[Applause] [Music] hello this is Eric strong from the paloalto VA and Stanford University this is the 15th lecture in this course on understanding abgs and the topic is alternative approaches to asset base analysis the learning objectives are first to be familiar with the historical background behind the three major approaches to asset base analysis and second to understand the general principles of both the base excess and Steward approaches and to be able to compare them to the traditional approach that has been presented in this course I'm going to start the lecture with a brief timeline of the evolution of our Collective thinking about asset based physiology you will see later that this is important in understanding the three General approaches to acidbase analysis that exist today as the fundamental changes that have occurred in our approach to acidbase physiology are largely a consequence of the evolving definition of what constitutes an acid and a base Modern acidbase Chemistry began in the 1880s when aranias first defined an acid as a substance that when dissolved in water produces an increased concentration of hydrogen ions around 19 00 nin combined arani's definition with farad's previous supposition that annion such as chloride are base forming and catons such as sodium are acid forming thus acidbase status wasn't determined solely by the concentration of hydrogen ions but also by a number of other common electrolytes then in 1923 the Danish physical chemist Johannes bonstead and the English physical chemist Martin Lowry independently developed the idea of protonation of bases through the deprotonation of acids thus an acid was any compound that could donate protons and the base was any compound that could accept protons it was another 25 years before Physicians began taking a serious interest in acidbase balance in human physiology and when they did they solely used the Bron dead Lowry definition of acids and bases focus on the Bron dead Lowry definition does not seem to be have been the consequence of a careful analysis as to whether it actually was even the most accurate description of physiology but may have instead been simply because it was seen as more modern than the noun in definition whatever the reason however attention became focused primarily on pac2 and the serum bicarbonate concentration as the primary determinants of arterial pH this resulted in the incorporation of the Henderson hosok equation into clinical medicine as we have reviewed earlier on in this course the Henderson hosle equation said that the pH of a liquid equals the pka of any acid and conjugate based pair plus the log of the ratio of Base concentration to acid concentration when applied to human physiology Physicians used carbonic acid and bicarbonate as a conjugate acid and base pair since it was thought to be the blood's primary buffer Henry's law was then used used to convert the concentration of carbonic acid into the solubility constant times the partial pressure of carbon dioxide subsequently this form of the equation has played a critical role in studying human physiology for the last 60 years however throughout the 1950s and 60s healthy debate erupted over just how to best apply these new Concepts to actual patients on one side where a group of Americans based in various Boston area Hospital hospitals and led by Schwarz and rman on the other side were D's astrop and sigard Anderson asop and sigard Anderson first proposed the concept of Base access as a means to diagnose asset-based disorders Schwarz en rman subsequently proposed a collection of prediction rules to evaluate the process of normal compensation and thus make accurate diagnoses this is sometimes referred to as the great transatlantic acidbase debate at this point let's compare these two approaches first I'll discuss what I refer to as the traditional approach also known as the Boston approach which is what I have been teaching so far in this course when I call it the traditional approach it's certainly not my intention to take an America Centric viewpoint but my impression is that it is the most widely utilized approach in the world and certainly in my home country of the United States as already mentioned the traditional approach is advocated by Schwarz and rman focuses on the balance between dissolved carbon dioxide and bicarbonate ion as the primary determinant of pH if there is a derangement in either carbon dioxide or bicarb the body will adjust the other in order to maintain as normal pH as possible also as already mentioned the Henderson hosel equation is key in describing the exact relationship between pH pco2 and bicarb which forms the Central Foundation for analyzing AET based disorders the traditional approach defines six or seven fundamental acid-based disorders the difference due to whether one group's elevated Gap and normal Gap metabolic acidoses into the same category a separate compensation rule for each of these was empirically derived to help determine if compensation in the presence of the primary disorder is appropriate this was discussed in detail in lecture 4 one criticism of the traditional approach is the fact that there is difficulty interpreting the bicarb concentration in isolation from respiratory disorders I personally think this criticism is irrelevant since the process of compensation makes the Barm concentration not independent from respiratory disorders at all and therefore it is neither desirable nor even possible to interpret it truly in isolation irrespective of approach taken another common criticism which I think is a little bit more valid is that it fails to invoke buffers other than bicarb as we learned in lecture two there are numerous other buffers in the body including albumin phosphate and hemoglobin an alternative approach to acidbase analysis came from Denmark and primarily advocated by sigard Anderson and ASO their approach nicknamed The Copenhagen approach also advocated for the importance of hydrogen balance and the bicarbonate buffer system however it also focused on a value called the base excess the base excess is a measure of how far the total concentration of all buffers in the blood has been changed from its normal value as a consequence of metabolic derangements in other words it is a measure of how much acid would need to be added to blood to correct its pH back to normal assuming that any respiratory disorder could be ignored more quantitatively it's the amount of acid in Mill equivalent per liter that would be needed to add it to 1 lit of plasma exposed to pco2 of 40 mm of mercury in vro in order to restore the plasma to a pH of 7.40 it's important to realize that like the annion Gap the base excess is an artificial construct that doesn't directly relate to an individual parameter of physiology in an actual person it's rather a mathematical trick designed to simplify complex chemistry into something more digestible at the bedside a normal excess is theoretically zero and frequently cited in practice as -2 to pos2 mil equivalents per liter a positive base excess is consistent with a metabolic alkalosis a negative base excess sometimes referred to as a base deficit to prevent semantic confusion is consistent with the metabolic acidosis the actual equation for the calculation of Base excess is rather cumbersome and requires simultaneous measurement of hemoglobin as this is also an important buffer ABG analyzers usually will automatically calculate the base excess sparing us the need to determine it by hand although this automatic calculation helps eliminate one of the biggest practical barriers to using base excess there was another major early criticism one that's a bit complicated to explain uh but in brief base excess is a measure of the metabolic contribution to acidbase status for just the plasma and is a measure specifically done in vro since various protein buffers exist in plasma but n uh but not the extravascular component of the extracellular compartment uh base excess may be an inaccurate measure of how much acid was necessary to truly restore the body's pH to normal in Vivo therefore an additional value called standard based excess was created to address this concern standard base excess corrects this problem by calculating the base excess with a built-in Assumption of a hemoglobin concentration of 5 G per deciliter which is cited as a value which will give an approximately accurate result in Vivo here is the commonly cited equation by which standard base EXs is calculated despite my best effort I have been unable to locate either an empirically or theoretically sound explanation for using that specific value of 5 G per deciliter of hemoglobin this is especially bizarre given the combination of the apparent arbitrary and inexact nature of the simple value of 5 G per deil with a ludicrously exact four significant figures of one of the terms in this equation that is apparently used by AGG analyzers but for whatever reason this is how the standard base excess is typically calculated as you can easily demonstrate on your own from mild to moderate asset-based Arrangements the base excess is approximately equal to the difference between the measured by carb and a normal bicarb of 24 for the next 15 years acidbase analysis didn't change too dramatically aside from a greater appreciation of the utility of the anion gap however in 1978 a dramatically new approach emerged Peter Stewart a Canadian physiologist proposed the radically new idea that human acid-based physiology is better reflected by the earlier ideas of renius and nin instead of brownstead and Lowry specifically he defined an acid as any ion that shifts the dissociation equilibrium of water to higher concentrations of hydrogen ion and lower concentrations of hydroxy ion through an extension of his reasoning he rejected the notion that serum bicarb concentration was Central to understanding acidbase disorders his system of acidbase analysis is based upon six physiologic principles or axioms first as just mentioned an acid is any species that raises hydrogen ion concentration of a solution tion second the quantity of hydrogen ion added or removed from a physiologic system is not relevant to the final pH since the hydrogen ion concentration is a dependent variable third human plasma consists of fully dissociated strong ions such as sodium potassium chloride and lactate partially dissociated weak acids such as albumin and phosphate and volatile buffers such as carbonate species fourth an evaluation of nonvolatile buffer equilibrium is important to the description of acidbase balance fifth the weak acids of plasma can be described as a pseudo monoprotonic acid ha and finally sixth plasma membranes may be permeable to strong ions and therefore transport of strong ions across cell membranes May influence hydrogen ion concentration using these physiological princi IES he defined six simultaneous equations that he believed dictated a patient's asset based status I won't review them individually but we summarize by stating Stuart found a rather complicated fourth order polinomial solution for the system of equations which luckily can be simplified as this in most situations you will note that the steart equation shares a similar form as the Henderson hobok equation as adapted for acidbase balance however instead of including two independent variables bicarbonate concentration and pco2 there are now three Sid a total and the familiar pco2 K Suba is an equilibrium constant and the S is the solubility constant for carbon dioxide in water let's take a closer look at these three independent variables first is the Sid which stands for strong ion difference this is the difference between completely dissociated cations and completely dissociated anion the term strong here refers to how strongly the ions dissociate and not how concentrated the solution is in practice there are different subtypes of the strong ion difference for example Sid Suba for Sid apparent is used to simplify the fact that numerous minor strong ions are not typically measured but which collectively contribute very little to this calculation unfortunately there are a number of variations of the Sid sub a calculation that are used in practice this here is just one such variation Sid sub is normally cited to be 38 to 42 M equivalents per liter but it depends slightly on the specific calculation used a total is the plasma concentration of nonvolatile weak acids which only partially dis associate such as phosphate and albumin in the absence of unmeasured anion a total should approximately equal the traditional annion gap finally pco2 is the partial pressure of carbon dioxide in arterial blood just the same as it is in the traditional and Copenhagen approaches there are two other important variables in the steward approach first Sid sub which stands for Sid effective represents the sum of the plasma buffers as with Sid sub a there are several variations of this calculation here's one where Sid sub E equals the bicarb concentration plus the concentration of ionized albumin plus the concentration of ionized phosphate the latter two can be estimated from empirically derived equations listed here second the strong ion gap or Sig is an estimate of the unmeasured annion in plasma and resembles the traditional annion Gap except its normal value is zero it is mathematically equal to Sid a minus Sid e Stewart's approach creates six primary acidbase disorders first are respiratory acidosis and alkalosis which are the same as in the traditional approach with the exception that it ignores compensation and thus does not subdivide them into acute and chronic processes next is a Sid acidosis which is characterized by a low Sid a with a Sig of zero this represents most conditions traditionally referred to as normal Anon Gap metabolic acidoses then is a Sig acidosis which is characterized by an elevated Sig with normal Sid a this represents most conditions traditionally referred to as elevated an Gap metabolic acidoses both Sid and Sig acidoses are subtypes of of strong ion acidosis which are all characterized by a low Sid e the next class of disorders is strong ion alkalosis characterized by an elevated Sid e with an elevated Sid a and normal Sig these represent conditions traditionally referred to as metabolic alkalosis next is nonvolatile buffer acidosis characterized by an elevated a total examples include hyper albuminemia and hyperphosphatemia finally is nonvolatile buffer alkalosis characterized by low a total as would be seen in hypo albuminemia there is no correlate to the nonvolatile buffer acidosis and alkalosis in the traditional and Copenhagen model the difference between the strong ion acidoses can be a bit confusing so I'm going to clarify them a little with some diagrams this will be most clear if I start with something a little more familiar like the difference between a normal and an elevated an Gap acidosis which was discussed in detail in lecture 5 here is a representation of normal ions in Blood on the left are positively charged cat ions and on the right are negatively charged anion the anion gap is typically defined as the difference between sodium and the sum of bicarb and chloride in this particular example the acidbase status is normal and thus the an Gap is equal to 12 in the next example there is a deficiency of bicarb and an excess of chloride such that the total of the two remains constant thus the an Gap is the same this is what is seen with a normal Gap metabolic acidosis in the last group The bicarb is again low but instead of excess chloride there is an excess of unmeasured anion as a consequence the annion Gap is elevated and thus this is referred to as an elevated Gap metabolic acidosis the difference between a Sid and a Sig acidosis is very similar we'll start with the ion concentrations seen in a patient with normal acid based status the Stuart model places greater emphasis on the specific concentrations of albumin and phosphate so we will include the negatively charged proportion of these molecules in our analysis to remind you there are several similar equations used for the calculation of Sid a but it is approximately equal to sodium plus potassium minus chloride shown here Sid e also has several equations but is commonly calculated as bicarb plus negatively charged albumin plus negatively charged phosphate Sid e is shown here the strong ion Gap is Sid a minus Sid e which as you can see from the diagram is approximately zero in the next example bicarb is low and chloride is high if we label our Sid a and Sid e we will immediately see that the Sig is zero thus this is a sid acidosis which is practically speaking the equivalent of a normal anion gap acidosis in the last example bicarb is low and unmeasured annion are high here is Sid a which is sodium plus potassium minus chloride and here is said e which is bicarb Plus L charged albumin plus negatively charged phosphate these two values are no longer equal the difference being the strong ion Gap or Sig thus this is a Sig acidosis which is analogous to an elevated an Gap acidosis you can also observe that in both the Sid and Sig acidoses the Sid e is reduced which is the consistent Hallmark of a strong ion acidosis in general to further compare different approaches to acid-based physiology I want to look at a very brief qualitative analysis of a simple physiologic phenomenon gastric acid secretion in the stomach the traditional approach is based on the Henderson hous boach equation in this model secretion of hydrogen ions into the stomach Lumin by parietal cells shifts the equilibrium between bicarbonate ion and carbonic acid towards the ladder this lowers the concentration of bicarbonate ion which by the Henderson hosbach equation must result in the lower pH of the gastric Lumin in the steward approach a more complete version of the calculation for apparent strong ion difference states that it is equal to the sum of charges from sodium potassium calcium and magnesium all minus the sum of charges from chloride and lactate thus it is actually secretion of chloride ion as the other half of hydrochloric acid that is important increasing the concentration of chloride in the gastric Lumen lowers the strong ion difference and it is this effect that lowers pH by virtue of the steward equation we saw earlier I've presented a lot of information in this lecture so far much of which will be completely unfamiliar to most viewers therefore I'll summarize the lecture by presenting a comparison of the different approaches to acidbase physiology in this chart those three approaches to remind you are first the phys logic approach colloquially referred to as the Boston approach and which I commonly refer to as the traditional approach which is what the previous 14 lectures have covered next is the base excess approach colloquially referred to as the Copenhagen approach finally is the steward approach which is more forly referred to as the strong ion or physiochemical approach starting with the physiological or traditional approach it invokes the Bron onstead Lowry theory of acids and bases the bicarbonate buffer system is Central to the approach the principal variables it focuses on are pco2 serum bicarb concentration and the annion Gap depending on how one desdes to subdivide them there are anywhere from four to seven General types of acidbase disorders including acute and chronic respiratory acidosis acute and chronic respiratory alkalosis normal or elevated an Gap metabolic acidoses and metabolic alkalosis historically the major proponents of this approach have been Americans most notably William Schwarz and Arnold rman moving on to the base excess approach this is also based on the Bron dead Lowry theory of acid base and the bicar buffer system is also Central the principal variables are pco2 base excess and N Gap The General types of acid-based disorders that it defines are the same as above and the major proponents of this have historically been Europeans specifically sigard Anderson and ASO from Denmark from this basic chart you can see that on a fundamental level the traditional approach and the base acccess approach are very similar finally in the steward approach the invoked theory of acids and bases is that of arus and nin bicarbonate is considered to be a dependent variable and thus its importance in the approach is minimal instead the principal variables are pco2 strong ion difference and total concentration of weak acids there are six to seven General types of acid-based disorders in the steward approach respiratory acidosis and alkalosis strong ion acidosis which can be subdivided into low Sid a or high Sig acidosis strong ion alkalosis and nonvolatile buffer acidosis and alkalosis as a general rule the steid approach does not usually consider metabolic compensation for chronic respiratory disorders for example in the traditional model the presence of a chronic respiratory acidosis would induce kidneys to excrete hydrogen and hold on to bicarbonate as part of metabolic compensation which would not be considered a separate acidbase disorder per se however in the Stuart model this mechanism would be looked at as a reabsorption of sodium out of proportional to Chloride which would increase the strong iron difference and which would lead to a primary strong ion alkalosis that would be a separate acidbase disorder from the respiratory acidosis that triggered it finally as its very name implies the originator and strongest proponent of the Stewart approach is of course Peter Stewart himself up until now everything I have reviewed in this particular lecture has been relatively qualitative and theoretical this is in contrast to the previous 14 lectures which have been heavily practical in nature so you might rightly be wondering how do these other approaches translate into a practical bedside analysis that is what is the algorithm for applying these approaches to an actual patient unfortunately there are no Universal and standardized Al algorithms during this course I have presented the most thorough version of the traditional algorithm that comes closest to being Universal and standardized but in reality there is still much variation from institution to institution and from country to country while algorithms based on base excess generally reach the same conclusion as those based on the Boston or traditional approach there is even more variation in the sequence of steps taken and the thoroughness with which the analysis is carried out finally there is absolutely no standardized algorithm that utilizes the steward approach in preparation for this lecture I reviewed about two dozen papers websites and textbooks that discuss the steward approach two3 of these sources discussed the steward approach only a mathematically heavy physiochemical analysis that was far removed from actual patients and of the remaining one-third of sources every single one used a practical algorithm that was marketly different from the others at this point I'm going to present a real world example of an acidbase disturbance as identified by an ABG and demonstrate how one might use the three different approaches to diagnose the underlying abnormality a 35-year-old woman presents with two days of fevers chills and a malays her vitals revealed a temperature of 103° fah heart rate of 135 blood pressure of 78 over 40 respiratory rate of 30 and oxygen saturation of 97% on room air her ABG basic metabolic panel and albumin are as follows how would one use the Boston or traditional approach to analyze this situation step one check the pH she's obviously acidemic step two check the pco2 since the PCO 2 is low and that is deranged in the same direction as her pH the acidemia is caused by a metabolic acidosis step three evaluate compensation for a metabolic acidosis we would use Winter's formula and ask if the pco2 is approximately equal to 1.5 * bicarb + 8 in this case this is true so therefore compensation is appropriate step four calculate the anion gap which is sodium minus the sum of chloride and bicarb which in this case is 18 and we then adjust the Anon gap for hypo albuminemia to determine an adjusted gap of 23 thus the metabolic acidosis is an elevated an Gap metabolic acidosis then step five since the Anon Gap is elevated we calculate the Delta ratio as reviewed in lecture six this is equal to the change in N Gap from normal divid by the change in bicarb from normal for this patient this works out to be 11 / 9 or 1.2 since the patient probably has lactic acidosis a Delta ratio between one and two is what we would expect to see and thus there is no additional acidbase disorder present thus our final acidbase diagnosis is a simple elevated n Gap metabolic acidosis how would we use the Copenhagen or base access approach for the same patient Step One is the same low PH equals acidemia step two would be to calculate the standard base excess now there are a couple of equations in a literature on how to do this as mentioned before this is the most commonly cited one with the patients values already inputed which gives a standard based excess of 9.8 luckily most ABG analyzers will calculate this for you a negative base excess which is sometimes referred to as a base deficit means that the patient has a metabolic acidosis as with the former approach the next step is to evaluate compensation the base excess approach also has a collection of empirically derived compensation rules for the various acidbase disorders for a metabolic acidosis the pco2 should be lowered by about 1 mm of mercury for every 1 mil equivalent per liter That Base excess is below zero since that is indeed the case here compensation is appropriate the next step is calculating the an Gap and adjusting for albumin I haven't included the Delta ratio here since in my experience most users of the base excess approach generally don't bother with it but there is no reason one couldn't calculate the Delta ratio either by using the Delta by carb or with a slight adjust adjustment in the equation to use the Delta standard based excess the final conclusion is the same in elevated an Gap metabolic acidosis and from watching these steps you can further appreciate that on a fundamental level the traditional and base excess approaches are nearly identical but how could you use the steward approach remember that there is no remotely standardized algorithm to applying the steward approach to real world bedside assd base analysis however the following is a representation of an algorithm one could potentially use step one calculate the total concentration of ionized weak nonvolatile acids this would approximately be equal to the sum of ionized albumin ionized globulin and ionized inorganic phosphate each of these can be calculated by a separate equation utilizing separate constants relating the pH to the proportion of the specific molecules that are ionized as you can imagine this is extremely cumbersome but take my word for it that for this patient assuming normal levels of globulin and phosphate the net nonvolatile acid concentration is about 5 milles per liter for step two you would calculate the effective strong ion difference this is equal to the bicarb concentration plus a total which is 20 since 20 is below the normal range of Sid e of 38 to 42 this patient has a strong ion acidosis step three calculate a parent Sid which depending upon one's preferred calculation is approximately sodium plus potassium minus chloride 120 - 4 + 87 is 37 which is nearly normal as Sid a should also be about 38 to 42 finally for step four calculate the strong ion gap which is Sid a minus s e which is 17 as Sig should be zero this patient has an elevated ated strong ion gradient so we would diagnose this as an elevated strong ion gradient acidosis with this example which is actually a rather straightforward acidbase abnormality you will probably find the steward approach to seem unfamiliar non-intuitive and cumbersome especially with a calculation of a total which really cannot be done efficiently without the aid of an application specifically designed for this while I certainly do not mean this as a criticism of the man himself I think it's relevant that Peter Stewart wasn't a physician but rather a physiologist for him the lab may be the perfect setting in which he could apply his physiochemical model to work through problems in human pathophysiology however after working through examples like this myself I find it difficult to believe that many people who prefer the steward approach are routinely in the position of needing to diagnosed acid-based disturbances in real time at the bedside of critically ill patients and as an analogy I imagine two people playing a game of Billiards and on a particularly difficult shot one decides to use the Schrodinger wave equation to calculate the appropriate angle and speed with which the Q ball should be struck while a person could technically use quantum mechanics to successfully play Billiards there would be no benefit over simple Newtonian physics that could be estimated in one's head and the quantum mechanics calculations would take so long that the opponent might forfeit on account of boredom at this point I was originally going to review literature evidence that fails to find any measurable benefit of the steward approach in clinical situations but the lecture is already running a bit long so I will spare you however more compelling than this would have been is the conclusions of one particular paper probably the most rigorous critical review of the steward approach that took an in-depth look at the steward equation to remind you this equation is the final result of Peter Stewart's complex analysis of human asset-based physiology that was based on his six postulates and six equations of equilibrium and conservation what this paper proved was that the numerator of this fraction is in fact mathematically equal to the serum bicarbonate concentration therefore the Stuart equation is nothing more than a dressed up version of the Henderson hasselbach equation for the bicarbonate buffer system the same equation that Stuart criticized as non-physiologic in conclusion the traditional and base excess approaches are based on similar principles and generally result in identical diagnoses provided that the N Gap is corrected for albumin there is no significant benefit of the stward approach in actual practice and given its lack of clinical benefits lack of General familiarity and it significantly increased complexity routine use of the steward approach in clinical medicine is not recommended despite the rather strong way I've ended this lecture the steward approach definitely has its Advocates and it remains quite a controversial and polarizing Topic in critical care medicine therefore I think it's appropriate to finish with the following two quotes Peter Stewart once said of the traditional bicarbonate centered approach it is cluttered with jargon chemically meaningless derived quantities a misunderstanding of what is happening and an artificial use of the Henderson hosbach equation as a single equation determining acid base balance in any fluid while sigard Anderson has said in response the steward approach is absurd and anachronistic I hope you have found this lecture to be interesting and useful the next four lectures will shift focus of ABG analysis from acidbase balance to oxygenation [Music]