REBOOT Hypoxemia Masterclass

Welcome to Critical Care Time, I'm one of your host Dr. Cyrus Askin and in just a little while, I'll be joined as always by my co-host Dr. Nick Mark. This coming episode is actually a reboot of our Hypoxemia Masterclass, and the reason being is that in just a couple weeks we'll be releasing our first of hopefully many episodes on mechanical ventilation. Nick and I figured this would be a great time to revisit Hypoxemia as we want to make sure that everyone's got a nice solid foundation before we tackle mechanical ventilation. So without further ado, buckle up and hopefully you'll enjoy this upcoming episode, this reboot of Hypoxemia. The delivery of oxygen is your cardiac output times your oxygen content of blood. And so when you think about how can you improve oxygen delivery, you can either improve the amount of hemoglobin, the saturation of hemoglobin, or you can increase the stroke volume or the heart rate. Those are kind of the parameters that you can adjust. And a lot of what we do in the ICU comes down to using medications or transfusions to adjust those things. Welcome to Critical Care Time, the podcast for everyone who cares for the critically ill. Nick and I are excited to bring this episode to you guys. It's going to be our first quote unquote solo episode for season two. Well, that being said without bearing the lead, any further Nick, why don't you tell our audience what we're going to be talking about today? All right, well, it's going to be an exciting one. We're going to talk about oxygen, specifically why it's so important, how it gets into you, and how that goes wrong. Specifically, we're going to do basically like a class on Hypoxemia and Hypoxia, talking about oxygen delivery utilization at the tissue level and everything oxygen related. That's awesome, Nick. That's exactly right. We're going to be doing a deep dive, a master class, if you will, exploring Hypoxemia and Hypoxia. For those of you that are critical care time veterans, we discussed this in part during our early season one episodes on shock. So for those that maybe new, if you haven't listened to those, go back and listen to those. They're early season early season one episodes that are definitely foundational topics. Assuming you've listened to those and you're ready to go, let's get started. Let's try to unravel and demystify Hypoxemia and Hypoxia. So just for some context here, oxygen is kind of the worst. It's toxic, it's corrosive, it's admirable. What do we talk about? You mean girls here? That's right. It's just terrible, right? Except of course, it is a fantastically good electronic sector and because of that, it is essential for all high energy life on earth. So 2.7 billion years ago, there was no oxygen on earth. And cyanobacteria started making it, it slowly accumulated. And because it's toxic, it basically killed like 99% of living things on earth. But the survivors started using it as a terminal electronic sector and it has basically enabled all of the complex amazing stuff that we do. And to be honest, essentially all of physiology and pathophysiology in the ICU boils down to the delivery and use of oxygen. If you're talking about exercise physiology, the ability to extract oxygen, we call VO2 max, is basically what differentiates average people from elite athletes. You know, that's what makes race sources amazing. In critical care, the failure to deliver oxygen, that's quintessentially what shock is, is the core physiologic arrangement we try to reverse. Whether it's a problem with getting oxygen into the body, whether it's a problem with having enough RBCs to carry oxygen or enough cardiac output to deliver that blood, we are constantly working in the ICU to optimize oxygen delivery. Nick incredibly well said. And I think given how important oxygen is for our biology, we thought that here on critical care time, we should do an episode devoted to oxygen, how it gets into the body, how we use it. And specifically, we want to put that ICU slant on it and discuss how we in the ICU can help deliver oxygen to our patients. And on a personal note, you know, Nick, I think we've talked about this before. Oxygen is kind of like our superhero origin story. For those of you that don't know, Nick and I met when we were recording a curbsiders episode on hypoxemia. And we were kind of nerding out on the physiology, on the teaching, this, that, got the chatting and realized, hey, we have this kind of shared interest in social media as it means to educate the next generation or the current generation of clinicians and other folks in the healthcare industry. And you know, one thing led to another and here we are. Yeah, so oxygen may be the worst, but it's how we became friends. So thank you, oxygen. We owe to you one. All right, let's get going, man. So, all right, so before we get too deep into the weeds, I think we should probably define some terms here for our listeners. Okay. And I talk about this with my residents, not infrequently. And I'm always surprised by how much confusion there is surrounding the terms hypoxemia and hypoxia. So with hypoxemia, really what we're talking about is a low oxygen tension in the blood. We're looking at that PIO2 in particular. And this is usually what we're measuring. We're trying to determine, you know, again, what is the oxygen content in the blood dissolved oxygen content in the blood specifically. Why do we care about that? Well, remember that while oxygen is principally about hemoglobin, it's not like there's a little receptor that just sucks oxygen off of hemoglobin, allowing it to get to end organs. In fact, oxygen needs to dissolve in the blood and then make its way eventually to the electron transport chain. And so that's why I really physiologically speaking or operationally speaking, we care about blood oxygen content specifically oxygen dissolved in the blood. You can contrast that with hypoxia, which is specifically an inadequate supply of oxygen at the tissue level, or inappropriate or inadequate utilization of oxygen at the tissue level, resulting eventually in end organ dysfunction and all of the hallmarks of shock. Right. So just to just to sort of summarize that great description. Hypoxemia is low oxygen in the blood. This is what we typically measure with a blood gas, or maybe indirectly with pulse-oxymetry. And then hypoxia is more of a qualitative concept, which is low oxygen at the level of the tissues. This is really what we care about even though this is often not something that we measure. To double click a little bit further on that, though, we should talk about the different kinds of hypoxia. And there's a couple. The most common is hypoxemic hypoxia. This is where you have low oxygen at the tissues because you have low oxygen in the blood. This is most of what we're going to talk about today. But there are a few other types that we need to talk about. There's ischemic hypoxia. This is where there's inadequate blood flow getting to the tissues. This could be a regional problem like you've got a blocked artery causing a stroke or an MI, or it could be a global problem. Like when you see in somebody in bad cardiogenic shock, they're just not pumping anywhere. Sometimes you'll also hear ischemic hypoxia called stagnant hypoxia, which kind of sums that up. Next, we've got anemic hypoxia. This is where the blood isn't carrying enough oxygen. This is usually something you see with acute blood loss or himalosis. It's usually not a chronic problem, but the idea here is the same. If the blood's not carrying oxygen, the tissues aren't getting it. You get anemic hypoxia. Finally, there's something called cytopathic hypoxia. This is where the tissues can't use the oxygen, which is delivered to them. You see this with certain toxins. You can also see it with a really bad mitochondrial dysfunction. Sometimes this is also called histotoxic hypoxia. Just to orient people, hypoxia and hypoxemia are not the same thing. They'll often go together. Within the larger bucket of hypoxia, there are several subtypes. We're going to talk about all of those more. Excellent. That's a great summary of the different types of hypoxemia. I think a little bit later in the show, we're going to discuss some examples where hypoxemia and hypoxia don't actually go together. That'll be an interesting little foray into some physiology. We've mentioned low oxygen in the blood several times, but I think we want to define that a little more rigorously. This is when we want to talk about the idea of oxygen content in the blood. Again, this is an equation I bring up every single time I come on to rounds in the ICU. That first day, introductory concept that I really want to hammer home with my residence is this idea of oxygen delivery. Oxygen delivery is really predicated upon two principal elements. The CAO2, which is the oxygen content in the blood. We're unpacked that a little bit as well as cardiac output. That kind of gets to your ischemic hypoxemia, for example, where if you have a depressed cardiac output, heart rate, time stroke volume being the equation for cardiac output, that can result in poor oxygen delivery. We'll take that element out of the equation. That's really the first compound term. The second one is this concept of CAO2, which is multiplied by cardiac output. CAO2 is equal to 1.34 times the hemoglobin times the saturation of hemoglobin plus 0.003 times the oxygen dissolved in the blood, which is that PAO2. Obviously, from there, you can tell that in most cases that PAO2 term is fairly minimal when it comes to oxygen delivery in comparison to oxygen that is bound to hemoglobin. Except in certain circumstances where, for example, the hemoglobin may be profoundly low. So in cases of significant anemia, especially in patients, for example, who may not be recipients of blood or blood products, that PAO2 term can actually become really, really important when it comes to delivering oxygen. And just as a quick caveat for our international listeners, those formulas are four millimeters of mercury of oxygen. If you are in Europe and you're using kilopascals, it's going to be a little different. So sorry about that. We just were Americans. We think think in America. Yeah. Pounds, dollars. very good. Drown, yeah, etc. Alright, so obviously, you know, I would be lying if I said that I calculate this every single time for every single patient. It's a little bit of a pain, so we don't really do that in practice. But what we do look at are our two principal terms. So that PAO2, which again is pretty easy to get off of an arterial blood gas, which is looking at that, the amount of oxygen that is dissolved in the blood. And we can look at the saturation or the peripheral saturation via a pulse oxymeter and get an idea as to what the SAO2. So the SPO2 and the SAO2 are somewhat analogous. One is a peripheral set that's obtained non-advasively and one is obtained from an arterial blood gas, run through a blood gas analyzer. Right. And so the core concept there is you need to think about how much oxygen the blood can carry. Most of that oxygen is bound to hemoglobin, but a little tiny bit is also dissolved. Excellent. And Nick, I know you're a big fan of comparative physiology and will physiology. Any interesting tidbits you wanted to share here? Why yes indeed. So sometimes it's the exceptions that help define the rule, right? And for every single vertebrate on Earth, this formula applies except one. There's one species that does not follow the rules. It's a species called the Arctic ice fish. It doesn't have red one cells, it doesn't have hemoglobin. It carries all of its oxygen dissolved in plasma. And in order to do this, it has to do a couple of interesting tricks. And they're kind of, they tell us something about our physiology too. So first off, the Arctic ice fish has a really big heart for a fish. It's about three or five times larger than other comparably sized fish. So it has a large cardiac output. Second, it lives in the Arctic. It's cold. And in cold, you can dissolve more oxygen. So you can have about three times more oxygen in the blood. Third, it has these gigantic capillaries. And that means that it has a really low SVR. So it's low resistance for that heart to pump against. And then finally, it's last sort of trick is it doesn't use a lot of oxygen. It has a very low VO2 because it's just this little kind of lazy fish. But anyway, if you think about that, the strategies that it uses, right? Having a high cardiac output, dissolving as much oxygen as possible, having a low SVR to pump against, and then keeping the VO2 max low or VO2 max, VO2 low is a very effective combination of waste, improve oxygen delivery. So this Arctic fish can teach us a lot. It's fascinating, Nick, because I think just as a quick aside, a lot of the things we do in our kind of the sickest of the sick patients kind of mirror what this Arctic fish is doing on a regular basis. So huge heart, okay, we can't really make your heart bigger, but we can use mechanical circulatory support to help you out. You know, things. And there's case reports, by the way, of people where they couldn't get a matched transfusion. So what did they do? They did things like they hyper-oxygenated them, they cooled them so their oxygen consumption would go down. And then they used ionotropes to improve oxygen delivery, and maybe I know dilators to lower SVR to improve it even more. So basically what you could do in a situation where somebody is super anemic and they have anemic hypoxia, they're not carrying enough oxygen, is you can. You can basically do all the adaptations the Arctic ice fish has. Low body temp, high dissolved oxygen, make your cardiac output super-physiologically high in your SVR low. Pretty cool. Yeah, pretty cool. Prudetion, paralysis, cooling. I've had cases before where we actually teamed up with hyperbarics to try to increase that PAO2. So another option. Right. Absolutely. Yeah, even though it's.003, if you play your cards right, you can make it like maybe.1. Which is what the Arctic ice does. So he's spent a good while now talking about oxygen delivery and sort of alluding to the fact that oxygen is critical. But this is an opportunity for us to throw back to our biology classes in ninth grade. And remember that oxygen is really the linchpin when it comes to the efficient production of ATP, which is really the currency upon which our cells trade on. So it was kind of popularized in the song from the late 1990s. It's all about the ATP baby, right? So problems can typically arise in patients when there is not enough oxygen to produce ATP. And so again, recall Nick, as you said, that it's kind of the final electron receptor in the electron transport chain, allowing that ATP synthetase to do its job and produce all that ATP in the absence of ATP, we're relying, excuse me, in the absence of oxygen, we're really relying more and more on anaerobic respiration, Krebs cycle, et cetera, which is just not as effective at producing ATP per unit time. And so if you take a step back and you look at oxygen delivery, we're suction consumption, and so what we see our oxygen delivery is occurring in a ratio of about four to one when it comes to how much oxygen is delivered per unit time versus being used. And it's easy to remember this when you think about saturation. So typical saturation in arterial blood, typical oxygen saturation arterial blood is in the neighborhood of 98, 96 to 100 percent, something like that. Okay. Then if you look at blood in the central venous circulation, and then again in the mixed venous circulation, so from a PA catheter, you're really getting close to 75, 70, maybe a little bit lower than that, but somewhere in the neighborhood is 70 or so percent. So the way I conceptualize that is every hemoglobin molecule has four hemoyities, each of which is bound to oxygen, typically if you have 100 percent oxygen saturation. And so as a red blood cell, if it's gobs and gobs of hemoglobin is making its way around the body, on aggregate only one oxygen molecule is going to dissociate from those four hememoyities, resulting in an ending saturation of about 75 percent, we call it, you know, 75 percent, whatever. So another way of looking at this is basically only a quarter of oxygen is really extracted under normal circumstances as a red blood cell is sort of making its way from left heart to right heart. Exactly, and that's a great way to remember that under normal conditions your DO2 is about four times your VO2, you might be using about 250 ml of oxygen, but you're actually pumping about a liter of oxygen around your body. Important to remember that it gets harder to take those oxygen molecules off, right? Remember there's cooperativity on hemoglobin, so like going from 100 down to 75 percent is easy, that's one going off, but knocking off a second, third or even fourth oxygen is much harder. And so yes, you have this big reserve, but you really can't use all of it, right? It's kind of like, you know, that bottom of the fuel tank where it just doesn't go to the engine, you need to keep it full. You really can't extract 100 percent. And as you start to extract more than about 25 percent, and certainly as you start to extract more than 50 percent, then some parts of the body are going to start not getting enough. And that's when you start to see this shift towards lactate. That's excellent. Yeah. And this is another really important point I think for our listeners and for early learners is it's not a switch, right? It's not like you go from anaerobic to anaerobic respiration like that. There's sort of a transition, a spectrum of metabolism that's occurring. And as that oxygen utilization is increasing and as your saturation is maybe dropping, you're starting to see a rise in lactate production, something that you can see demonstrated on cardiopulmonary exercise tests in the PFT lab, things like that. So definitely an important physiologic point to I think drive home. Now we've talked about anaerobic respiration a little bit here and we know that it's used principally in certain organisms. So why don't we just do that? Why don't we just do anaerobic respiration and forget this oxygen molecule? Yeah. So I mean, we do. It's just not very efficient. Now I promise I won't use any horrible flashbacky phrases like Gibbs free energy, but just remember that with anaerobic metabolism, one molecule of glucose is going to produce two ATP as opposed to like 38 with aerobic metabolism. So you could think about it as using oxygen makes your metabolism 16 times more efficient. And I think if human beings is like high-performance sports cars, we need that high-octane fuel. We're not happy running on regular low-octane fuel. We have these big brains and hearts which are optimized for things like writing poetry and running marathons and they just can't work optimally on an energy source that's 16 times less efficient. There are tissues in our body like muscles that can make the switch to lactate very efficiently, but not all of our body can. And when we start to switch over to lactate, we have this, we have, to anaerobic metabolism, we need something else to be the terminal electron receptor. And as a result, we end up producing lactate acid. And that comes with costs, right? Because it also causes acidosis. And so, you know, now some of our tissues like muscles can and do go anaerobic, but when they do, they need to use a different terminal electron receptor to replace oxygen. And in humans, that means producing lactate acid. Hmm. You put an interesting emphasis on humans, Nick. Is there another animal you wanted to bring up here? Yes. So, here's kind of a fun fact one, not quite as physiologically useful. But so instead of producing lactate, goldfish actually produce ethanol under aerobic conditions, which they excrete through their gills. So if you were to like make a goldfish anaerobic, it would slowly start making its tank alcoholic. Hmm. I'm very intrigued here. So I wonder if the goldfish couldn't excrete the alcohol through their gills. Would they just be drunk all the time and bouncing into the walls? Exactly. So they're like high on their own supply. I could also imagine some like incredibly overpriced liquor that that's derived from goldfish. - I love to call Elon up on that one. - Yep, it sounds like. - All right, so now that we've discussed goldfish and their ability to generate ethanol, definitely a highly germane topic as it relates to our friends in the intensive care unit. Let's take some time to unpack the VO2 concept as it relates to DO2. So you spend a lot of time talking about DO2, but not so much VO2. So VO2 again is really that oxygen consumption piece. And so not only do you have to take into account what you're delivering, but you also have to take into account what you're using. It has to be that balance there that we've discussed that four to one ratio. So many of the ways in which we determine, quote unquote, VO2 are really estimates. So even things like the FIC method, thermo dilution, there's equations that are available online that take into account size, but not necessary body composition. A lot of those techniques used to look at cardiac output, VO2, they're predicated upon some degree of estimation based on the patient size or other demographic factors. Really, if you're trying to determine VO2 more in a more kind of patient centered or more specific manner, then you're talking about cardio pulmonary exercise testing in the PFT lab or a metabolic cart in the ICU. And we talked a little bit about metabolic carts with Dr. Wishmeyer, when we were talking about nutrition in the ICU, using them to determine if you're overfeeding or underfeeding a patient. But really, those are really great tools to determine VO2. And then you can calculate VO2 and look at those two terms in comparison. Absolutely. I think that, you know, just you got to remember that your VO2 is your cardiac output times your oxygen content. And so that means that there's a couple of interventions that you can do to improve delivery. First, you can improve cardiac output, either increasing the heart rate or the stroke volume or maybe by decreasing afterload, you can increase the stroke volume indirectly. And then in terms of oxygen content, well, you can either improve the saturation or you can improve the amount of hemoglobin. And, you know, lots of studies of yesterday year thought that superphysiologic concentrations of hemoglobin would improve oxygen delivery. And most of those failed, right? It's kind of a threshold thing. You either have enough hemoglobin to deliver oxygen or you don't. Is rare cases where more hemoglobin is a good thing. Excellent. So now that we've really discussed the relationship between VO2 and VO2 in a very purposeful way, I did Nick want to take an opportunity to unpack to an even greater extent the different types of hypoxia that we can see in our patients, starting with this idea of hypoxemic hypoxia. So again, probably the most common type of hypoxia we see. And this is really when you have a true oxygen deficiency. And probably is why people will erroneously confuse hypoxia and hypoxemia because these two do often, but not always go hand in hand. So basically in hypoxemic hypoxia, you have low oxygen in the blood, which is causing low oxygen at the tissue level. And usually this is a problem with really getting ambient oxygen or enriched oxygen through the lungs and into the blood eventually to end organs. And really we're going to break that down even further. In the latter half of this episode, we're going to talk about the six, not five, but six major causes for hypoxemic hypoxia. Absolutely. Before we double click on all the things that can cause hypoxemic hypoxia, we should talk about the other hypoxias. So remember, there's a schematic, anemic, and cytotoxic, or kind of the other boxes. A schematic hypoxia is where the issue is impaired blood flow, stasis of blood, blood not getting to the tissues that need oxygen. This can be, as I said before, this can be a regional phenomenon. You have a stroke or an MI because an artery is blocked. Or it could be a global problem. Somebody is in cardiogen shock and they're not pumping. It could also be a transient phenomenon. So when MMA fighters get choked unconscious, or when pilots lose consciousness in a hygiene maneuver, so-called G-lock, the issue there is exactly the same. It's because blood isn't getting to the brain. Absolutely. It's all about oxygen delivery. We can make anything about oxygen delivery if we try. Awesome, Nick. So we've talked about a schematic hypoxia. Do you want to walk us through the other types of hypoxia that our listeners need to be familiar with? Absolutely. So anemic hypoxia, which is impaired oxygen delivery because of low oxygen content. This is usually due to acute blood loss. Occasionally, you can see this with people who have really severe anemia, or amolosis, et cetera. And usually what's going on here is that the saturation and the dissolved oxygen are normal, but the oxygen content is really low. So if you use that formula and you take into account the low hemoglobin, you'll see that they're actually carrying a ridiculously low amount of this. Now, this is confusing for people, because people are like, wait, if your tissues are hypoxic, why aren't your sat's low? And the answer is, is your sat's could be fine, just not enough oxygen in arterial blood. Now, we could talk about this more later. Theoretically, it is possible to develop hypoxemia, low oxygen levels in the blood because of anemia. Like if you drop your sat's so low that the blood returning to the heart has a super low sat, it may not be able to come all the way up. Let's put a pin in that. And we can talk about that when we talk about the sixth cause of hypoxemic hypoxia. Excellent. Excellent. And I think there is one more cause of hypoxia that we wanted to talk about, this idea of cytotoxic hypoxia. Yeah, so this is like a really classic sort of board exam question, which is like somebody gets brought in after a warehouse fire. They're extricated. And suddenly, you examine them. And their lactate is like 17, but their PAO2 is normal, and their sat's are normal. Why? Well, the answer is usually cyanide. Many household items like silk, wool, polyurethane, plastics, nylon, when they burn, especially at high temperatures, they liberate cyanide. And people breathe in cyanide, and it gets out into their tissues, it binds to complex four and the electric transport chain and stops it from using oxygen. So this is kind of like the water, water everywhere, nor any drop to drink situation where like your tissues can't use the oxygen. So your saturation and your oxygen content are going to be normal or even super, super normal. But your tissues are still behaving as if they're they're anaerobic. And so you see lactate production and all that. So this is fortunately not a very common occurrence, but it's a very important thing to recognize on exams and rarely when you may see it in practice. The hallmark here is a high oxygen content and a rise in mixed-venous oxygen. That's true. All right, Nick. So I think that was a great review of the causes of hypoxia that we need to be familiar with. Now, in the latter half of this episode, what we're really going to focus on is that hypoxemic hypoxia and specifically the six primary causes for hypoxemia. These are going to be pretty commonly seen in the ICU, sometimes in the outpatient environment. So we really want our listeners to be familiar with these six primary causes. And so we're going to take some time here to go through them now. All right, so on critical care time, you guys know we like to approach things via a case-based model. And we're going to use that same model as we explore hypoxemia, specifically hypoxic hypoxemia. So we'll start with a case, as I kind of alluded to. Nick, let's say that you're climbing Mount Rainier. And you see John across the way looking very unhappy. He's short at breath, he's cyanotic. Looks like he might have ascended to rapidly from sea level to an altitude of 14,000 feet over a single day. Initially, he was doing OK. After several hours at high altitude, though, he began experiencing some shortness of breath, fatigue, mild headache, things worsened overnight. And ultimately, he's seeking medical help. So Nick, what do we think is going on? And might there be some hypoxemia at play here? So sure sounds like it. We should do an episode sometime about altitude illness. There's a lot of fun stuff we can unpack with altitude sickness, hay, pace, et cetera, just to keep this focused on oxygen. So it sounds like what's going on with John is that he's got hypoxemia due to low inspired oxygen, which is an issue at high altitude. At sea level, the atmospheric pressure is about 760 millimeters per mercury-- sorry, Europeans, US units again-- 21% of that ambient air is oxygen. So there's a partial pressure of oxygen, which is about 160 millimeters per mercury. It's a little bit less. By the time it gets into our lungs, we'll talk about that in a second, because there's a lot of water vapor in your lungs. But as we ascend, atmospheric pressure is going to drop pretty rapidly. So at 14,000 feet, the atmospheric pressure is about 450 millimeters of mercury. It's about 60% what it is at sea level. And that means that he's only getting about 70 millimeters of mercury of oxygen, which is half what he would be getting at sea level. And that's probably not enough for some people. And he probably feels lousy as a result of that. Great discussion. So this is maybe a good time to introduce the idea of the ABG and how it relates to patients like this and some of the other patients we're going to talk about. So I'll introduce the concept by saying these folks should have what's called a normal AA difference, or most commonly, I think, refer to as an AA gradient. Okay, cool. What does that mean, Nick? Yeah, so you can think about your AA, gradient, or AA difference as the difference in oxygen concentration between alveoli and the arteries. The reason why I call it a difference in not a gradient, one of the people taught me physiology taught it to me this way, that's number one. But number two, just conceptually it makes sense. It's not really a gradient, right? It's like if I go from one room to another, there's not a gradient, either in one room or the other. It's the oxygen contents in the alveoli or in the arteries and the difference between those. So I don't know. You want to be fancy, call it a gradient, that's fine. But I'm going to call it a difference on this show. Now, let's talk about why we care about it. And basically, we could think about it as a way to measure how effectively oxygen is getting from alveoli into the arteries, right? So it kind of tells us how the lungs are working. And the idea here is that by comparing these two, we're using a difference between them, we could see how effectively oxygen is getting from alveoli into the blood. I should say that it's kind of hard to like stick a catheter into somebody's alveoli. So we don't actually measure that. We use an equation called the alveolar gas equation to estimate what the contents of the alveoli are. And for the sake of brevity, let's not talk about where that comes from. It's on the one-pager, it's on MD-Calc. The key concept here is that the AA difference tells us how efficiently oxygen is moving from the alveoli into the blood. And an AA difference is either normal or increased. And if it's increased, it means the lungs aren't exchanging oxygen and carbon dioxide very well. A normal AA difference means the lungs are working fine. And so in this case, right, Johns lungs are probably fine, at least assuming he doesn't have pulmonary edema for an altitude. And so I would expect that this normal AA difference kind of tells us that the issue is not Johns lungs, it's the low oxygen tension in the ambient air. That's right. Yeah, so it really makes pretty good sense. So the lungs are working fine, assuming there's no pulmonary edema or anything else going on. The issue is just that there is not enough oxygen in the atmosphere where that patient is. And importantly, if we give Johns supplemental oxygen, I would expect his hypoxemia to completely resolve. If the issue is low-inspired oxygen and we let him inspire more oxygen, we pretty much fix that problem. Now I will sort of double click on one nomenclature thing here that people sometimes get wrong. First of all, for whatever reason, low-inspired oxygen is always the first thing that we talk about. And it's by far the rarest cause of hypoxemia, right? Unless you happen to be on top of an out-rated air or whatever. I mean, one of my colleagues, one of my partners climbed out right near like yesterday. So I mean, it does happen. But most hypoxia that we see in the hospital is not that. Sometimes people will confuse FIO2 with inspired oxygen. And so FIO2 is the fraction of oxygen. Technically, John is breathing the same fraction of oxygen as you and I are at sea level. The fraction of oxygen is 21% at sea level, is 21% at 14,000 feet. It's 21,000. It's 21% at the summit of Mount Everest. The difference is the barometric pressure, right? That's what's actually dropping. I should say though, there are a couple situations that you will encounter or could encounter at sea level where somebody might have low-inspired oxygen. Occasionally, they'll be like big steel structures, like not accessed parts of ships, where rust forms and it depletes the atmosphere of oxygen. So it's a low oxygen environment. Another situation you see sometimes is another gas is displacing oxygen. So people working with dry ice or liquid nitrogen, CO2 and nitrogen can displace oxygen. And then finally, I've actually seen this before, if you have like a fire suppression system in like a data center, right? It fires all this gas to push all the oxygen out and stop fires. And anyone who happens to be in there is going to not enjoy that because they're going to be hypoxic. Oh, yeah. It's just like in Terminator 2. Yes, precisely. Oh, man. Okay, so let's go on to the next case. So, sorry, so you are called to the bedside to assess Janus, a 64-year-old with a history of obesity and obstructive sleep apnea, who is not adherent to her CPAP, who is in the pack you. She had a minor procedure under anesthesia and she was extubated. The bedside nurse notes that she's got low oxygen saturation and a draw blood gas, which shows both hypoxemia and hypercarbia. The nurse notes that the case was shorter than expected and the patient got a bull is a fentanyl right around the end of the case, right before the pack you. Patient met criteria for extubation, but they were kind of sominal and afterwards. As I said, we get an ABG, it shows low PO2 and high PCO2. Awesome. So what are you thinking? What's going on here? This is not really a big head scratch, or I will say. We kind of gave this is like the Denny's Grand Slam breakfast of hyperventilation, right? So it's like all the elements of a nutritious and delicious breakfast. So really, again, this is a case of hyperventilation. This patient is set up for hyperventilation for a number of reasons, right? Okay, so she's got pre-existing anatomy that probably results in some degree of impaired chest wall excursion. Perhaps even one awake, but certainly when asleep and soft tissues are more relaxed and you're kind of supine, that can cause just some mechanical hyperventilation. We then add to that the fact that this patient has gotten sedatives, has gotten opiates which typically reduce your, inherent drive to breathe. And so you've got both kind of physiologic and anatomic reasons for hyperventilation. I think that's almost certainly what's going on here, Nick. Absolutely. And so if we were to calculate her AA difference, it would be normal in this case as well. Because the issue is not, it's not a problem with her lungs getting oxygen into her blood. The issue is getting oxygen into her lungs in the first place, right? In that first case, it was because there wasn't enough oxygen in the environment. In this case, it's because maybe she's got, you know, a tissue in her mouth, which is just an end, you know, her brain is not sending a signal to breathe. So the oxygen is not getting down into the lungs. She's got alveolar hypodermin. That's right, Nick. So we give a supplemental oxygen that should improve that AA difference. It should improve the hypoxemia. But the problem is that's not really going to fix everything here. So we're not really talking about hypercapnea necessarily on this episode or sort of pure type two respiratory failure. But in this case, we said this patient has hypercapnea. And so really, what you're going to need to do there is not just treat their hypoxemia, but you're going to need to improve their ventilation as well. So this is someone who probably would benefit from enriched air. So, you know, this is probably someone who would write, this is probably someone who would benefit from air enriched with oxygen. So, you know, whatever FIO2, you want to crank their, their oxygen source up to, but also someone who would benefit from maybe some non-invasive. If they're a good candidate for that to try to help with the ventilation component too. Absolutely. So CPAP with some blow by oxygen. You know, remember, you know, here the hallmark of alveolar hypodermalation is that they have a normal AA difference. It will respond to supplemental oxygen. And that in addition to seeing hypoxemia, low PIO2, you'll also see a high PCO to a high carbon dioxide. All right. On to the next case. So you are caring for a patient on the medicine wards with a diagnosis of pancreatic adenocarcinoma. The patient was admitted for management of acute renal failure. You get called to the bedside because he's suddenly got acute onset to kipnia, tachycardia, and hypoxemia. He's breathing like 30 times a minute. His blood gas shows a normal pH and PCO2, but a very low PIO2. You go through the history with the nurse and you find out that he's been bedridden for like five days. He's always been in the hospital. He has been declining his heparin shots. You get a chest x rag. It shows nothing. You get a CT pulmonary angiogram, which shows big, inclusive thrombi and multiple branches bilaterally. You throw on some nasal cannula and his oxygenation comes back up to normal from like 85% up to like, you know, 94%. So what's going on here? Yeah. So this is a pretty classic case of hypoxemia due to VQ or ventilation perfusion mismatch. So the patient is probably ventilating effectively. In other words, their airways, their LVLi, they're doing what they're supposed to be doing, but the significant clot burden is what's impairing blood flow. So functionally, you're reducing VQ in VQ. And so VQ mismatch, generally, if it's a pure VQ mismatch, should correct with supplemental oxygen. That's partially why it's so important to check a room air sat for people that have PE. And then when you give them supplemental oxygen, you can kind of do a post check. Right. Whenever I see somebody with a PE who's on like two liters of oxygen, their sat's are 99. My first question is like, well, what were their sat's on ambient air? Because often you can see the degree of VQ mismatch by the degree of hypoxemia on ambient air. So let's double click on the physiology a little bit here. So, you've got 300 million LVLi in your lung. And some of them are better than others. They're not all quite the same. So some of them have technical term like schmutz. Yes, that could be mucus, that could be water, that could be protein, that could be blood, could be pneumonia, it could be a lot of things. But there are some LVLi that have stuff in them that don't do a good job or for as good a job exchanging oxygen. Fortunately, your lungs are pretty smart. And because of a process called hypoxic pulmonary vasoconstriction, the blood vessels going to poorly ventilated parts along will constrict. And then blood will, therefore, go to the better ventilated parts. So it's kind of redirecting blood flow in this smart way, where it goes to the most efficient units-- - Away from the schmutz. - Away from the schmutz, exactly. The problem is, is that when you have a bunch of big thrombi, they're blocking the urupalmonary arteries, now because of the pressure, blood redistributes kind of to the rest of the lung. And instead of having careful VQ matching, which is optimizing, now the blood's basically just kind of going wherever it can go. And what that means is that when blood flow gets redistributed to schmutz-filled alveoli, you're going to see less good VQ matching. You've got more Q going to badly ventilated areas. And that's the mechanism of hypoxemia in pulmonary embolism. - So getting back to this concept of the AA difference or AA gradient, really, it should be increased. There's going to be a disconnect between the oxygen content within the alveoli and what's actually making it into the blood, because there's either schmutz as you so eloquently put it, nick, in the alveoli, or there's a flow limitation of some sort. So we can also see VQ mismatch in other disease states. So a good example of this would be obstructive lung diseases specifically in acute exacerbations of COPD. So these acute exacerbations can result in kind of an increase in airway inflammation, which in the setting of already compromised lung tissue can lead to reduced ventilation relative to perfusion. So this is kind of the reverse of the VQ mismatch we talked about before, where it was a blood flow issue. Now it's really a ventilation issue. Now, Nick, as you kind of alluded to, that inborn hypoxic pulmonary basal constriction that does occur tends to mitigate against some of this. And we've discussed this in the past with our COPD patients. One of the big problems is you over oxygenate them, and you sort of flip the switch on this adaptive mechanism resulting in downstream problems. Exactly. And we'll double click on that a little bit more in the next case, I think. But I think I put a put a pin in that. Remember hypoxic pulmonary basal constriction super important. That's what normally maintains effective VQ matching. But sometimes when you have things that perturb VQ matching, you can get hypoxic. I think we should talk about one sort of related issue here, which is the concept of dead space. So people often think that dead space causes hypoxemia. It does not. What's going on with dead space is, like, let's say that I've got a big clot, blocking off blood flow to half my lungs. Well, obviously that half my lungs is not going to get any oxygen in. But importantly, it's also not going to get any CO2 out. And what that means is that if I have a normal minute ventilation of five liters, but now suddenly half of my lung has become dead space, now I'm going to have to breathe twice as much in order to get rid of the same amount of CO2. And this is the key concept here. Remember in the case we said that this person was hyperventilating, but they had a normal CO2. That is a huge red flag. And that is something that people need to learn to watch for it and learn what it means. What it's telling you is that either they are producing a ton of CO2, and this guy has to breathe 30 times a minute to blow off all that CO2, or that his lungs aren't working very well. And maybe he's got a huge amount of dead space. So he's only able, you know, he needs to breathe twice as much, because half of his lung isn't participating in gas exchange. Either way, very important to remember that increased dead space is a big red flag, and it causes hypercarbia, not hypoxemia. On that note, Nick, let's move on to another case. So here we have a 34-year-old with a diagnosis, a new diagnosis of pulmonary arteriohypertension. She's admitted for management of pylonifritus refractory to oral antibiotics. She develops hypotension, signs of shock. She's transferred to the ICU. Blood cultures are all positive in four samples for gram-negative rods. And the patient develops some hypoxemia during the first night in the ICU. You get a chest x-ray that's unrevealing, but interestingly enough, when you're trying to treat her, you're putting some supplemental oxygen on board, and she does not correct, okay? So you're giver oxygen, and that sat does not improve. You get an ABG, the ABG reveals hypoxemia without hypercarbia, and you calculate that she's got this increased AA difference. You then astutely call for a stat echocardiogram with a bubble study, and she's noted to have bubble scene in the LV within one cardiac cycle. So within one beat, you've got bubble scene in the LV. Nick, can you break down what's going on? Yeah, this is a classic story for shunt. There's a couple of features to call out here. So first of all, hypoxemia that does not correct with supplemental oxygen, that is the hallmark of shunt physiology. Essentially, what's going on here is it doesn't matter how much I can improve oxygenation because deoxygenated blood is mixing with it. Now, shunts can happen different ways. You can have shunt inside the lungs, or you can have shunt outside the lungs. In this case, it sounds like we're talking about an intracardiach shunt. The bubble study shows us that we agitate some saline. We inject it into the right heart, but immediately we can see it in the left heart. So bubbles must be crossing over quickly. If it was an intraculmonary shunt, it would take a few more beats to get over there. So common things being common, we all have H-roseceptal defects when we're in utero. For most of us, three quarters, it closes, but some people still have it. And in some cases, when people have really high right-sided pressures, it can cause an ASD to open and you can get a right-to-left shunt causing hypoxia. This is a common situation. There are other types of shunt that you could think about as well, but I think that's probably the one to point to here. Perfect. And as you sort of alluded to in that discussion of how many beats is it take for the bubbles to appear on the left side of the heart? So there are intraculmonary shunts as well. So an example would be pulmonary AVMs. Those could be seen on pulmonary angiography. And then there's also this physiologic shunting too. And we sort of alluded to that in our previous discussion. But you can see that in adelectasis, pneumonia and ARDS, often in concert with VQ mismatch. You'll note that for example in these folks, you give them supplemental oxygen, they have a partial improvement, but not a total improvement because that VQ mismatch and that should be causing hypoxic vasoconstriction, let's say, it's not working totally perfectly. So you still have some really, for lack of a better term, shunting a blood to regions of lung tissue that are not effectively participating in gas exchange. Exactly. And I think shunt is a really crucial concept for our listeners to understand. And this is something that I probably see misunderstood once a week. And I'll tell you how this typically presents. So this is typically, there's somebody in the emergency room who's volume overloaded heart failure that got big plural of fusions. And they're in a fib. And somebody decides to put them on deltihism, troll their rate or whatever. And suddenly they get hypoxic. Their sats are stuck at 88%. They get put on supplemental oxygen. And their sats don't come up all the way. They come up maybe like to 92%. So what happened here? Well, what happened here was you had some poorly ventilated schmutz-filled alkyl. Back in the schmutz. Yes. Maybe you got like a big plural of fusion. You got some adalactasis. You have a whole bottom of one lung is collapsed and floating in this big effusion. And the lungs were smart. They were not sending any blood flow to that area. There was effective hypoxic pulmonary basal constriction. But then you did something not so smart, which is you gave them a medication which inhibited hypoxic pulmonary basal constriction. Examples of meds like this are like nitrates, calcium channel blockers. And what then happened was now they started to send blood through that collapsed lung or through that schmutz-filled part of the lung. And now they get hypoxic. And so the answer for this person is stop the deltihism. Once it's gone from their system, their sats will return to normal. And I would say this is something that I probably see once a week in practice, even though it often goes unrecognized because if you don't understand the physiology. Nick, I'm really glad we took some time to discuss that. I think it's a really important element of this discussion of shunt physiology. It's something that I really didn't learn until late in my training. So I'm glad we were able to spend some time on it today. Do you want to sort of then take a step back and summarize what we've discussed as it relates to shunt? Absolutely. So think about shunt when somebody is hypoxic. And it does not correct fully with supplemental oxygen. Also remember that it will have an increased AA difference. Beautiful. Beautiful, Nick. OK. Let's perhaps move on then to the fifth of our six causes of hypoxemic hypoxia. Do you have another case? I'll give this one to you. Yeah. So Ralph is a 58-year-old retired construction worker coming to the ED with shortness of breath. He's got an extensive smoking history. He's diagnosed with COPD. He's never had PFTs. He's on teotropium corticosteroids. In the ED, his sats are 93% on air. But when he walks, even just like moving around in bed or going to the bathroom, his sats fall precipitously to 84%. When he's put on just three liters of supplemental oxygen to go for imaging, his sats come up to normal. And if he's on supplement oxygen and he walks, he doesn't desat. Beautiful. OK. All right. Do you have any imaging on this gentleman? Um. Let's, yeah, sure. So he's got a UIP pattern on his seat. - Okay, great. Hold him that one from me. Okay. So. - Velcro like crackles. - Okay, perfect. All right, so this is a patient who, really even without the imaging is sort of set up for having maybe diffusion limitation as being the cause for their hypoxemia. So why is that the case? The sort of classic patient is someone who perhaps that rest has a low normal oxygen saturation or even a frankly normal saturation, but then when they start to move and exert themselves, even with sometimes minimal exertion, you see a drop in their oxygen saturation. Typically that's going to be associated with some physical exam findings, perhaps on oscillation of the lungs, and then imaging that will suggest there could be some perturbation to the alveolar capillary interface. And so what's probably going on in this case is this person with their UIP pattern, which may very well be, which may very well be idiopathic pulmonary fibrosis or IPF, that dysregulated fibroblast activity is resulting in essentially scar tissue being laid down in between where the alveoli and capillary beds should be interfacing nice and smoothly. And so that increased distance between blood vessel and alveoli is actually impairing or limiting diffusion of oxygen in that particular scenario, which at rest isn't such a big deal. But when you compound that with an increase in cardiac output, like if that person is exerting themselves, not only have you now subjected them or not only do they have an increased distance that oxygen is going to need to travel to get from alveoli to capillary bed, but also blood flow is going to be moving faster per unit time. So the contact time, if you will, is going to be reduced. And so that's really kind of the physiology I think that's going on in a case like this. - Right, exactly. So remember that diffusion is going to depend on the thickness of what it's diffusing through. That's, I guess that's fixed other law. We don't, we're not as excited about that one, I guess. But so when you have something like fibrosis and that exceptionally thin interface between capillary and alveoli is thickened, now diffusion is going to be impaired. But there's a really important thing to understand here, which is that it doesn't matter most of the time when you're at rest. And the reason is is that there's this incredible amount of excess capacity in the lungs. So imagine you're a red blood cell and you're squeezing through the pulmonary capillaries going in between two alveoli. It takes you at rest about a second to go through the pulmonary capillaries. And within the first third of a second, you're fully oxygenated. And what that means is that even if the interstitian is thickened, even if it's twice as thick as normally, even if a diffusion is substantially impaired, you still have enough time if you're moving at that slow rate to load up on oxygen. It will just take longer. So instead of it taking a third of a second, maybe it'll take half a second. But during exercise, when your cardiac output increases, your blood flow increases, and the transit time of RBCs through the pulmonary capillaries goes down. And now what happens is those RBCs that are going past thickened interstitian, they don't have enough time to fully oxygenate. And that's why with diffusion limitation, you'll often see normalish sats at rest, but desaturation with exertion. That's kind of the hallmark physiologic feature. - Excellent, Nick. So I think to summarize, really, you're gonna have an AA difference that's increased, kind of makes sense. The PAO2 will typically improve with supplemental oxygen, and at least in kind of early stages of this disease process, that impaired diffusion is really, that impaired diffusion may only be clinically apparent during times of exertion. What I will say is your classic kind of IPF patient is always on oxygen towards the, you know, latter half of their disease process, because even things like just kind of ADLs and IADLs, you know, basic activities are enough to bring out that hypoxemia. And we should also say that, you know, you can have more than one of these processes at once, you know, it's possible to have more than one of these coexisting, right? Many people who have diffusion and limitation will also have some degree of EQ mismatch. So it's not purely one or the other, but really what we're saying is like, what's the primary process here? - Excellent, awesome. - So this brings us to the final and most often overlooked cause of hypoxemia. When most people teach this, they say that there are five causes, but there's really six, and the sixth cause of hypoxemia, in my opinion, kind of ties it all together, it kind of ties the room together. It makes the physiology of oxygen delivery in a sense. So you have a case for me here. - Yeah, and it's probably my favorite one to teach on too, 'cause it is kind of a nice unifying concept. So here we've got a 22 year old lady who's got a history of alupus. It's complicated by alupus nephritis, anemia of chronic kidney disease, and then she also has anemia chronic disease on top of that. She also has alupus myocarditis. So she's a really sick lady, unfortunately. She's coming with sepsis due to an unknown source. Her temp is 103, she's tachycardic, she's tachypnic. Her labs are notable actually for a profound anemia with the hemoglobin of 4.5 down from her last hemoglobin of 7.4. She's assessed, you do a fast exam, no evidence of bleeding. You also note though that her EF is 20%. You look up at the monitor, you see that chersatz are decreased from where you'd expect. You then get an arterial blood gas, and you note that her ABG sat is low there too. So it's really the sat is in fact low. You also at the same time happen to get a venous blood gas, actually a mixed venous blood gas in this particular case because this patient is in shock, you float out of the swan, you're trying to figure out what's going on. And your SVO2 is 40%. So Nick, this sounds like a pretty sick lady and things are further complicated by this hypoxemia. How can we put this together? Can we paint a coherent picture for us? - Absolutely, so this is the sixth cause, low mixed venous oxygen. And so the physiology to understand here is, remember we said that under normal conditions, your sats are like 95 to 100 arterial, and then oxygen gets extracted, blood goes back to the lungs, and the sats are now about 70 to 75%. That's a normal mixed venous oxygen sat. And your lungs are able to go from a sat of 70 to 75, up to like 95 to 100. But if your mixed venous sat drops super duper low, your lungs will not be able to braze it all the way anymore. And so in this case, this four unfortunate woman has got kind of a perfect storm of reasons that are gonna cause her to have a very low mixed venous oxygen sat. So first off, she's anemic. Her oxygen content is low because her hemoglobin is really low. Second, she's got Lupus Myocarditis and she's got any of 20%. So her cardiac output is low. Remember, those are two big factors that go into DO2. Third, her temp is 103 degrees Fahrenheit. This is an often overlooked reason, but for every one degree Celsius increase in temperature, you increase your oxygen consumption by about 15%. So her oxygen consumption is probably about 45% higher than baseline. So she's got a lot wrong here. She's not carrying a lot of oxygen. She's extracting a lot of oxygen and she's not pumping the blood very effectively. So lots of things are driving down her mixed venous. - Man, okay, yeah. So definitely a pretty complicated case. And I'm glad that you brought up that element of fever control. So we've talked a little bit about animal physiology earlier in this episode. Is there any relevant animal physiology you wanna take a moment to discuss here? - Oh boy, there's a lot of fun animal physiology here. So first off, I mean, you can actually see this physiology in like race horses, right? So when race horses run really, really fast, they'll actually drop their sats because they're extracting so much oxygen, their lungs actually can't keep up with it. And occasionally in really elite human athletes, you can see that too. But there's another really awesome one. So I said in every species, in every vertebrate, when your temperature goes up, your oxygen increases. That's not really true, there's one exception. And whenever you have one exception to a rule, you know it's gonna be the one, right? So the exception here is sloths. Sloths are, you know, those lovable species from, they hang out in trees, they hang upside down. And for whatever reason, they have this funny thing where their VO2 actually decreases with increasing temperature. So it's apparently a strategy they use to avoid hyperthermia, that the hotter they get, the less oxygen they use, the opposite of every other vertebrate on earth. - Ha, well that's, yeah, again, maybe not super germane to our day-to-day practice, but cool physiology nonetheless. - There's other cool sloth things, maybe very quickly, I'll just say that, you know, anyone who's watch Zootopia knows that sloths move very slowly. They also have a very slow gut transit time. They only, they only, they only stool about once a week. And when they do, they lose about a third of their max. They're also the only vertebrate that doesn't float. And so they actually exhale methane, which is kind of gross. - Yeah, well, I'll try not to befriend any sloths. So one other thing here, you know, we talked about this a little bit, Nick, in pre-recording, but the AA difference is kind of interesting here too. So, you know, I think I wasn't able to find a ton of literature kind of discussing this, but I think physiologically, it would make sense that the AA difference should be increased in these folks. So the PAO2, the P big AO2 should be normal because there really isn't an issue in terms of their ability to get appropriately enriched oxygen into their LVLI. But because the oxygen content of blood returning to the right heart is so low, the resultant hypoxemia should actually manifest as an increase in the AA difference. So their PAO2 should by definition be reduced because of how low that oxygen content is in the blood entering the right heart. - Yeah, I think you're right. And that actually, thank you for catching that. I think you've persuaded me with that explanation that I got to fix that error in my one page or something. - Yeah. - Thank you. - Yeah. - I think just to sort of book end this case 'cause this is an important case to sort of remember, this is somebody where they're hypoxic because they have low oxygen content, low oxygen delivery and increased consumption. So we should fix all of those things. We can use transfusions to improve oxygen content. We could consider ionotropes to improve cardiac output and therefore your oxygen delivery. And then we can also use antipyredics or actually just cooling, like surface cooling with ice to try to decrease that BO2. And often we forget that, but sometimes people are working hard on the ventilator. They're more hypoxic than they need to be because we're failing to control their temperature. Temperature control is a great strategy when you're trying to optimize oxygen delivery. - Awesome. Well, Nick, we've covered a ton here. I think we probably want to take a moment to discuss a general approach to hypoxemia briefly and then maybe we can also summarize really what we've talked about today. As far as an approach to hypoxemia, I think like with everything that we do, assessing the patient first is probably going to be the best thing to do right off the bat. Check the patient, check them on it or confirm the SAT. Is it believable? Is it real? Is the SAT probe floating around on the floor? Is it actually on the patient and appropriately giving you a good reading? You're going to want to check the history. Consider your pre-test probabilities. What's most likely going on? If this is a packupatient who just came out, got a lot of sedation, think about hypoventalation versus if this is a patient with known COPD who's coming in and has an ammonia, you might have some component of shunt and dQ mismatch in that case. You're going to want to consider getting an arterial blood gas if you think it would be helpful to confirm or to calculate the AA difference. But that's not always necessarily something you need to do, especially if the patient responds quickly to therapy and if they have a pretty good story based on your exam and your history. The other things I'd say is consider getting a chest x-ray or a bedside ultrasound to look at the lungs, consider a CTP, if PE is on the differential. And we've kind of alluded to this a few times now, but try putting on some supplemental oxygen. A lot of times we have to treat first and then we can figure out what's going on on the back end. So I would not withhold supplemental oxygen. And similarly, if you do get a blood gas, remember to look for hypercapnia or hypercarbia because that might suggest there's more than meets the eye going on and it would probably change your strategy from an oxygenation standpoint in the sense that you might put on some positive pressure as well. - Absolutely, remember that oxygen is not just a therapy, it's also kind of diagnostically useful to see what their response is. Somebody who responds well to oxygen sort of suggests some ideologies whereas somebody who fails to respond to even a lot of supplemental oxygen kind of strongly points you towards shunt. So you just see what their responses can be super valuable. We covered a ton of great physiology today. It was really fun, did some great cases. Maybe we should summarize by kind of getting some of the key points here just to sort of like book ended for our listeners. - Yeah, I think so. So first off, please, please remember that you can be hypoxic without being hypoxemic and you can be hypoxemic without being hypoxic. So these are two different terms we don't want to entangle them. And also on that note, recall that anemic, cytopathic and ischemic hypoxia, those are really the cases where you can see tissue hypoxia without hypoxemia. And while these are rare relative to hypoxemic hypoxia, they need to be considered in the appropriate patient. So don't forget about them. Or board exam. - Fair enough. - And second, remember the six causes of hypoxemic hypoxia and remember that by using the AA difference, looking at the PACO2 and the response to supplemental oxygen, you can often narrow it down. It's very helpful to understand the why behind the physiology because it'll clue you in on some of these interesting edge cases we talked about like the person who's shunting because they were put on calcium channel blockers or nitrates. And it's also really important to think about things like dead space in PE. The physiology can give you lots of useful hints and can help you avoid mistakes. - And the last point I'll make is really, in the ICU for sure, but really in a lot of medicine, inpatient outpatient, one of the key fundamental things we do for our patients is optimize oxygen delivery. And that is, I just really can't stress that enough. - It's all about oxygen. (dramatic music) - All right, so today we discussed hypoxia and hypoxemia and all their glory. If you want to learn more, you should definitely check out our show notes on the website, www.criticalcaretime.com. Nick also has a great one-pager that sums this up, so we'll make sure to link to that. We also plan on launching our newsletter soon, so please take a moment to subscribe for a mailing list and also while you're there, leave us a comment. - We read them, we love them. Yeah, thanks for that. Thanks for the shout out about the one-pager. Yeah, you should go to our website, you should check all that out. I want to say thanks for a couple other things too, while we're talking about it. Thanks to all the kind people who left us reviews and comments and shout outs. We read what you write and we listen to you and we did a whole episode based on what you said. Hope you liked our show. If so, please subscribe, give us a like, five star rating, please, on your favorite podcast app. And keep your feedback coming. We'd love to hear from you. You can tweet @critcaretime or individually @nickamark or @askinsunderscoreraiser. Follow us on Instagram, threads, and subscribe to us on YouTube. - Perfect. We'd also like to take this opportunity to thank our sponsor, C-Star Medical. We're fortunate and very grateful that this episode and all episodes of season two of Critical Care Time are sponsored by C-Star Medical. C-Star Medical is advancing the science of self-directed extracorporeal therapy to help restore the balance of a distributed immune system in a Q-Kitty injury and sepsis. Check out their website, www.cstarmedical.com to learn more. - And before we go, we want to say thanks to all the incredible members of our podcast team who make this show possible. We edit out all of our silly ooms and a's and mistakes. Also, I want to thank Kurt Bellnap for our awesome theme music, what you're hearing right now. - And finally, disclaimers. So the views expressed within this podcast and any associate media do not necessarily reflect the views of our employers, all references to patients, or encounters have been modified to be a compliant and thus any similarities to real world cases are purely coincidental. Finally, this podcast is for educational and entertainment purposes only and should not be used in lieu of seeking medical advice. With that, thanks again for listening. I once again, Dr. Cyrus Asken. And I'm Nick Mark. Thanks so much for listening. See you guys soon. (upbeat music)