Complex acid-base derangements. So, who's excited about that after lunch? It's going to put us to sleep. Okay. So, again, we cannot cover all of this and I'm not going to be able to give you a whole problem set of like 30 different problems that you can work your way through. So, just review metabolic acidosis, including anti-GAP and non-anti-GAP, and then I'm going to talk a little bit about alkalosis and maybe a little bit about respiratory acidosis and as such. But just remember that we have this balance between acid generation, we're always generating acid, and then we need to be excreting acid, and we excrete acid in our urine, and we excrete volatile acids through our respiratory system. So, if we can't excrete the acids well in the urine for whatever reason or if we can't excrete our volatile acids, we're going to become acidemic or if we have an overproduction of acid. Make sense? Okay. All right. What about how do we evaluate this stuff? So, the first thing is that we have to make sure we do a good history and physical, right? We need to understand what are the potential issues that could be contributing to this. Are they having diarrhea? Are they vomiting? Are their kidneys working? Are their lungs working? Are they breathing? Is their brain working? All of these things are going to impact our acid-base status. So, in your labs, the values between 7.35 to 7.45 are going to show up as black, and they're going to be viewed as normal. On the board exams, if the pH is not exactly 7.40, then you need to start thinking about acid-base problems, because they may be asking you that. So, if it's 7.39, you need to start doing all of your calculations and see if it's a metabolic acidosis with respiratory compromise or whatever, because they're going to stump you on some of those. All right. Anion gap and unmeasured anions. So, electroneutrality, we have to have our anions equal our cations, right? It makes sense. But we don't measure all of our cations and we don't measure all of our anions, and that's what makes up our anion gap. We don't walk around with an anion gap. We are electrically neutral, but we're not measuring those all. Does that make sense? So, normal is not 12 to 14. Normal with modern equipment is 10, maybe up to 12. The vast majority of the unmeasured anions is albumin. So, when albumin level is low, then what the expected anion gap would be if everything else is normal is also going to go down. Does that make sense? So, if you had zero albumin, then you should have zero anion gap. Make sense? Because that's the vast majority of it. We're pretty close. All right. You've got phosphorus and a few other things, sulfuric acids and some other stuff that we don't measure in there. Okay. I mentioned that in there, unmeasured cations. We do actually measure potassium, calcium, magnesium. We don't measure immunoglobulins, right? But we don't factor those in to our anion gap because sodium is, by far, the most dominant cation, right? Okay. Serum anion gap, albumin, I already talked about this. Yeah. So, your albumin, your anion gap is going to reflect your albumin level. If you want to estimate that, the expected anion gap, if everything else is normal, should be two and a half to three times your measured serum albumin level. So, if your serum albumin level is two, then your anion gap, if everything else is normal, your expected anion gap should be five to six. So, if it's nine, then that patient has an anion gap metabolic acidosis. Okay. So, you really have to look at that. I know they calculate your anion gap on your EMER, but you really got to look down and see what the albumin level is to help you know if it's correct or not. Okay. By far, the most common cause of anion gap acidosis are lactates, right? Or lactic acid. I think you guys know that. Let's see what else was on this slide. Yeah. It's by far the most common cause, okay? In the ICU. I'm trying to remind myself here. Okay. So, how do we work our way through this? So, one milliequivalent per liter of acid added to the circulation should change the bicarbonate by one, and the anion gap should go up by one. Okay. So, if you make sure your delta bicarb by your delta anion gap, it should be about one. Okay. Delta delta or delta bicarb divided by delta, or anion gap divided by delta bicarb is calculated here, in which you have your expected anion gap. I think this is a little bit too complex for rounds. Okay. So, the way to do this in a more easier and quick way on the boards is to look at what your albumin level is and calculate out what your expected anion gap should be. So, let's say you expect it to be five. You've measured nine. Okay. So, now your delta anion gap is four, right? Look at your bicarbonate. If your bicarbonate has changed by four, then everything is hunky-dory. Okay. If it's gone from 24 to 20. If your bicarbonate has gone from 24 to 12, your bicarbonate has changed much more than your anion gap has changed. So, therefore, there's got to be some sort of non-anion gap process that's chewing up bicarbonate. Does that make sense? Okay. So, on the boards, it's much easier to not do math and to think about it conceptually. All right. Lactic acidosis. So, again, it's the most common cause. There's the L isomer and the D isomer. I think we sometimes get a little bit wishy-washy on this. D is lactate is very uncommon, okay? What's much more common is going to be type A versus type B lactic acidosis. So, type A is the sort of shock, right? It's the inadequate oxygen delivery, aerobic glycolysis, shock, respiratory failure, cyanides, severe anemia, thromboembolisms, all can cause this because you're not getting as much oxygen to the cells. So, you're going to get a type A lactic acidosis. You can get this in exercise also, all right? Has anyone ever seen this in a marathoner or someone seizing that the lactate goes way, way up, right? Then, it comes right back down. All right. Then, what about type B? So, these are actually probably a lot more common than you realize. So, if the patient's lactate seems out of proportion to what they are doing clinically, you should always think about type B lactic acidosis. Ethanol, glycosine storage disease, not too common. Diabetes, yes. Malignancy, yes. But the big ones are drugs and thiamine deficiency, okay? The normal response to catecholamines like epinephrine is to generate lactate. If you are being scared by a lion and you're needing to run away on the plains of Africa 300,000 years ago, you may not have access to food for a little while. Our heart and our brains have evolved to function based on lactate. So, the surge in epinephrine causes our body to generate lactate and that serves as fuel for the Krebs cycle. Thiamine deficiency, if you don't have enough thiamine, you can't do aerobic glycolysis through the TCA cycle. The mitochondrial work, but you can't generate NADP to go into the Krebs cycle. I mean, into the mitochondria, okay? Krebs cycle arrests and then liver failure. These are other drugs that can cause type Bs, metformin, antiretrovirals, propofol, salicylates, and then various tumors. D-lactic acidosis are these sort of things where the bacteria are producing the lactate. This is pretty uncommon, okay? The symptoms are things like Kussmaul breathing, confusion, impaired alertness, gait disturbances, slurred speech. If you give a bunch of antimicrobials, if you've ingested a bunch of propylene glycol, if you have surgery or have other sorts of intestinal overgrowth problems, you can get into that. Okay. Let's turn into ketones. This is, I'm going to say, is probably the second biggest cause. So, we saw lactate is the most common. Ketones are your second most common. And there's many, many things that happen in the ICU that lead us to generate ketones. So, do we ever starve our patients, stress our patient? We generally don't give them alcohol. They generally sometimes have diabetes, and then they oftentimes are getting different drugs that could be contributing to this, including SGLT2 inhibitors and CRT on dextrose-free solutions, okay? How do we manage this? We need to give IV fluids, and then we need to give dextrose sources when the dextrose is low, and we need to give insulin, potassium, and phosphorus. Okay? And then bicarbonate is very controversial. Who gives bicarb in the setting of DKA? Raise your hands. Not very many people. What if I told you the patient's pH was 6.7? Would you give them bicarb then? Okay. All right. So, now the hand's changed. All right? So, it's controversial. We don't really know if it's beneficial or not, but it certainly makes a lot of us nervous if the pH is very low, but you really need to treat the underlying problem. All right. In the interest of time, I'm going to not spend too much time on this, but just to make it clear that these patients that come in with end-stage kidney disease that are DKA, they're generally not volume depleted, so you need to be very careful about giving them a whole ton of IV fluid. And then you also need to be careful about hemodialysis because it could very rapidly drop the serum osmolarity by removed glucose and everything else from there, and they can get some CNS edema from that. So, don't rush to put that ESRD patient who comes in in DKA with a pH of 6.7 on dialysis. You need to treat the underlying problem first. All right. Starvation ketosis. This is something we definitely all see. It develops over the course, usually, of a few weeks. And... I think that's about it for right there. Okay. Drug-induced ketoacidosis. So, we see this a lot. Epinephrine, I'm sorry, not epinephrine. Alcohol, SGLT inhibitors, aspirin, theophylline, acetone can all cause drug-induced ketoacidosis. SGLT inhibitors, who has seen this yet? Have you guys seen euglycemic DKA, right? Okay. This is due to inhibiting glucose reabsorption. You're peeing out a bunch of glucose, and so, because of that, you don't actually generate a very high glucose response. You need to stop the treatment. You need to give dextrose and insulin. Make sense? Okay. Now, this is one I just wanna call your attention to. Increasingly, we are using phosphorus-containing CRT solutions. The problem is is that they don't contain any dextrose, and so, as a result, you don't generally make your patients hypoglycemic, but you do often more tightly control the glucose. So, the amount of insulin they need goes way down, and so, the person who might've been on an insulin drip now might be just getting a little bit of insulin per day. If they are an insulin-dependent diabetic, their sugars are often too well-controlled for all the sliding-scale insulin protocols, and so, now, they're not getting insulin at which their body is dependent on, and they can go into a euglycemic DKA. So, again, you don't fix this by changing the solutions. You fix this by giving more dextrose, and then you can give insulin. Okay? All right. Aspirin. This is not a tox lecture, so I'll skip this. You can read through it if you want to. Okay, and then, in the interest of time, alcoholic ketoacidosis. So, when we drink a bunch of alcohol, we get decreased gluconeogenesis. We get an increase in NADH. We sort of shunt everything over. We don't necessarily have as much glucose intake, and we start depleting our glycogen stores, and then we start generating ketones. Okay? And then, we oftentimes have all these other counterregulatory hormones that also get upregulated and help generate ketones as well. The treatment for this is thiamine, glucose, volume repletion, insulin, and the such, if needed. These are the patients who you may not be thinking about this, but you give them some glucose when they come into the emergency department, and suddenly, they get super-acidemic because they got glucose before getting thiamine, potentially, and that's about it. Okay, I have to keep moving because there's so much on this topic. Toxic ingestions. We won't go into this too much because there's probably a tox lecture I can't tell, but again, if they have an osmolar gap, that's really important, and you need to think about, did they take something? But remember that patients who present late, like obtunded, may have a huge acid-base status, but they've already metabolized all their toxic alcohol, and so they may not necessarily have an osmolar gap. Okay, so it's a person who comes in, like obtunded, with a pH of 6.7, and you know, you check the lactate, and it's fine, and you check the beta-hydroxybutyrate, and it's fine. You sort of have to start thinking about other potential causes. Ethylene glycol, again, in the interest of time, I'll leave these for you to review offline because this is not necessarily a lecture focused on tox. I will say that of these two, methanol ingestion is way more problematic initially than ethylene glycol. Like ethylene glycol is gonna cause a lot of problems, but you're not gonna go blind or potentially die instantaneously. For methanol, you could. So methanol, you do need to recognize early on that it's a problem. All right, and you need to do dialysis. You need to think about competitive inhibitors like ethanol or, got too much on my brain. Yes, thank you, flamethasol. And then go from there. Okay, so non-gap acidosis, so hyperchloremic non-gap acidosis. So this is either a gain of acid or a loss of bicarbonate, really, for the most part. You're not gonna get asked these RTA questions on the boards. It would be very unfair to you. So hydrogen losses, we all know these, right? Like we can either be losing it in our urine, in our stool, or we could be hypokalemic or getting refeeding syndrome, causing some intracellular shifting. We can be generating too much bicarbonate. And then let me please correct something. Diuretics that we use in the hospital, they're not causing a contraction alkalosis, most of the time, okay? Unless you have objective evidence that your patient has been volume depleted to the point that they've been in the Sahara Desert, all right, they're causing a diuretic-induced metabolic alkalosis. They are upregulating the production of bicarbonate due to many factors when you give them to patients. So if the patient still looks fluid overloaded, you haven't caused a contraction alkalosis, you've caused a diuretic-induced alkalosis. And that's hard to fix. You oftentimes have to stop the diuretics for a little while. Okay, the pathophysiology. So the key here is that something generates the metabolic alkalosis, and then something is maintaining it. The body is very good at correcting metabolic alkalosis if you don't have something maintaining it. So if you stop those diuretics and you give the patient a little bit of time and the neurohormonal mechanisms that upregulated the bicarbonate production settle out, they will resolve that on their own pretty quickly. Volume depletion versus euvolemic, and then chloride-responsive versus chloride-resistant. These are the three sort of ways to think through these problems. So you wanna look at the volume status, and you wanna look at the chloride, and you may wanna look at the urine chloride to help you know if it's chloride-resistant or chloride-sensitive. If it's chloride-sensitive, giving them chloride will fix the problem. Okay, I think that is about it, because we are running out of time. Okay, respiratory acidosis. I don't need to tell a bunch of pulmonary experts about respiratory acidosis. The thing here to be mindful is is that we do cause a little bit of respiratory acidosis a lot, right? Because we do permissive hypercapnia. You can increase the minute ventilation if you really need to. Sometimes we may need to think about ECMO or ECOR if this is a really problem, like in a asthmatic or something like that, and then address the coexisting problems, because usually your body can tolerate respiratory acidosis. It's when you throw the metabolic acidosis on top of it that the pH is really gonna plummet, okay? And who's called nephrology and had nephrology say, well, I can't treat a respiratory acidosis with the dialysis machine? No one's ever had them say that to you? Okay, well, sometimes we're guilty of that. But it's what we're guilty of is really not really paying attention to the situation very closely, because a lot of times when we're consulting for this, the PCO2 may be high, and there could be a significant acute respiratory acidosis, but the real reason the pH is plummeting very quickly is because we're developing a superimposed organic acidosis on top of this, and a dialysis machine can certainly fix the superimposed organic acidosis problem. All right, so history and physical, resolution of the underlying cause, and then use temporizing measures is important, but secondary, okay? So you gotta do these first two, then maybe you can get bicarbonate. And if it's a code, don't get bicarbonate, right? Okay, all right, so I think I have a little bit of time there. Any questions on that? And then I'll do my last talk. That was a lot, okay? Do you guys feel pretty confident? I mean, most ICU doctors are pretty confident with acid-base disorders most of the time, okay? But think your way through it. If it's not 7.40, then ask yourself questions. Even in real life, it's good to ask the questions. If it's 7.36, why is it 7.36?

acid-base disorders

acidosis

anion gap

ketoacidosis

respiratory acidosis