to move through and get started. I have no declarations or disclosures to declare. And if all of you would be so kind on your devices to get to this website www.menti.com and the poll number that we're going to be using is 661346. It'll be at the top of each of the slides that we're going to use as well. So if you don't quite get there in a moment there will be other opportunities to join. So what I want to say here is that acid-base interpretation is very challenging. I don't know if I speak for everyone in the room but I don't know how many times I've had to read through some of this material to feel like I actually had some sort of attachment to it or could access it in my head. I think that's compounded by a number of very sort of confusing and very long history of acid-base interpretation and some of the you know issues that have arisen over the years as technology has become more of our friend. These are complex chemical concepts that are again difficult to sort of intellectualize I guess. And so I this is my own top 10 list but I think it's probably on one of the top 10 lists of most difficult things to learn in vet school. And pretty much the only way that I've been able to get through it is to read and read and read again and read again and read again and keep practicing and practicing. So what I present to you is kind of born out of my own struggle to try to have a handle on some of these things and I would consider myself really only very much an amateur when it comes to mastery of these kinds of concepts. So if anything that we're talking about today is kind of don't panic come back to it and come back to it and come back to it and eventually it will be yours. I promise. So why is it then that acid-base is important? Why is it that the body is focused on regulating this aspect of what it does? And really it is an attempt probably to optimize the internal environment for cells. The blood flow that comes to all of the cells is essentially providing the raw materials and fuel and it's prepared to take away all of the waste products from these cells. And that optimization of the internal environment includes regulating the acidity of that environment and that allows for what we call optimal environment or optimal management functioning of the intracellular environment. This smart person named Davis in 1958 decided that it might be useful to have a theory about these things and so he postulated that nearly all of the known low molecular weight and water-soluble intermediates are ionized at this neutral pH. And when things are ionized it allows the cells to regulate them and manage their transport much more easily. And so phosphorus, ammonium, and carboxylic acid are probably the most common ones that we see being ionized and these are again really important in many many different metabolic pathways. The other thing that he identified was that proteins function optimally when their net charge is kept constant and this conveniently also happens at this ideal neutral pH. Okay so those are some of the reasons why acid-base balance is critical to understand and so we're going to start perhaps on a bit of a historical journey through the development of acid-base theory and how this found its way into the clinical arena and especially into the emergency and critical care realm. I think that helped me a lot to gain some perspective and to sort of see it from a bit of a historical or evolutionary perspective and allows us to put some of the different mechanisms and tools that we use into some perspective when it comes to these sorts of things. So over time there's been a great deal of people who've talked or put out a theory as to what actually is an acid when it comes to chemical activity and behavior. And so that stretches back far back into history where the early chemists in antiquity determined that acids would share the following properties that they had a sour taste, they turned litmus red, and they reacted with some metals to produce flammable gases. Rather exciting probably in the early days but that was how they defined what an acid is. And then hard really even to believe then in 1887 people were talking about these things but they absolutely were and a man named Arrhenius was really among the first of the modern chemists that we think about sort of stretching back to our current thinking. He was able to define acids as substances that were capable of dissociating in water to produce hydrogen ions, which really is a lot of the concept of an acid I think that we many of us still think about today. Bronsted and Lowry contributed in again a few decades later in 1923 to sort of polish this up a little bit. This theory was also quite popular among biological and medical disciples because it was simple and encompassed again many of the exceptions that had been found to Arrhenius's definition. And so these two gentlemen came up independently and so they again decided to collaborate. I imagine that in today's world where scientists in two different countries decided to just name a theory after each other instead of having to name it after themselves. So Bronsted and Lowry talked about this theory where acids were substances capable of donating a hydrogen ion to another substance. And finally as inorganic chemistry sort of took on a life of its own we had Lewis who also postulated a theory around the same time interestingly enough, but his theory became more popular within the chemistry world itself. And his postulation was that acids were substances that can accept a pair of electrons to form a covalent bond. And so it's interesting to see how these definitions kind of are similar and some that we don't really think about very often until we're through our organic chemistry and pre-vap. So the other thing to understand about acidity is that it's really difficult to actually measure. Bare protons, even though we tend to think of them as having a life of their own, don't really actually exist in the chemical world. So this reality is a bit tough for us to take into consideration because when we learn about it and think about it that's how we think about them. And so we often use hydrogen ion concentration out of convenience or convention. Stewart, as you'll hear Dr. Hopper talk about later today, he said that hydrogen ion concentration is a symbol of a metaphor, a very mysterious concept. But it's important I think to understand that hydrogen ion activity is something that is much easier to measure. And this concept of chemical activity is really formulated in this fun little formula where the activity of a substance is equal to the coefficient, activity coefficient, times the concentration. In most biological solutions the activity coefficient for most chemical species is one. So for most things their activity is equal to their concentration, but that isn't necessarily always true. But for the purposes of what we think of it is fairly commonly applicable. Okay, so out of this mess comes the concept of pH. This concept was first introduced by Dr. Clark in 1920, but it had actually been invented by a Scandinavian chemist in Sorensen in 1909. He had labeled it or named it something slightly different, but the concept he had was there. It was popularized really by Clark. And that was that the pH is equal to the negative log base 10 of the hydrogen activity. It really is what we think of as a dimensionless representation of hydrogen ion concentration. So it's a formulated concept in order to try to have some ability to measure something that's hard to measure. So some people still like to talk about hydrogen ion concentration. pH is a related concept and something that is probably much more popular to talk about than hydrogen ion concentration. And in fact, the international body of clinical chemistry recommends the use of pH as opposed to hydrogen ion concentration. Because in their view, it's traditional, it's in widespread use. It's related to the activity of the hydrogen ions, not necessarily their concentration, and therefore it's a more physiological concept. It's actually what pH electrodes measure is the activity of hydrogen ions and not their concentration. Hydrogen ion, again, concentration is thought to be incorrect because the activity coefficient is not included as part of that concept. And again, we come back to this idea that free hydrogen ions actually can't exist in by themselves for us to actually measure. So pH is a fun little concept. And I found this little chart to be quite helpful in understanding, you know, because we don't think in logs and base tens typically very easily unless you have a really strong mathematical mind. So this helps me, I think, in understanding how to relate these two concepts together. So on your right hand side is the concentration of hydrogen ions in theory that the pH, which is on the left hand side, would actually measure. So you can see, for example, at a pH 7.4 that the hydrogen ion concentration is around 40. If we were to double the hydrogen ion concentration to about 80, we now are at a pH of around 7.1. Okay? So for every doubling of hydrogen ion concentration, we move the pH by about 0.3 units. Okay? Also convenient to remember is that a pH of 7.4 is 40 nanomoles per liter of hydrogen, and a pH of 7 is 100 nanomoles. And also a very fun little trick is that this normal pH range of 7.36 to 7.44 is actually a range of hydrogen ion concentrations from 44 to 36 in reverse order. So just some useful reference points to have when you're talking about pH. There really is a constant turnover of acid in the body. On a daily basis, if you are a carnivore or an omnivore, you're typically having a net daily production of acid, and you will need to have a net acid secretion in order to maintain this neutrality that is important for all of our cells to function optimally. This acid production is comprised of really two different species of volatile acids, which largely are carbonic acid, which turns into carbon dioxide, and we breathe off, so it's volatile. We can get rid of it from the system quite easily. And that largely comes from carbohydrate metabolism and amounts in humans at least to around 200 millimoles per kilo per day. So a fairly substantive amount of acid. When we look then at fixed acids, which again we would probably tend to think of more as our metabolic acids, our non-respiratory acids, these are things like lactate, the keto acids, phosphate, sulfate, those kinds of things. Originally, these were thought to be resulting from incomplete metabolism of carbohydrates, fats, and proteins, which they can be, but they can come from other places as well. And on an equimolar basis, we only really have about 1.5 millimoles per kilo per day production of these fixed acids. So they're much less challenging perhaps to try to deal with from the body's perspective. Now, again, in this theory, and for those of you who are more advanced in your thinking, you'll recognize that strong acids like sodium, sorry, strong ions like sodium and chloride can also have a role to play in acid-base balance, and we haven't really considered those in here at this point in time. Again, mostly because they are fairly highly regulated, and we don't tend to try to get rid of those on a daily basis. So now we hit the backbone of our fundamental understanding of acid-base balance, and that's the Henderson-Hasselbalch equation, which again comes along in this early part of the 20th century. And it's important to recognize that the theory, the chemical concepts, and the formula itself was originally designed to look at all kinds of different acids in solution, and it applies to those acids, not just to carbon dioxide or bicarbonate and carbonic acid. So you'll see the top formula on the screen there has this A minus over H A minus concentration, which is important to remember that you can actually apply it to systems other than, or acid and base pairs, other than bicarbonate and carbonic acid. Because carbon dioxide, bicarbonate, and carbonic acid are really the main species that we're interested in talking about, because it is the biggest volatile acid in the system, and because it's such an important buffer, we often have replaced those original designations in the formula with bicarb and carbonic acid. Okay. It was a largely theoretical consideration. Remember that blood gas machines didn't exist in 1917. There was no real way to measure any of these things, and so it was basically a theory that had been postulated by these two scientists, and kind of existed that way for a number of decades. It turned out to be quite prescient as we got more into this and developed additional things, and so became very, very important later on, because it did represent a lot of what we wanted to understand about this. So pretty cool that these two gentlemen had the foresight to see all of this in the future. Let's move now on to the early 1950s. Things stayed pretty much the same. There had been this big flurry of intellectual activity in the early 20th century, and a lot of people got very involved. It was a very busy and very productive time for thinking when it came to these kinds of concepts, and ultimately there was a gentleman, I believe of Dutch origin, van Slyke, who created this apparatus, which was starting to become in use in some of the most advanced human hospitals and labs around the world. It was able to measure a couple of things, including carbon dioxide and pH, and so using the Henderson-Hasselbalch equation, they then back-calculated through that whole process to try to calculate what bicarbonate concentrations were. It also measured oxygen concentration, which was of interest, and so really you can kind of think of this as a very early and very crude blood gas machine, and was about to play a really, really important role in the development of modern medicine and emergency and critical care medicine, for sure. And that's because in the early 1950s in Europe and around the world, and we're going to sort of visit this in Copenhagen, which was one of the first cities to have a polio epidemic develop, and in the 1950s when this happened, and again Copenhagen being one of the epicenters of this outbreak, they had the main hospital in Copenhagen had over 3,000 patients present to it during the epidemic, and many of them developed respiratory paralysis as part of the illness. And so many of our modern tracheostomy tubes were developed during this period of time, using trial and error. The ambu bag that we're all so familiar with in resuscitation was developed during this period of time, and you can be glad you weren't a medical student during this period of time, because classes were canceled and all of the medical students were in the hospital handbagging all of these patients who couldn't breathe with their tracheostomy tubes. And of course medical students aren't probably as accurate as some of our modern critical care ventilators, and so there needed to be some mechanism that the attending clinicians had to assess whether the ventilatory rate and the minute volume was adequate for these patients, or were we allowing them to, you know, have respiratory alkalosis or acidosis depending on how overzealous the medical student attending you was that day. So the Van Slyke apparatus got a big workout, and there was a really interesting guy who, in that hospital, really saw the need now for this to develop. And so he started working with his brother-in-law, who was kind of like a tinkerer inventor guy, and they formed a company called a Radiometer, which many of us will be familiar with. And that was the company that first manufactured, in the late 1950s, a blood gas machine as we would tend to see or imagine it looking like today, and it's basically just evolved in that way since then. So from the late 1950s, early 1960s, blood gas analysis has been part of our sort of clinical lexicon, but because of its historical origins and very much focus on respiratory distress and respiratory acidosis as part of the polio epidemic, it has, and again because of its historical roots and what we could measure and couldn't measure, it is essentially a very bicarbonate CO2 focused assessment of overall acid-base balance. It's important to recognize that it gives us a piece of the puzzle, but there isn't a machine that actually helps us to sort of do an overall assessment of acid-base balance and buffering capacity in our patients. These approaches were simple. They allowed us to categorize and explain most of the common simple acid-base disturbances that we were starting to identify, but this approach was not very helpful in understanding complex patients who maybe had more than one thing going on at the same time or who had multiple disease processes that were starting to affect us. So think back again to the slide we had a couple of seconds ago where we were, you know, talking about some of these other sorts of fixed acids like lactate, phosphorus, sulfate, obviously our strong ions. None of these kinds of players were really being measured or understood as part of our routine blood gas analysis, and so people started to think of ways and investigate ways that we could explore some of these things, have a handle on them in order to improve our accuracy and understanding of how to categorize some of these issues. And so, for example, the use of anion gap was born in this time period as a way for us to try to understand more about how these kinds of strong ions and other players were interacting in our patients. Before we move on to talk a little bit more about that, I think it's important fundamentally to understand buffering and the concept. There was a really interesting experiment as well in the 1950s, Swan and Pitts, where they added 14 million nanomoles per liter, so a very concentrated hydrochloric acid solution. They dripped it intravenously into some research dogs, and they measured the pH change over time as this pure acid infusion took place. And the only pH change they documented was from 7.44, normal, down to 7.14, okay? So if you go back to the chart that we showed you earlier, the hydrogen ion concentration in those patients went from 36 to 72 nanomoles per liter of hydrogen ion's concentration. So people, you know, it's a difficult concept to understand. This is a concept hopefully that most people can understand. And this essentially equivalents to putting 14 million dollars in your bank account and having your bank balance only go up by 36 dollars, right? That's how much buffering capacity these dogs had to take this enormous amount of acid and buffer it, take it out of activity, so to speak, and allow us or allow the patient to, again, optimize the pH balance of inside and outside these cells. So the major, as Henderson and Hasselblock predicted and envisioned, the major buffer here that we want to think about using their equation is the CO2 bicarbonate carbonic acid system. And it is a remarkably effective system, again, because it's an open system. It's volatile. What we can create from there is a volatile acid, carbon dioxide, which can leave the system and we can get rid of this acid very easily on a continuous basis. It's effective as well, again, even at this low pKa value, because it is an open system and there's an escape for it. So bicarbonate is by far the predominant buffer that we need to be thinking about, but it's important to recognize that there are a number of other buffering systems in various systems within the body or locations within the body. And so in the interstitial fluid, bicarbonate and phosphorus and proteins are predominating. Sorry, the bicarbonate is predominating. In blood, we have the addition of hemoglobin, which is a really important carrier for carbon dioxide, and therefore acts as an important buffering system or contribution to the buffering system there. We have a lot of plasma proteins, which can, again, also hang on to some of these acids and hide them in the forest of negative charges that typically surround them. And again, phosphorus, not really that important in the bloodstream because its concentration there is really too low. When we look inside the cells, you won't see bicarbonate there, right? Bicarbonate is really this major transport buffer that happens in the bloodstream and in the interstitial space. Inside the cells, we have proteins and phosphorus, where phosphorus is, again, in a much higher concentration inside the cell. And we have this large concentration of proteins, which, again, largely negatively charged and can buffer these hydrogen ions or protons quite easily. In the urine, again, we have phosphate and ammonia, which are, again, complex concepts. See, that's a hard word even to say. And we're not going to touch much on that because that's a whole other renal physiology talk. And not to forget bone, where calcium carbonate is really quite an important player, especially in chronic non-respiratory acidosis, where it can really store a lot of acid as a major buffer there. Okay, so important to have these kinds of ideas about acid base balance that if you focus too much on carbon dioxide bicarbonate, you are going to sort of lose some of these bigger concepts and miss the forest because you're too focused on one of the trees. So stepping back into our little jaunt down history's lane here. Again, it's very interesting to see how this historical controversy plays itself out still today, in that from the late 1950s, there was a very, like, this is like the Iraq War of acid base balance, where Europe and the Americans were at each other's throats over how we were to understand and whose theory was going to take focus on this debate and move the needle on how we understand these things. And so in Copenhagen, again, which, as you can see from my little talk, I'm kind of impressed by what came out of that town in the 1950s. Here's yet another important consideration. And that Sigurd Anderson, again, two physicians developed this concept of our base access approach, right? So if you're familiar with acid, or sorry, familiar with acid, familiar with blood gas printouts, you'll see on that printout a number of iterations, probably on most modern blood gas machines, a base access, a BE. In North America, we don't pay very much attention to that, because, of course, the American centric theory, which we're going to talk about in a second, has really been part of our understanding, our fundamental understanding and how we learned about acid base in school. In Europe, and other places in the world, the base access approach is the predominant approach. We largely ignore it. It started to sort of creep into a lot of our literature here in the last couple of years, 10 years or so, in looking at base access, tying it to mortality and outcome and those kinds of things. So it's actually a pretty simple concept to understand, and can be a really, at least how I think about it now how I've evolved to think about it is it's a really useful way for me to sort of check myself. As I've done my interpretation using the more traditional rules and compensatory responses, understanding, which we'll talk about in a second, I'll often go back to the base access and go, hey, does this check out with what I just discovered or calculated? And if so, then I feel like I'm on the right track. If they're differing, then I obviously need to try to explain that a little bit in some way. So this concept of base access essentially tries to take a patient's sample and normalize that sample, take away any respiratory contribution to the acidosis or alkalosis that's present in that sample. So we take that sample and we would equilibrate it to a PCO2 concentration of 40 millimeters of mercury, which is pretty close to normal for most species. And we hold it at 37 degrees C. And then if we have to add acid or alkali to that sample, we measure how much acid or alkali we would need to add in order to bring the pH of that sample back to 7.4. So as I think about this, this concept essentially is the magnitude of your base access really tells you a lot about the magnitude of the non-respiratory component of whatever is going on in your patient. It takes away whatever the respiratory system is doing and gives you kind of a nice, easy number to look at to understand the magnitude of your non-respiratory disturbance. Okay. So moving on from there, there were a couple of gentlemen, Schwartz and Relman from Tufts, who didn't like this approach. They felt that it was not fair to take a sample out of the patient, put it in a machine, because there's so much other buffering capacity available in the interstitial space that we're not really considering when we take a blood sample out and put it in a machine, that it was an artificial environment. And this base access approach really doesn't work very well when we're dealing with chronic respiratory conditions, because there's, again, going to be so much bicarbonate retention in those situations that it sort of masked our ability to use base access in those particular circumstances. So they argued that this is too simple, it's not helpful, and we need to have a more evolved concept to base this on. And so they essentially developed the original compensatory rules of thumb for the six primary acid-base disturbances from which the research in veterinary medicine has evolved, and we've developed our own mathematical calculations to check for compensatory response in these systems. So again, two concepts, probably most of you didn't learn much about the base access approach or don't use it routinely, and focus more on this compensatory formulas that we use to calculate whether or not patients have adequately compensated for their primary acid-base disturbance. And then along comes Stuart in the late 1970s, and I'm proud to say that Stuart was from Canada. And finally, some people outside of North America or outside of America and Scandinavia were contributing to this concept. So Stuart's concept could not have happened before 1970, simply because computers were not smart enough to solve the mathematical quadratic equations that he had developed to try to actually measure some of the concepts that he was thinking about. So he based his thinking on the concept a little bit more like Arrhenius' concept of an acid, and again, brought these strong ions back into the fold, knowing that they played a role, and we were sort of trying to get a handle on them using our approach of the anion gap. He brought them back in to this whole concept and said, like, let's actually try to put a handle on everything here that's playing a role in acid-base balance and see if we can have a better understanding of things. His approach allowed us to explain a lot of the exceptions that weren't really covered by previous theories. And again, Dr. Hopper will be focused much more extensively on how his concept has evolved and how we would tend to utilize it in clinical medicine today. But these are really the major theories, trying to give you a bit of a historical context and timeline for how some of these things developed and why they developed, and why we have some of these idiosyncrasies of how we interpret acid-base today. So with that, I'm going to invite you to try out our audience polling system. And I'm really very much more interested in you being honest with me. You're not going to hurt my feelings whatsoever. Tell me what you thought of this historical information that I just presented. The code is at the top there, 661346. It's working. This is good. I have five responses. Good. It looks like most of you found it helpful, interesting, informative, so it's good to know. It's one of the first times I've sort of presented it in that way, so I'm glad to know that it was helpful for you. So we will move on to our next question, which is... We could play this a couple of ways today. I can sort of do a bit of a background on sort of a step-by-step approach, how to interpret a blood gas using these sort of traditional concepts that we've been talking about, or we can go straight to cases, or your other option is we can all just pack it up and go to Disney for the day. Great. Looks like most people would be happy to have a bit of a backgrounder, so we will go there. So what's a blood gas? Let's start there. Recall that the Van Slyke apparatus was able to measure carbon dioxide, pH, and PO2. That's what our modern blood gas machine measures, too. We haven't actually evolved a whole lot from the Van Slyke, other than we now add some electrolytes and lactate and a few other things along the way, and we have a lot of fancy calculated values that actually come out onto the blood gas machine as well. So as we've talked about, again, remember that this piece of paper really offers us only a limited view of acid-base balance and the oxygenation of our patient. It can be useful for a number of situations, especially when it relates to acid-base balance, to help us sort of maximize our fluid therapy approach. But it can also be really helpful in managing respiratory disease, as it was in the 1950s during the polio epidemic. So here's what a typical radiometer printout looks like. And again, you can see that there is a large number of values there, remembering, of course, that only PCO2, PO2, and pH are actually measured values. The rest are calculated using normograms that are typically derived for humans, and most of us or most manufacturers of these machines don't necessarily have the research or background to make adjustments for the various animal species. So we've evolved using a lot of human mathematical activity in these machines, and we've just learned to become reliant on what those results look like using those kinds of mathematical approaches for our patients. So from this, and this is very simple because I use this approach to try to help vet students understand this. So forgive me if this is too simple for you, but step one here is to decide in these patients whether the pH is greater or less than 7.4. Is this an acidemia or an alkalemia that I'm dealing with? And have to try to understand and explain. I should back up for a second and let you know that I did provide you with a copy of the next series of slides. These are the steps that I go through and the sort of different tables and formulas that we typically use to try to do our assessments. So you might find it helpful to follow along there. I've provided these because as we're finished this, the rest of the time that we're going to spend together is going to focus on cases, and you'll probably want to have some of these references and some familiarity with this approach to be able to play along with the quiz that we're going to have next. Okay, so once we get to that, we move on to step two. And in step two, we're going to examine both the PCO2 and the bicarbonate values that are on the printout and decide using what species and what the source of the blood sample is, whether it's venous arterial, and decide whether those values are above or below the midpoint of the reference interval that's been calculated. So these reference intervals are sort of generic. They might not match what you're currently using in your practice depending on what machine you're using and what reference interval you've got programmed into your machine. So if you have your own values, you can plug those in to this table when you get home, right? But what we want to really emphasize here that the, say, the venous dog PCO2 concentration, if I were to take the reference interval and divide it in half, that 37.4 is the value that I'm going to compare my patient to and decide is my patient above or below that number. And then if it's not intuitive to you what's going on, this table kind of points you in the right direction as to what the primary underlying acid base disturbance is and what the compensatory response, if any, is occurring is taking place, okay? So the way this works is that on the top line here, if you have an acid or an acidemia that you're trying to explain, you'll use the top line. And if you're trying to explain an alkalemia, you'll use the bottom line. And then after you've determined whether the PCO2 and the bicarbonate are up or down, you find the column that matches the directions of those two arrows to find what the acidemia explanation would be or the alkalemia explanation would be, okay? So this will hopefully become easier when we move into a case here in a second. Then we're going to, again, because we're North American and we like the Tufts approach, the Boston approach to determining acid base, we're going to calculate what a compensatory response should be taking place to determine whether the magnitude of the patient's response is matching the expected response in order to determine whether there is more to this story than a straightforward, simple acid base disturbance, okay? And so most of the time, if you play the odds, the vast majority of acid base disturbances that we see in our patients are non-respiratory or metabolic in origin. And so this magic number right here is one that I've committed to memory. I don't necessarily remember all of these for the respiratory acid base disturbances because we don't see them as commonly. But for sure, the 0.7 millimeters of mercury conversion is an important one to think about, okay? So if you have a non-respiratory disturbance, you want to be able to determine how much change in CO2 should be taking place for every one milliequivalent change of bicarbonate that has occurred in your primary acid base disturbance, okay? And so as the patient moves as part of that, again, we get a little touch and go with some of the nomenclature here. So if this is pH 7.4, we have a primary non-respiratory acidemia on our hands. And so the patient's had a non or volatile, sorry, fixed acid accumulation and their bicarb has decreased by a substantive amount. What we want to use these for is what's happened to the CO2 concentration. So normally the CO2 concentration in when it's compensating for a non-respiratory acidemia is that the CO2 concentration will also go down in order to try to neutralize the pH again. So as it goes from normal down, down, down, down, down, we now get into this compensatory range here where the actual is within two millimeters of mercury of our expected magnitude of compensation. And so if it reaches that point, we're going to call it compensated. If it started here, but it didn't make it to that expected compensatory range, we call it uncompensated. Some people would confusingly call this a mixed acid base disturbance. I don't like that term because it doesn't really give me a good sense of that. So I prefer to use uncompensated in this range. And if the CO2 concentration actually went lower than what we would expect the compensatory range to be, then we now term that a mixed acid base disorder because there actually is a significant acid base disturbance in the respiratory system as well. If we are concerned about respiratory function and gas exchange, we can also calculate the PF ratio where we simply divide the PaO2 by the FiO2 if it's being measured or gas if it's not. And this is a really simple, easy method that is applicable across all FiO2s, whereas the AA gradient calculation technically should only be performed on room air, breathing room air, which is kind of hard to do if your patient is really oxygen dependent. It's not really fair to them to take away the oxygen to measure proper AA gradient. So we prefer the PF ratio. It's a lot easier to calculate. And the reference interval, again, anything over 400 is normal. Anything under 200 would indicate very severe pulmonary disease. It helps us to understand how many functional alveoli are participating in gas exchange in these patients to have a sense of how severe the lung injury actually is. When we look at clinical guidelines for, you know, when do we panic, what's important from these numbers, again, I think we probably, if you ask 10 people, they would quibble a little bit about where some of these numbers are at. But generally, these are the magnitude of changes that would tend to cause me to sit up and take notice and perhaps intervene in the patient. So if the acidemia is bad enough that my pH is sort of under 7.2, 7.0, and especially if the bicarb is less than 10 concurrently, then I'm going to want to try to be a bit more aggressive in managing that. Likewise, if the pH is over 7.6, we're going to probably be more concerned about that. So you can see, again, this discrepancy between how well patients tolerate acidemia versus how well they tolerate alkalemia. The system is far better designed to tolerate an acidemia. And we can, you know, go down to a pH of 7.0 without there being any major clinical consequences. But a pH above 7.6, which is not really that far, can actually cause seizure activity to occur in these patients. So it's not built as well to tolerate an alkalemia. When we're looking at respiratory failure, again, PO2 less than 60, oxygen saturation less than 90%. These are numbers that are going to potentially cause us to think about using high flow nasal cannula oxygen support or consider mechanical ventilation, if appropriate. And likewise, if the PCO2 is over 55 on either a venous or arterial sample, then we're going to be a little bit worried about respiratory failure, inadequate minute ventilation, and potentially need to intervene with mechanical ventilation in those patients. So again, you've heard me say in this historical approach, we're very focused on the bicarbonate CO2 buffering system. But, and most of our blood gas results are focused on that system and focused on that buffering system. And we're very focused on volatile acid production in these patients. But there's all of this non-volatile, non-respiratory acid system that is a bit more difficult to kind of get a handle on. And so as we've talked about, there are many approaches that can be taken to try to understand and categorize this aspect of what happens in acid-base disturbance. And so these kinds of approaches are using the anion gap, which was sort of the original approach to things. People added a little wrinkle on that to try to have a better assessment of when there might be strong ion differences involved in that. And so added on this sodium chloride difference to that. There's also the Gamble-Graham approach, which kind of is a hodgepodge mixture of sort of these two approaches. And then finally, we also have the Stewart or the non-traditional approach, where Stewart, Fensel, and others have put forward all of these mathematical calculations to try to allocate and apportion various components of acid-base disturbance and understand the magnitude that each of these things may be contributing to the overall acid-base situation. Oh, look at me. I'm way behind here. Sorry. So as we're looking at the anion gap and the sodium chloride difference, we can utilize, again, these are generic reference intervals. These are the mid-range of those values, something to compare against. Again, if you'd like to replace these values with the things or the reference intervals that you use in your practice, that would be amazing. And so finally, as we move into these final steps, these are ways that we're trying to dig into or dig at what's happening to some of these other non-respiratory components of the acid-base disturbance in order to try to explain and understand them a little bit more carefully. Here's the sodium chloride difference. It's pretty simple. And again, those are the normal values. Hopefully, you'll see that in action here in just a second. And so using these tools, and again, in a lot of textbooks that use this approach, you'll see categories then of common acid-base disturbances that fit into this approach. And again, we're going to talk a little bit more acid-base disturbances that fit into this increased anion gap category. So our ethylene glycol intoxication, DKA patients, renal failure, lactic acidosis patients. And then for patients who have normal anion gap are renal tubular acidosis, patients who are on carbonic anhydrase inhibition, and patients who have a lot of bicarbonate loss in their diarrhea as fitting into these different categories. Likewise, for the alkalosis, these chloride responsive versus chloride resistant categories. And then finally, if we add the anion gap and sodium chloride difference together, we can sort of use this chart to direct us right into the specific categories that we're going to need to be focused on. How many people know the Gamble-Gram, love the Gamble-Gram, use the Gamble-Gram? Anyone? A couple of people? I love it. It's my favorite thing. So this concept is built in this way. Essentially, again, Stuart's approach says that law of conservation of mass, we have to have an equal number of anions and cations in circulation in order to be balanced. That's just the way the world works. So what we do on the Gamble-Gram is put onto this chart all of the clinically relevant anions and cations that play a role in acid-base balance and disturbance. So on the cation side of things, essentially, it largely boils down to sodium in veterinary medicine. In human medicine, we include this unmeasured cation category because some of the weird things that people eat can result in unmeasured cations. In veterinary medicine, our patients, thankfully, are smart enough to do those things not very often. And so it's really, really rare to see an unmeasured cation contribute to an acid-base disturbance. So essentially, on one side, we have sodium. And on the other side, we have the clinically relevant anions that contribute to acid-base disturbance. So largely, that's going to be chloride, our proteins, phosphorus. And because most of us measure lactate now, you could actually break the lactate out of the unmeasured anion box and put it in as its own category here. And therefore, we are left with the oxalate, sulfate, and keto acids as part of the unmeasured anions that might fit into this box. The other key thing to understand here, again, is based on Stewart's concept that there are independent variables and one dependent variable. So the independent variables are everything on here except for bicarbonate. Bicarbonate is the only dependent variable that occurs. And it's probably a bastardization of his concepts. But how I think about it is that everything gets to choose its own concentration and value here. There's not interactions between any of these things. And the kidney, who is largely responsible for regulating bicarbonate retention, is the dependent variable here, that the bicarbonate concentration is adjusted when all of these other ingredients get mixed into the stew. And we're adjusting bicarbonate to make the flavor taste great. Bicarbonate is adjusted, again, in order to account for all of these other strong independent things that aren't going to be responsive to changes in any of the other variables. So the way this works is, for example, if my sodium concentration has increased and none of the other independent variables have done anything, bicarbonate being the dependent variable has to adjust in order for anions to meet cations. And so if sodium increases, bicarbonate also has to increase, and that is therefore an alkalinizing process. Okay, so a hypernatremia will create an alkalemia if none of these other things change. Now, we recognize that sodium and chloride typically are going to be adjusted together, so they often sort of neutralize their effects on each other. But on occasion, you will see a patient where they are differently controlled, and that results in some changes that we can assess and quantify using this kind of a system. Okay. So the Gamble-Gram is fun from my perspective in that it helps me to sort of apportion and test the waters a little bit and trying to sort of improve or allow me to pick up on some of these other kinds of contributing factors to acid-base disturbance that I wouldn't normally be able to consider as part of my traditional approach, which is where I measure bicarbonate and CO2, and I think about it from a very simplistic perspective, and I look at compensation, et cetera. I'm missing a lot of these kinds of bits of information that might help me to understand this. I find the Gamble-Gram, once you've understood it, to be a really good way of kind of being able to use the Stewart approach to things without necessarily having to do all of the math that Stewart requires of you, right? So I find it to be very elegant, and if you can get onto it, I would encourage you to think about it. So that's how I think about acid-base assessment and how I would go about teaching and or doing acid-base assessment. And so we're going to move on to a couple of cases now, okay? First, no quiz. Everybody's on an equal footing. We'll do one case together, and then the rest of the cases we're going to have a bit of a quiz competition to see who can get the most right answers. So here you have a two-year-old Rockweiler. Anyone have one of those presented to them ever? The Rockweiler? No, okay. He's quite sick, vomiting, diarrhea all night, now bloody. It turns out he has parvo. Shocker. And so here are his numbers that come out from the blood gas machine, all right? So you see his pH, PCO2, bicarbonate, PO2, and base excess. So if I was going to follow my rules, my step one is to look at pH. It is less than 7.4, so this patient has an acidemia that I need to try to explain and understand. So I then go to step two, and I look at my PCO2 concentration and my bicarbonate concentration. The PO2 or PCO2 is less than 37.4, and the bicarbonate is less than 22.5. So I have two down arrows, and it's a pH less than 7.4, so I'm on the top row, and that tells me in that column that I'm needing to explain a compensating metabolic acidosis or non-respiratory acidosis. So the next step is to try to look at compensation that this patient is experiencing. So if you look back at his numbers, his bicarbonate was 11.1, and normal for this patient is 22.5. So the difference between those two numbers is an 11.4 bicarbonate, and from our compensatory rules for every one milliequivalent of bicarbonate that has changed, we should see an equivalent 0.7 millimeters of mercury of CO2. So that magnitude of CO2 change should be 8 millimeters of mercury. His PCO2, therefore, if we calculate what his expected range should be, if he is doing what he's supposed to, he's going to start at 37.4 and drop his PCO2 by 8 millimeters of mercury, which should be somewhere around 29 and change. His is 32.3, and so it is 2.9 more than expected. So it's higher than we expect it to be. It should be a bit lower than that. So he started at 37.4, and he's pushed his way down towards getting sub-30, which is where we want him to be, but he's not quite there yet. And so we're going to term this an uncompensated metabolic acidosis. And given what else I know about him, we look at his lactate, what his history is. He's probably lost a bunch of bicarbonate in his diarrhea. He's in shock. He's going to have a significant amount of lactic acid or lactate. And it's possible that he is now so sick, so cold, potentially, that his respiratory system is no longer functioning optimally. And he's starting to backslide a little bit here on us with this decreased respiratory function. So it's close enough that we have to start kind of trying to wonder why his metabolic acidosis is not compensated, because he really should have had time to compensate properly for it. So it gives me a sense now of how sick this patient is and the fact that I really need to probably intervene fairly quickly to prevent things from kind of going down south a lot worse. So here's our next patient. Here's the numbers. Oh, I want to go back to this as well. So take a look at the base excess here. Minus 16. Very simple. That tells me that there is a large magnitude non-respiratory acidosis in this patient. It's significant. A base excess of minus 16 is not something to take lightly. And pretty much when we do our calculations, we get to that same kind of concept. So that's how I would use the base excess as just kind of a double check against what my normal process would be to look at compensation. Okay. Great. So next patient is an immune-mediated hemolytic anemia patient who's been four or five days with this disease. Pretty severe hemolysis. You can see the numbers there. Again, look at the base excess. Minus 3. Very small amount of non-respiratory acid-base disturbance here. Kind of what we'd expect in an IMHA. And so as you see, there are some other significant changes up above. So that probably leads me in the direction that I'm more likely dealing with a respiratory acid-base disturbance. That was a hint. And then a non-respiratory acid-base disturbance. So if you go to your poll again. We have people coming here. So if you answer quickly, you get more points. 30 seconds to weigh in with your response. Nearly closing, perfect. So we had five correct answers, which is great. And metal is at the top of the leaderboard at the moment, followed by Katrina. So let's see how this plays out here. Let's go through this one together then. So the pH is greater than 7.4. We're dealing with some sort of an alkalosis. If we look at the numbers, the PCO2 is less than 37.4, bicarb is less than 22.5. And therefore, we're using the chart into some sort of compensating respiratory alkalosis. So that's what we're trying to determine and explain. So we now will look at the change in PCO2 concentration and determine the equivalent bicarbonate compensatory response. Given that this patient has been struggling for more than a day, more than 24 hours, this is more likely to be a chronic process. And therefore, we use the chronic respiratory alkalosis correction formula. And so if we say patient's 28.8 should have been 37.4, it's a change of 8.6. If we multiply that by the compensatory factor of 0.55, we say that the bicarbonate should have changed by 4.7. So the bicarbonate should be somewhere around 17.8, which is, again, normal, 22.5 minus this 4.73. So 17.8 plus or minus 2 if it's compensated. And he is 18.9, which is 1.1 different. So within that plus or minus 2, so this is a compensated respiratory alkalosis that's probably driven by this dog's anemia and poor oxygen delivery to the tissues. So moving on, here's a Sharpe who got operated on today for having a severe hiatal hernia and has been in hospital for a couple of days with severe vomiting regurgitation. This is an arterial sample. And the patient is on oxygen, likely just at the end of anesthesia for a surgical repair. So some impressive numbers here. Again, take a look at that base excess. And we'll, again, give you a second to start doing your calculations. So, for everyone who answered a mixed acid-base disturbance, you are correct. And it looks like, no, sorry, still calculating. Metal is still at the top of the leaderboard here. Okay, so for this dog, pH 7.4 is greater than 7.4, so it's an alkalosis. And again, when we look at PCO2 and bicarbonate, they're going in opposite directions. PCO2 is less than 7.4, and bicarbonate was greater than 22.2. And so any time that happens, we automatically put ourselves into a mixed acid-base disturbance because they really should be moving in the same direction if the process is compensating properly. And therefore, again, we can assume that this patient probably had significant upper GI vomiting and regurgitation to create predominantly a lot of this issue, pain, stress, anxiety. We're probably creating a lot of the excess respiratory drive and increased minute ventilation to drive the CO2 down. Either that or the patient was on mechanical ventilation inappropriately at too high of a rate and had blown off excessive amounts of CO2, creating a respiratory alkalosis. And because of this likely upper GI vomiting, we're probably losing a lot more acid from pure stomach contents vomiting, creating or leading to some of this metabolic alkalosis as well. So double whammy, which means that his pH was quite high at 7.66, putting him into the range of kind of a danger zone. So important to take that into consideration. Again, his lungs look great. His PF ratio is 487, which is quite normal. So the next day after surgery, after he had some pain control and some other things going on, we get this result. So again, take a look at those numbers and begin your calculations. I may have messed up this poll, gone too far. Are people able to weigh in? No. Sorry, technology got the better of me. So we'll go through him quickly again. He now has an acidemia. And when we look at the values here, both of which are higher than the midpoint range of normal, that puts us into a compensating respiratory acidosis situation. And when we do the calculations again, his CO2-56 minus 37.4 is a change of 18.6. We assume that this is an acute change, since this is within 24 hours of the day before. That would put him again into this 2.79 change in bicarbonate. If we assumed potentially that maybe surgery and anesthesia ventilation was inappropriate, and in fact he does have more of a chronic issue, then we can do our chronic calculation here, which would be 6.51 change in bicarbonate. So if this patient is in acute respiratory acidosis and it's compensated, then his bicarbonate should be 25.3. If it's chronic and compensated, his bicarbonate should be somewhere around 29. His bicarb of 30.5 is 1 and 1 half more than what we would expect for his chronic compensation. So chances are good that this is likely the case for him. So there's potentially some different ways of explaining this particular case. But given how those numbers fall out, that would probably be my guess. And that because he's a Shar-Pei and potentially on a lot of pain meds, maybe too much, maybe he's still quite painful from his surgery and he's not breathing with an appropriate amount of minute ventilation, he now has some significant CO2 retention or has had a lot of CO2 retention for some time, and his kidney is pretty upregulated with respect to that and able to retain bicarbonate fairly efficiently and therefore make the pH as normal as possible. So that would tend to fit best in that case, at least in my view. So we'll do one more case and then wrap things up. This is a young, eight-month-old female spayed golden retriever that was referred to us after having been apparently having a routine spay. She apparently fell off the recovery table and hit her head. And when she started to recover from anesthesia, she started to seizure. She's been in a coma since surgery. And the referring veterinarian has been giving her Lasix because she has apparently also developed pulmonary edema, presuming perhaps this may be non-cardiogenic pulmonary edema from her head injury. And these are her blood gases at admission. So have fun doing some calculations here, and we'll try and get one more poll in here. Great. For those of you who said this is a mixed acid-base disturbance are correct. And as this does its calculation quickly, I can say that metal, whoever metal is, is our winner with 1,409 points, followed very closely by Stingalicious with 1,320 points and Katrina with 1,221 points. So thank you all for playing along with me on that. I'm going to just skip through some of the rest of these cases, though we can probably take a quick look here at her. So again, pretty significant alkalosis. Again, when you calculate, look at these, both of her bicarbonate CO2 are above reference point. And so we're trying to explain some sort of metabolic alkalosis that has at least started to try to compensate. So we need to do our calculation. Her CO2, sorry, her bicarbonate is 43 from 22.5 is a change of 20.5. And therefore we would be expecting a change in the CO2 of around 14.4. So her CO2 should be somewhere around 51.8 if we do that math correctly and everything is compensated. And her CO2 is actually 58.6, which is 6.9 more than it's expected. And so she has both a respiratory acidosis, presumably because her head injury and seizure activity and now her pulmonary edema is causing her to have inadequate minute ventilation. She's got a respiratory acidosis and her furosemide, aggressive furosemide therapy has probably already contributed to the development of a pretty severe metabolic alkalosis. So she didn't survive, I have to say.

acid-base balance

veterinary medicine

interpretation

physiology

internal environment

acid-base theory

Henderson-Hasselbach equation

base excess approach

Gamble-Gram

blood gas results

compensatory responses

mixed acid-base disturbances