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Approach to Acid Base Status: Step 4 – Laboratory Diagnostics

by Carlo Raj, MD

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    00:01 Approach to acid base. Well, now, we're getting into specifically metabolic acidosis.

    00:07 Keep that in mind.

    00:08 So, for metabolic acidosis, you will calculate the anion gap.

    00:11 This is what you wanna know clinically and this is what you stick with.

    00:14 And do not, I repeat, do not for the sake of time, use anion gap for metabolic alkalosis.

    00:20 That will drive you crazy. Metabolic and it's really no need.

    00:23 Metabolic acidosis, I'm gonna explain what this anion gap means.

    00:27 I'll show you graphs and pictures and then, we'll go one step further.

    00:30 We already discussed where your cation, sodium, you're not using potassium, negligible, 3.5 to 5.0 potassium, negligible.

    00:41 And you have your anions, chloride and bicarb.

    00:44 Normal anion gap, 10 to 14, you can use 10 as a point of reference.

    00:50 Next, what would you have to do clinically? You know so many conditions in which your patient could actually present with hypoalbuminemia.

    01:01 So, many, yes, you do. You know nephrotic disorders and you also know about liver damage.

    01:07 Is that pretty major in terms of society? Sure, it is.

    01:11 Now, what type of charge does a protein have? Negative charge.

    01:17 So, therefore, for every one milligram deciliter below four, you will subtract three to normal anion gap.

    01:26 By normal anion gap, we mean approximately 10.

    01:29 So, you have to clinically then correct for hypoalbuminemia if need be if that is a patient who has something like cirrhosis, something like nephrotic disorder and the question is asking you about metabolic acidosis and to please figure out the anion gap.

    01:47 What else do you wanna do? Well, this is the unmeasured anions and the unmeasured cation, the sodium.

    01:55 You rearrange the formula, you end up getting your anion gap which is normal, approximately 10.

    02:01 What does it all mean? Let me set this out for you.

    02:05 On your left, all cation that you will use.

    02:09 Shall I say, the only cation that you use clinically is a sodium of 140, 145, what have you.

    02:16 Okay, so, that's my cation. What must always exist in your body as a measure of homeostasis? Electroneutrality. So, whatever positive charges you have, you have to be able to equate that the negative charges.

    02:31 It is that simple. So, opposites will attract. So, let's add this up, shall we? So, we got 140 of sodium, what is that? Cation.

    02:39 We have chloride between 95 to 105, we have an anion of 105, chloride.

    02:45 So, now, we have a difference of how much? Thirty-five.

    02:49 See, if you add up all your anions, well, now, you have 25 and what are your anions in the formula? Take a look, chloride plus bicarb.

    02:58 Well, that then adds up to, well, we have 130, what's your anion gap? Ten.

    03:05 Is that normal? Absolutely, absolutely. So, the unmeasured anions of 10 is perfectly normal.

    03:12 So, what are they? That's your protein. By proteins, I don't mean albumin.

    03:15 And so, therefore, there will be like sulfates, and phosphates, organic anions, so, then, with these will then contribute to that non- anion gap.

    03:24 In other words, excess anions. Normally, about 10.

    03:28 Well, what does this mean in terms of moving above 10? Well, take a look.

    03:32 Say that you have a patient who's exercising and when they exercise excessively, is it possible that you start feeling cramps and pain in your muscles? Ow. Well, what does that mean to you? That means that you are now shifting from aerobic to anaerobic glycolysis, aren't you? As you shift into anaerobic glycolysis, then, would you produce more of and less of? Less of ATP, then, you produce more lactic acid.

    03:59 So, lactic acid build up in your muscles then gives you that cramp, doesn't it? Sure, it does.

    04:04 Another big topic as well is if there's just straight up ischemia.

    04:08 Anytime there's ischemia, you know that there's an increase in lactic acid.

    04:11 To begin with, when would you even consider doing anion gap? Metabolic acidosis.

    04:16 What is lactic acidosis? The metabolic acidosis. So, now, you do an anion gap.

    04:22 You find your cation of 140, as your anions while the board gives you something like your bicarb of 10 and a chloride of 105, what do you get? You get a measly 115. So, you get 115, so, what is your anion gap at this point? 140 minus 115, I do believe that that is your 25, isn't it? Okay, so, you got a 25 there as being your anion gap. What's normal? Approximately 10.

    04:50 What accounts for 15 additional anion gap? The lactate.

    04:56 An example, here you go, of anion gap, metabolic acidosis in fact is lactic acidosis.

    05:03 Can you replace that lactic with ketones? Sure, you can. What do you end up getting? Diabetic acidosis, don't you? Keep this picture in your head as far as the electrolytes that are responsible for contributing to anion gap because we will have to go one step further and another step further, and another step further so that you get every single perspective of anything that's thrown at you absolutely correct.

    05:27 The more knowledge that you have, the more aware that you know things exist, the less you will be confused, right? But be careful though, you also have to have a firm understanding.

    05:35 Let's move on. So, elevated anion gap refers to increase in unmeasured anions.

    05:41 These include ketones or lactate. I just had shown you a picture.

    05:46 Step four, read this, for elevated anion gap metabolic acidosis.

    05:55 AG stands for anion gap, MA, when would you only use anion gap, please? Good, metabolic acidosis.

    06:02 So, when you're using this step, if you need to, remember, every step of the way, you're asking yourself this question, have I answered the question? Have I answered the question? Have I come to the proper conclusion about my patient? If you have, then, step away, you've done your job. Let's move on to the next one.

    06:19 Here you said that you haven't and you're doing anion gap metabolic acidosis, that's what you have.

    06:25 Give yourself an example such as lactic acid or DKA. We'll go through differential.

    06:30 Big time, we've talked about some of that. The mnemonic that you may use such as MUDPILES. Right? We talked about methanol, we talked about uremia, so on and so forth.

    06:40 So, those are your differentials. Check urine ketones and if not present, check renal function, lactate, toxin screen, and osmolal gap, what does that mean? Please give me two ways in which a patient can develop metabolic acidosis, two ways, keep it simple.

    06:59 Endogenous, within the body, exogenous, you're consuming it.

    07:04 Endogenous, I just talked to you about exercise, what are you producing? Good, lactic acid.

    07:10 What is that? An anion gap metabolic acidosis. What about diabetic ketoacidosis? That is also what? An anion gap metabolic acidosis. Where is the origin of that? Good, endogenously.

    07:24 What if you were consuming an acid? What do you mean? Such as ethylene glycol, such as methanol, such as salicylate.

    07:33 So, exogenous sources. Now, what can you possibly do mathematically and clinically so that you -- if you can figure out how is it that the patient has developed an elevated anion gap metabolic acidosis. Understand something here.

    07:50 Whenever you're given a piece of information of anion gap that automatically puts in the realm of above 10, maybe 25, maybe 30.

    07:58 What if it says non-anion gap? That means normal which is not our discussion yet, not yet.

    08:04 Keep in mind the big picture. But what is the osmolal gap? It is the measured osmolality subtracted from the calculated osmolality.

    08:13 For example, the calculated osmolality is going to be, wow, you've come back to that interesting formula that we called effective osmolality.

    08:21 And what is effective osmolality to you mean? Two times sodium plus your glucose over 18.

    08:27 Don't forget that. What about Blood Urine Nitrogen? Let it go for now.

    08:31 That's not part of the effective osmolality. So, that is your calculated and measured.

    08:36 So, for example, let's say that your calculated osmolality was approximately 300.

    08:41 So, now, let's say that your osmolal gap is greater than 10. If your osmolal gap is greater than 10, guess where this anion gap is coming from? Possibility of ingestion of cause of anion gap metabolic acidosis.

    08:56 So, we find that the osmolal gap is increased between the measured and calculated, guess what? You have most likely confirmed or highly now suspect that there's going to be an ingestion of anion gap metabolic acidosis.

    09:12 Interesting, isn't it? So, this might then give you a differential of, well, huh, exogenous, now, you're looking for sources.

    09:19 What exactly did your patient consume? Was it ethaline glycol? Was it methanol? Was it alcohol? Was it some type of drug? Was it iron? So on and so forth. Let's continue.

    09:30 Now, I'm gonna go through this efficiently. It's just enough where you have enough information.

    09:36 So, at this point, you have absolutely diagnosed elevated anion gap metabolic acidosis.

    09:42 You have now figured out that this patient has exogenously taken some kind of acid so therefore, you got an increase in osmolal gap.

    09:51 Is there a possibility that your patient has an anion gap metabolic acidosis along with a mixed non-anion gap? True, so, therefore, this brings us to an interesting concept called the delta gap.

    10:06 All that I wish to point out to you based on feedback that I've gotten making sure that I give you everything that you need for proper tools. Let's begin.

    10:16 Calculate, patient's anion gap. But we already know the patient has an anion gap metabolic acidosis, so, that will be given. You'll know or you've calculated it.

    10:26 And then, from this, you subtract your normal anion gap. That literally means your delta gap.

    10:32 What the heck does that even mean? That means if the change in bicarb, remember that picture that I just showed you.

    10:38 I asked you to please conceptualize and keep that bar graph of sodium on one side of 140 or the two anions on the other side, your bicarb and chloride which gave you the original, well, there, that gave you approximately 125, and so, therefore, or 130 should I say, excuse me, 130, and we had a normal anion gap of 10, right? So, everything equaled out. That was normal.

    11:03 And I told you in our next figure that if that, well, you started adding in lactate, you were taking away what? Bicarb.

    11:12 And you already know in metabolic acidosis that your bicarb is decreased.

    11:16 My point is this. Is that change in bicarb, is that change in bicarb enough or sufficient to properly explain the change in anion gap? This will then give you delta gap. Let's take a look. Compared to change in bicarb, what does that mean? Once again, who is your patient so far? Metabolic acidosis anion gap.

    11:40 Where'd that anion gap come from? The osmolal gap would tell you most likely if it is going to be exogenous or endogenous.

    11:48 Greater than 10? Exogenous. Stop there.

    11:51 So, now, we have anion gap metabolic acidosis and now, you wanna see as to whether or not there's an underlying issue.

    11:59 The underlying issue here is going to be, well, is the change in bicarb equal to the change in anion gap? If those two equal out, then, you know that your patient has normal change and it is strictly an anion gap metabolic acidosis with no mixed underlying issue.

    12:17 Let's take a look at a few. Example, a bicarb of 16, stop there. Normal bicarb, about 24? We'll use 24. Drop down to 16, so far, very clear that we have metabolic acidosis.

    12:34 Remember it, this entire topic is anion gap metabolic acidosis.

    12:38 So, all I wanna do is make sure that we're on the same page.

    12:41 There's an anion gap of 20. Either they gave it to you or you figured it out. How did you do that? Sodium minus your anions. Okay, normal anion gap is 10.

    12:54 But here, we have 20, so, this is definitely an anion gap metabolic acidosis.

    12:59 Next, let's say your normal anion gap is about 12.

    13:03 Now, we take the difference, the absolute difference of 20 and 12, we get eight unmeasured anions.

    13:13 Okay, let me stop you there. If there's a change of eight unmeasured anions and you're thinking about that graph, the bar graph that I showed you with the cations obviously were on the side of the anions and if there's a change of eight, what kind of change should we find in bicarb? Eight.

    13:34 If both of these are equal, then, it is a pure anion gap metabolic acidosis with no underlying disease.

    13:44 What is this called? A delta gap.

    13:47 Now, before any of this, obviously, you did your degree of compensation and by that, we mean if it was metabolic acidosis and that respiratory compensation, what was that respiratory compensation in metabolic acidosis? A decrease in bicarb should equal a decrease in carbon dioxide.

    14:04 So, that step was already done by you and that's in the initial stages.

    14:07 So, normal bicarb, 24, the patient's bicarb, 16. What's the absolute difference? Eight.

    14:16 There is the change in bicarb equal to the anion gap change. Yes, it is.

    14:21 So, therefore, what's my diagnosis? A pure anion gap metabolic acidosis.

    14:28 Now, if the change is greater than the change in bicarb, it's a concomitant metabolic alkalosis.

    14:36 Let me show you something as we move through here as an example.

    14:39 If the change in anion gap is less than bicarb, then, it's a concomitant non or normal anion gap metabolic acidosis.

    14:48 Stop there. Now, I'm gonna show you something so this makes better sense.

    14:52 For example, let's do this one. A bicarb of 10, normally, about 24.

    14:59 So, we have metabolic acidosis, okay.

    15:02 Anion gap of 20, either you calculated or they've given it to you and so, therefore we have, what's my diagnosis? Obviously, anion gap metabolic acidosis. Let's do the change in anion gap.

    15:15 We get eight. Stop there. Now what? Well, we should find a change of bicarb being eight.

    15:23 Let's see whether or not that has taken place.

    15:26 Normal bicarb of 24 and the patient's bicarb is 10, what's the absolute difference? Fourteen.

    15:33 Uh-oh, the unmeasured anions, anion gap does not add up to the change in bicarb, you see this.

    15:43 Wow, so, what's happening? There's a difference of how much there? There's a difference of six, isn't there? Eight and 14. So, the six means what? It's unaccounted for.

    15:54 So, the fact that you do not find an anion gap which explains this, there must be an underlying issue.

    16:02 What is that underlying issue? Here, you'll notice.

    16:05 Now, go back to the previous discussion that we just had about anion gap being less than.

    16:10 If the anion gap, the eight is less than the change in the bicarb, then, this to you gives you a combined diagnosis of anion gap and non-ion gap metabolic acidosis.

    16:26 This is as tricky as they will get. I wish to introduce the concepts to you.

    16:32 If I were you, I will go through the first few steps where you figure out the pH, you figure out the primary, you figure out the degree of compensation.

    16:41 If need be for metabolic acidosis, you do an anion gap.

    16:46 With anion gap, you then figure out if it's exogenous or endogenous.

    16:51 It would be who of you to make sure you pay attention to the osmolal gap.

    16:55 Once you get as far as that, maybe perhaps, you'd take a look at delta gap if need be.

    17:01 Most of your questions will be answered as far as what I've taken you.

    17:06 Now, if it is respiratory and it's renal compensation, what would you wanna know about that? It could have an acute and chronic change. Let's continue.

    17:16 So, for a normal anion gap, that the only thing that we're left with now.

    17:20 With the normal anion gap, what are you trying to do? Well, this is interesting as well.

    17:24 With the normal anion gap metabolic acidosis, you know that there is no anion gap.

    17:31 Meaning to say or in other words, really, it's within normal limit, okay? So, what does that mean to you? Well, check urine anion gap. Why? Because you don't know as to whether or not that bicarb is being lost through the urine or if the bicarb is lost where? Through the intestine. For example, think diarrhea. When you have diarrhea, what happens? You lose bicarb. It has nothing to do with the urine.

    18:01 So, your non- anion gap metabolic acidosis by using clinically a urine anion gap will then give you how your patients lost their bicarb, sound beautiful? Well, not so much for the patient but for you.

    18:14 Urine sodium plus urine potassium from this, you subtract your urine chloride. Stop there.

    18:21 The first time that we're seeing potassium in the urine, it is significant.

    18:25 And why not bicarb, why isn't bicarb here? Because that's what you're trying to figure out.

    18:29 If the urine anion gap is positive, think of it as being positively getting rid of bicarb.

    18:36 You wanna think of potential causes such as renal tubular acidosis type two.

    18:42 And renal -- type two wasn't a problem. Where was it? Two lines to make an X, proximal convoluted tubule is type two RTA.

    18:51 What could be a potential problem? Oh, carbonic anhydrase inhibition.

    18:55 So, therefore, your anion gap will be positive for bicarb. What if you do the formula and the urine anion gap is negative? Now, what do you get? Well, this means that the bicarb is not being lost from the urine.

    19:10 In fact, it's being lost where? Through the GI tract. Welcome to diarrhea.

    19:16 This is for non-anion gap metabolic acidosis. This is all for what? Metabolic acidosis.

    19:22 You see as to how important it is for you to absolutely do the anion gap.

    19:26 It's gonna put you into two major families of differentials.


    About the Lecture

    The lecture Approach to Acid Base Status: Step 4 – Laboratory Diagnostics by Carlo Raj, MD is from the course Pulmonary Diagnostics.


    Included Quiz Questions

    1. 10-14
    2. 12-18
    3. 11-24
    4. 60
    5. 40
    1. For every 1 mg/dL below 4, subtract 3.
    2. For every 2 mg/dL below 4, subtract 3.
    3. For every 1 mg/dL below 4, add 3.
    4. For every 1 mg/dL below 4, divide by 3.
    5. For every 1 mg/dL below 3, subtract 3.
    1. Plasma magnesium is included in the formula.
    2. Anion gap = unmeasured anions - unmeasured cations
    3. Anion gap = Na - (Cl + HCO3)
    4. May include organic anions and proteins.
    5. It is influenced by albumin levels.
    1. 50
    2. 35
    3. 15
    4. 10
    5. 24
    1. Ketones
    2. Lactic acid
    3. Pyruvate
    4. Salicylic acid
    5. Hydrochloric acid
    1. Measured Osmolality - Calculated Osmolality
    2. Urine Osmolality - Serum Osmolality
    3. Calculated Osmolality - Measured Osmolality
    4. Serum sodium - (Serum bicarbonate + Serum chloride)
    5. 2 x (Na) + (glucose) + (urea)
    1. Osmolar gap > 10
    2. Osmolar gap < 10
    3. Elevated ketones in the urine.
    4. Increased blood urea nitrogen.
    5. Anion gap > 20
    1. Change in HCO3 = Change in the anion gap.
    2. Change in HCO3 > Change in the anion gap.
    3. Change in HCO3 < Change in the anion gap.
    4. Change in the delta gap = Change in the anion gap.
    5. Change in the delta gap > Change in the anion gap.
    1. 2 (Na+) + Glucose/18 + BUN/2.8
    2. 2 (Na+) + Glucose/18 + BUN/2
    3. 2 (Na+) + Glucose/8 + BUN/2.8
    4. 2 (Na+) + Glucose/18 + Uric acid/2.8
    5. 2 (HCO3) + Glucose/18 + BUN/2.8
    1. Patient's anion gap - Normal anion gap
    2. Patient's cation gap - Normal anion gap
    3. Patient's anion gap - Normal cation gap
    4. Patient's anion gap - Urine anion gap

    Author of lecture Approach to Acid Base Status: Step 4 – Laboratory Diagnostics

     Carlo Raj, MD

    Carlo Raj, MD


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