the CO2. And so now there's even less space for my my books. Okay, so the balance, which was initially very, very much in the O. H minus favor the words my my books is there's less space for me now. There's some space more than eight plus, but less than it was right in the beginning. And when you look at this, it's quite interesting, because if I suddenly get well, I'll come on to the next thing in a second, you'll see what I'm going to say. So let's say you add Lac tape, Okay? Someone has a lactic acidosis is someone's got sepsis. and they suddenly have this, you know, Lactated. General five. Let's say so. Here you're positive charges again and negative. There's this black Tate, so lactate is a strong eye on. So when I said the strong negative ions were mainly chloride, it also is lactate if there's an excessive lactate. So we've in this case we have a strong iron that's chloride and lactate. And so now a strong I'd difference is going to be smaller because lactate is a strong iron. And there's my wife's paintings with A We call that album in and the c O H. C 03, which is the, uh, the reflection of the CO2. And there's even less space for Ohh. So I've got even less space for me because the lactate you want to think of it this way occupies. It makes that addicts smaller because it's a strong iron, unlike the others, which are not strong irons. And so there's less space now because the attic is smaller for bicarbonate and O H minus and lot tends to stay pretty much stable. And, um, and so when you think about it, if someone has high lactate initially, what will happen is they'll start hyperventilating to blow off. To compensate for that. That's a respiratory compensation. And so what happens is that the CO2 goes down, and if the CO2 goes down, the bicarbonate goes down. So they're trying to fight for a little bit more space for O H. Minus. So that's why you why you compensate? Okay, And what about a reduced? This is just to replace. Repeat what we just said a second ago. If I give saline, for example, there's there's there's no strong iron difference and saline. If I give enough saline, I'm going to dilute my strong iron difference. So this I hope it answers to your question to a degree. So there's what I start with. There's my space besides my attic, and they're all the elements that are filling my attic. And if I give, say, a lot of saline, what happens? I've increased the quantity of chloride relative to to sodium. It's not an absolute terms its relative to it. So the difference my strong and difference is going to be smaller, so there's less space per album in There's less space, um, for album and bicarbonate and O H minus. So again, these are squeezing bicarbonate and O H minus out of that space because the the attic is smaller. Okay, so what we've just said is, in fact, everything is going to that's going to influence acid base is going to be, um, the influence on the dissociation of water water is the big big player, 55 billion animals compared to 40 animals. I'm sorry to repeat that over and over again, but it's really important to to get a feeling of the the the quantities were talking about. So what are the three independent variables we use to make up our acid based, um uh, acid based, uh, profile? One is a strong iron difference. The difference between the positive and negative strong iron. You know, the iron is totally associated. Essentially, we're talking about sodium and chloride, and if there's lactate lactate as well next, the week ions essentially were talking about album and then lastly, CO2, which is is a week iron because it becomes carbonic acid and, um and that's an equilibrium which bicarbonate everything else. And this is sometimes very hard for you to get your head around, because if you go back to your old way of thinking, everything else is dependent on those three elements and how they influence the Association of Water. So P h plus bicarbonate? They're not. They're markers. They're not the actors. They're not the things that influence is there the results of Of Kangas to those three, um, independent variables. So it's a It's a different way of thinking now to calculate. Calculate Stewart's method and this is why it's not become overly popular is because you've got to You've got to solve this, um, this polynomial equation, But you could do with the computer. There are computer programs that does this for you, or you can use a simplified method. And this is the method I like. And it's a very practical way of, of, of, of deriving Stewart at the bedside. Now, again, Um, it's this is simplified, but it really does work for complex problems. I would not use this for every acid based problem that I come across, uh, I'd use the traditional methods that you saw last week Davenport diagram or basic cess based deficit. But for the really complex cases, we'll give a couple of examples. Stewart's is a very good technique, and this is a very good, simplified way of using Stuart. So what you do is you have to determine for variables. It's not as complicated as it sounds. First, you have to know what the base excess is. You get that from your blood gas make. That's a composite number. As we said last time, you can have a basic cess. It's absolutely normal and have posit, you know, Acidifying influences an alkaline epic. Influence it. As I said last time. It's like having a foot boiling water and a foot in freezing water, and on average, you're okay. Your temperature is fine, but in fact you're not. So the basics s is kind of like the the sum total of all the different aspects. Then you're going to take your strong iron difference or what they call the sodium chloride effect. So we just said, Sodium will say is 100 chlorides. Sorry, sodium is 100 and 40 chloride's 100 depends on your lab, of course, but this is just to simplify it, and so it could be a strong difference in about 40 so I will take 40 away from the results of what I actually have. So if I have 100 and 40 minus 100 that's 40 minus 40. There's no influence, so my strong and difference is absolutely normal. Okay, you'll see what examples in a second now. Albumin is not a strong iron. It's a week on. It's only partially dissociated, so only about a quarter of it associates. So you take your normal value, which is about 42 depending on the lab again. But for simplicity, Staple, say, 42 whatever your albumin is. So let's say my album was 22. That means 42 minus 22 is 20 and I take a quarter of 20. And that will be the album in effect and then lactate. Now there is lactate in your blood. Thank God, because you need it. It's a very, very important molecule. It's what they call lactose or mon. It's got multiple multiple effects. It's also incredibly important fuel. You can't live without lactate, so there's lactate. So if you have one which is a normal value, then you take one minus one and zero. There's no effect of lactate. If I have 10, then I take 10 minus, uh, one minus 10. So my lactate effect is nine. So there's 99, moles of millimoles of lactate excessively and that will have an effect on it. And then whatever's leftover, which I can't account for, is your unmeasured ion effect. Okay, So to calculate that you're going to take all your elements and you're gonna subtract one from the other from the other from the other and whatever's left over you can't account for by those different effects Sodium chloride, album and lactate are things that you just haven't measured. So, for example, if I took alcohol, certain alcohols will give you formic acid if I have someone real failure that you have sulfates that we don't usually measure. But they're just they're we don't know what they are. But you know, there's something there that is going to influence this, but we can't account for it. And that's how we're going to use the unmeasured ion effect again. Let's look at the examples and you'll see what I'm talking about. Okay, so let's look at some clinical examples. I think this may clarify to somebody breathing, so this is a patient who was scerotic, who was intubated. These are all through stories, by the way, intubated and transferred from the accident Emergency department because he had abdominal catastrophe and need a laparotomy. So those are the numbers he's got. I won't read them all to you. You can at home. You can look at the the arithmetic, how you derive this. It'll take me too long to go through every step, but you'll you'll see it does make sense. And so there's your standard basic cess. It's minus 12. Don't forget what you said last time to make things really simple. Of course, a negative basic cess is a bass deficit, and vice versa. So a negative basic cess is a is a metabolic acidosis. If it was 12 instead of minus 12, that would be a metabolic alkalosis. Okay, starting starting chloride effect. In this case, it's minus 12 because you can see the difference between 1 33 and 105 is quite small. It's a small, strong line difference. Subtract that from 40 and in fact it's 12. So you've got yourself a very small, strong iron difference. If you have a negative number by the way in front that tends to be an Acidifying effect. If it's a positive number, tends to be an alcoholic effect, but you'll see in a second and we draw this out in columns and you'll makes it much more. Makes it much more easy to understand, or at least to visualize albumin effect. We said. Albumin is an acid, it's a weak acid. And because this person is lacking an album typical of someone with liver failure, they have low albumin. Um, if you have less of your acid, it's more of an algorithmic effect, cause there's less acid the, uh, lactate effect. So his liver is not working, so it's probably could be due to a sepsis, but it could also be because his liver can't metabolize lactate. So whatever reason it is, the lactate is high, so that's a negative effect. It's an Acidifying effect, and we're going to try and figure out what is the unmeasured iron effect, and we're going to, you know, do the following. Subtract one from the other from the other, and we end up with minus one. So this is where it gets much easier to visualize if you draw a line of unity, so the line is a neutral, so there's no acid or alkalinity effect. If you look at the sodium chlorate effect, we just said there's a small, strong and difference, which means it's a city. It's an acidic effect. It's a negative number, so you can see that the small, strong and difference is small. What does that mean? The attic is small. There's not enough room for my books. Oh, it's not enough room for Oh, it's everything is squeezed out. So you've got a small, strong hand difference. What we call the sodium chlorate effect the album and being a a weak acid. There's less of it because of the problem with the liver, So they're gonna have less acid, so that's gonna be an alcoholic effect. So that's gonna sort of, uh, neutralize to some degree the acidic effect of the, uh of the strong and difference. There's lactic acid that's gonna have an acidic effect. There's something in there that not much of it minus one. That's an acidic effects, always unmeasured ions, always acidic, and then your basics s is minus 12. So if you look at this, you can see where you've got problems. You can see that. Maybe, um, we could start using fluids that have, uh, less saline. So there's less. There's a there's a greater strong iron difference not know strong difference, like saline. Maybe we want to give this guy some album that might make it more acid. But you can see there's a problem with albumin and lactic acid. Um, well, I think the only way you can improve lactic acids, give them a new liver or treat sepsis. Okay, this is another story. Again. This is a man who had pancreatitis after being resuscitated with lots of saline. So I think you can probably guess what we're going to see here to a degree. So those are your numbers, and again I won't read them all out. Those are the various effects we talked about. And if you put them all together to determine what the unmeasured iron was, it's minus 7.5. So if you draw this out, you can see we have because of the recess taken with saline, you're going to have a very small, strong iron difference with a strong difference effect, which is quite considerable because there's no strong and difference to saline because the man has acute inflammatory problem. He's got a relatively low albumin, so that's going to have an Alka Munich effect. He's got a little bit of lactate, so that's gonna have a select Acidifying effect. And he's got unmeasured ions. That's quite considerable. And the reason he had that we never really determine what they were. But he had acute kidney injury with his severe, uh, necrotizing pancreatitis. And so he probably had sulfates, or possibly a few mates. Various retained organic acids from the kidneys that weren't working, so we don't know exactly what they were. If he really wanted to find out, I guess we could call her biochemist or chemical pathologist. But basically he had some some lions that were, uh, secondary from the kidney injury, and his basic says was minus 15. It had been worse if he had had a normal album, As you can see because that would have part, it partly neutralizes the acidic effects of the other elements. Uh, this is a case that it was very striking. I'm embarrassed to admit this. So, uh, in 2020 I was involved with a case of a woman who had taken an intentional overdose. A massive overdose of anhydrous caffeine powder. Very deadly subject. Subs substance. So be very careful not talking about coffee. No, I'm talking about an espresso. I'm talking about anhydrous powder that often body builders use. In her case, she did it intentionally to commit suicide. When we were called downstairs, the accident emergency department. She had already had 93 minutes of cardiac arrest. And when we got down there, they you know, they asked me, what should we do? And I said, Well, you know, you stepped. You've been massaging from 93 minutes and the, you know, the answer seemed obvious. We're going to stop. She was 33 years old, by the way. So we they were very, you know, everybody was very upset. The mother was told that she was dead. Anyway, um, when they showed me the blood gasses, her lactate was just under 30 and her Ph was un recordable. It was we don't record below 6.75. So this was, you know, not really compatible with life. Anyway, I recall the lecture I've been to, like, 10 years before, and I had a website and I had written down some various things that were, um, you know, possible treatment in really ultra extreme cases. This is experimental. And, uh and this is from a professor of Minnesota that I've met, and he suggested using very, very high doses of insulin. And we're talking about not a unit per hour or two units per hour that you give someone who's having a diabetic Keto acidosis. We're talking about 7700 and 50 units an hour. 1000 units an hour. We're talking about mega doses now. I don't want to go into the mechanism, which is not the point of this lecture, but what is was this woman was basically dead, and we tried this out. I asked everybody if they'd be willing to experiment with this. I've never seen it done before. Um uh, a caffeine overdose. It's been done with beta blockers, but not in a positive ionotropic. Uh, substance. So here's what happened. This is a peak is in red, black takes and yellow. Those are normal values. Okay, So the bars gray bars are what normal waves ought to be. This is when the insulin was started. the infusion over 72 hours, her lactate went from just under 30 immediately plummeted to normal. By the way, she immediately started showing signs of waking up and to tell you the story. At the end of the day, she actually survived and went home and wants to become a nurse. Now, ironically, the PA from the other hand did this. It went up from un recordable to a plateau at 72 hours, but it stayed abnormal and I couldn't figure out why. Because the lactate now, which seemed to be the main problem was was seemed to be normal. And we're thinking maybe there's some other element. Maybe it's got sepsis from a gut necrosis because there was no flow to the gut. It turns out that's what one of the problems was, but that didn't explain everything, and I couldn't figure out why. So you can see that the the acid doses got better, but at 72 hours, it still was abnormal. It's not near the gray bar, whereas lactate was normal. Okay, so what happened? Well, I'm embarrassed to say what happened. I know what happened because someone told me what happened, and one of the nurses at the bedside said to me something I hadn't even noticed. This was what her gasses looked like, and this is what we saw when we analyzed it. Using the technique. We just described the sympathized stewards where sodium chlorate effect was massive. He had a very small, strong and difference slight album. In effect, lactate was normal. Now it wasn't when she started. 30 was, You know what we started with. But now it's normal and he's still acidotic. And there was no really unmeasured iron effect. So what was the problem? Well, the nurse brought to my attention something that I'm embarrassed about that because this was a new technique, the pharmacist insisted, who was not used to this, that we use normal saline for every unit or two units of insulin we gave, and we're giving 750 units an hour. So what happened was there's a basic cess that's very acidic. We had given 17 liters of saline over three days, not as not as a fluid to maintain her circulation, but as the the the accompaniment to the to the insulin that we're giving massive doses of insulin. And that's I usually notice in a checklist. I used for one reason because I was so focused on this woman's waking up or not, I didn't Even for once, the only picture I didn't do a checklist on was that. And I would have seen it right away. And I'm embarrassed by that. That was the problem. We gave so much saline to this woman that the reason we couldn't, uh, fix her acidosis, even though we did fix her lactate Axid OSIs was because we were basically substituting lactic acidosis with a strong iron differents acidosis because of so much saline. Well, we just basically filtered her off of that. And she was fine. Went home a couple of about a week later. Okay? Another case. Women came into the ent department found drowsy. A known insulin dependent diabetic. There are her BP and glucose Glasgow coma scale. You can see he's got a high glucose acidotic. He's hyperventilating, and her lactate is high fluids. Insulin are commenced. Now, all the guidelines talk about resuscitating someone with a diabetic ketoacidosis as using saline. That's the guidelines. They all say that. And as treatment was being given over time, ketones were decreasing. So you think the pH would be getting better, wouldn't it? But it wasn't why. Well, I think you can guess. So that's her blood gas. At 13 56 p a tree, it's 7.182. About an hour later, pH is now 7.110. So it's getting worse, not better. And an hour later, again, herpetic is getting worse. 7.0 to 1. So what's going on here? Her ketones are improving. That's the cause of her Keto acidosis, right? Well, maybe not, because you can see your strong mind difference is getting worse. So we graph this out hour by hour. You can see when she came in the unmeasured iron effect. Well, we're assuming that those are ketones. Okay, I'm 99.9% sure there were ketones, and you can see that caused a severe, uh, metabolic acidosis for the basic sets of minus 18. An hour later, her unmeasured ions are getting better come from minus 13 to minus eight. So her ketones are being reduced as you expect. But a strong I difference or sodium chloride effect is getting going from minus two to minus seven, So her basic cess is getting worse, not better. So her ketones are getting her ketoacidosis getting better. But her acid metabolic acidosis is getting worse. And then the last hour, you can see her sodium chloride effect. Her strong indifference is getting really small. Hence there's less space in the attic for awake my books that you like and her unmeasured ions are getting smaller, so the Keto acidosis is improving, But her strong iron difference or sodium chloride acidosis is getting worse. And the thing that's striking about this is the guidelines today still say use saline. In fact, you shouldn't use saline. If you keep an eye on this, you could probably use lactated ringers or plasma like a non, you know, a solution that has a strong iron difference. So did you know we're almost done here? Did you know some interesting facts? There are three organs based on what we just said, based on Stewart's model that control your acid base balance and in order of importance. But we said the elements were CO2. So that's your lungs. You're blowing off a lot of CO2 in a day That's the most important asset based organ based on Stewart's model. Remember, we said, there are three independent variables. One CO2 and that becomes bicarbonate. Second, the kidneys. The kidneys remove klor excess chloride. So if you're small, if you're strong and difference is getting too small, your kidneys will get rid of chloride and re establish the strong wind difference. And, lastly, a liver. Because the liver produces album, which is a one of the three independent variables, Uh, that controls um, Association of Water based on Stewart's model. So there are three organs that are acid based organs. Now the kidney gets rid of strong, Uh, maintains your strong line difference. The extracellular fluid strong line difference By getting rid of chloride and you can't get rid of chloride on its own, you have to keep electrical neutrality to accompany it with so with ammonium. And there's something called renal tubular acidosis. And what that is is you can't your your tubules aren't working. They can't produce ammonium, the positive ion so you can't get rid of the chlorides you can't make. You can't re establish a strong iron difference that's appropriate, so you're strong and difference gets smaller. Hence you become more acidotic. Hence renal tubular acidosis. Diuretics, as I said earlier, will remove more chloride than sodium, so the relative, um, difference will be increased. So you're strong. I difference will get bigger, more space in the attic, more space for a wage. And you'll therefore get an alkalosis. And CO2, as I said earlier, is the rapid adjuster. So if I suddenly get a lactic acidosis or a keto acidosis from my insulin dependent diabetes, I'll start breathing. Mike Metal start what they call co small breathing. And so I'll get I'll reduce my CO2 to try and adjust the amount of bicarbonate that's being taken up in that space by the strong I difference. And so I can therefore make at least try to improve on the oh eight. So I have. I don't overdo the acidosis, and I try and maintain, um, my acid base balance and chlorides for the longer term period. So that's the kid. The lungs are rapid and the kidney through chloride removal is longer term, so to recap, and we've said over the last two lectures there's a lot in this I know one we said right in the beginning. The reason acid base is important. The main reason is, is because Why is it disturbed? Not the disturbance itself within, you know, bounds of reason. That's why. So if you have a lactic acidosis due to sepsis, that will double your mortality, Uh, depending on the the quantity and hyperchloremia acidosis. Despite what a lot of people say, you look carefully at the literature. There's not a lot of influence on prognosis, so it's the cause that's important. We define what an acidosis was. Using simple terms like an acid is more H plus and O. H minus and bases more O H minus and h plus. We talked about a strong electrolyte, like the salt being thrown into water. When you're making spaghetti, there's no salt in salt and boiling water. It's also any plus C l minus and a weak electrolyte that only partially so you throw a B and there's some a plus. There's some B minus, and there's some. Maybe we talked about the traditional methods that I use all the time for the simple cases When I don't have, you know, I don't have to scratch my head to see what's going on here. And there's like, for example, the Davenport diagram that I use. I like this. If you use this. It's very simple. Uh, doesn't really explain a lot, but it's It's a simple way of doing things. It's a rule of thumb. You also have the other approach, which is the base excess or based deficit that's purely a metabolic approach to a metabolic acidosis or alkalosis. That's basically titrating the amount of acid or base you have to add to bring your solution to a normal pH of 7.4 in a CO2 normalized environment. So the respiratory component is removed. And, as I said, it's an average of several opposing influences, or it can be an average, so it doesn't explain the cause, but it gives you a sort of an overall idea what's going on. We talked about Stewart's now that was this. Lectures coming. Focus. And that's how it's considering the physical chemistry of pure water and the influence of strong ions, week ions and CO2. These are the independent variables that will determine the dissociation of water. We talked. We did. We built our gamble or our columns, and we saw how you have a space defined by the strong difference. So that's like the attic, and you're gonna fill it with various elements. And NATO is just another term for album. And and, uh, and how we use that, we again repeat that we talked about three independent variables. Strong indifference week ions, that's albumen, the century and CO2. And how the other variables, according to Stuart, are dependent. And lastly, I used several clinical examples and the simplified approach and the thing. I like the most of these sort of these columns or these, uh, these bars that give you a visual effect of what's going on in that person's, uh, acid based environment. And you can therefore possibly correct them like the diabetic ketoacidosis going from a keto acidosis to a strong iron difference acidosis, and therefore the treatment will be different. Okay, so to conclude, I would say in uncomplicated cases, go to the traditional methods. The Davenport diagram or just based success method in complex cases take the time to understand and use the stewards method that will really make it very useful, and it will help you in your therapy, and that's really all I have to say about that. Any questions? Mhm. Uh, no, thank you for that. I think that's really helpful. I think it's more of the application. I need to just kind of, like, fit in. So Yeah, and I think you summarized it. Really? Well, um, that the point that I was trying to think about earlier on, uh, obviously, by increasing the chloride, you're reducing that strong iron difference. So it's not necessarily the issue with saline, because obviously that's got normal similarity, right? But I suppose what you're doing is by reducing that strong iron difference at the, uh is it so the strong irons? Yes, there's less space for them. I the album in and the chloride, all these other ones bicarb and therefore that will kind of that Will that will, cause this equilibrium is such Is that correct? Is that it? Squeeze, Squeeze it, squeeze them out. Basically, the albumin may not change very quickly, but the CO2 and hence bicarbonate, which you know when they're they're the same. Some ways will rapidly change because you'll breathe it faster if you're more acidotic. Um I'd be careful. One thing. It's not the size of the chloride. It's the difference in the sodium and chloride. So if my chloride went up by 10 but my sodium went up by 10, there'll be no difference in a strong iron difference. Okay, um, so it's a difference between the two strong iron difference. And as I say, if you had lactate, there's no change in chloride. But it's a strong eye on. And so hence your attic. If I can keep using that stupid analogy, um, or simple analogy is smaller. Hence, you have less space for bicarbonate because you're gonna probably breathe faster and get rid of CO2. And also, um, you're gonna drive away into solution so you're going to reduce the amount of Oh, wait, you have. Which means your solution be less acid, more less alcoholic. Don't forget, if you're seven p to 7.5, you're still alcoholic relative to 7.4. But in absolute terms, you're still because you're quite alcoholic in biology. Okay, I think it's gonna you're gonna need to look at this. Uh, I mean, I know I some of these talks I think Once you get this down, you'll carry this through with your career, and it makes it. It's worth investing a little bit of time going through them because they're not easy topics. But then again, I'm not trying to give you a cookbook recipe that you can get in any book read once and forget about. I'm trying to give you something that you can actually try and understand. There's actually quite a bit of pleasure and finally understanding something, but then actually can apply it throughout your career. I know. Uh, I do so the example that you gave obviously with the asthmatic patient. Obviously, you know, you rec, I can see why the other physician considered giving you bicarb to basically just treat the numbers as opposed to treat the patient. And obviously, by doing that can cause an intracellular acidosis, which you can ultimately make things a lot worse. Um, but obviously you again. You said you gave furosemide because obviously you can diaries hydrogen, and that's your way of kind of dealing with numbers. Diaries chloride? Yes. Sorry. I think you You know, I'm not trying to say use frusemide for us, but I'm just trying to use that. As an illustration of, you know, in a panic, I believe you have to go. I think we have to go because I think there's another way. Okay, thanks. Okay. Thank you very much. Doctor, We do have the next lecture right now. Starting now. So thank you again. I will.