WEBVTT - Ep 115 Altitude Sickness: Balloons though? 0:00:00.200 --> 0:00:02.560 I come to the fatal hour, when we were about 0:00:02.600 --> 0:00:06.479 to be seized by the terrible influence of the atmospheric decompression. 0:00:07.200 --> 0:00:10.119 At seven thousand meters, we were all standing in the basket, 0:00:10.560 --> 0:00:14.480 civil numbed for a moment, has revived. Crochet Spinelli is 0:00:14.560 --> 0:00:17.279 motionless in front of me. Look, he says to me, 0:00:17.360 --> 0:00:21.760 how beautiful those serous clouds are. The sublime spectacle before 0:00:21.800 --> 0:00:26.320 our eyes was indeed beautiful. Towards seven thy five hundred meters, 0:00:26.400 --> 0:00:30.840 the numbness one experiences is extraordinary. The body and the 0:00:30.880 --> 0:00:36.160 mind weaken little by little, gradually, unconsciously, without one's knowledge. 0:00:36.840 --> 0:00:40.320 One does not suffer at all. On the contrary, one 0:00:40.360 --> 0:00:43.519 experiences inner joy, as if it were an effect of 0:00:43.560 --> 0:00:47.920 the inundating flood of light. One becomes indifferent. One no 0:00:48.000 --> 0:00:51.040 longer thinks of the perilous situation or of the danger. 0:00:51.640 --> 0:00:55.480 One rises and is happy to rise. Vertigo of lofty 0:00:55.520 --> 0:00:58.360 regions is not a vain word, but as far as 0:00:58.360 --> 0:01:01.480 I can judge by my personal impress rushians this vertigo 0:01:01.560 --> 0:01:08.440 appears at the last moment. It immediately precedes annihilation, sudden, unexpected, irresistible. 0:01:09.200 --> 0:01:09.440 Soon. 0:01:09.560 --> 0:01:11.920 I wanted to seize the oxygen tube, but could not 0:01:12.040 --> 0:01:15.440 raise my arm. My mind, however, was still very lucid. 0:01:15.840 --> 0:01:18.360 I was still looking at the barometer. My eyes were 0:01:18.400 --> 0:01:21.160 fixed on the needle, which soon reached the pressure number 0:01:21.319 --> 0:01:24.760 of two ninety, then two eighty, beyond which it passed. 0:01:25.520 --> 0:01:28.400 I wanted to cry out, we are at eight thousand meters, 0:01:28.800 --> 0:01:32.440 but my tongue was paralyzed. Suddenly I closed my eyes 0:01:32.480 --> 0:01:37.080 and fell inert, entirely losing consciousness. It was about one thirty. 0:01:37.880 --> 0:01:40.920 At about three thirty, I opened my eyes again. I 0:01:40.959 --> 0:01:45.039 felt numb, weak, but my mind was active. The balloon 0:01:45.160 --> 0:01:49.080 was descending with terrifying speed. Syville's face was black, his 0:01:49.200 --> 0:01:53.080 eyes dull, his mouth open and full of blood. Crochet's 0:01:53.120 --> 0:01:56.240 eyes were half shut and his mouth bloody. The shock 0:01:56.320 --> 0:01:59.600 as we struck the ground was extremely violent. It was 0:01:59.640 --> 0:02:02.320 four clock. As I set foot on the ground, I 0:02:02.400 --> 0:02:05.720 was seized by a feverish excitement and fainted. Growing livid, 0:02:06.400 --> 0:02:08.120 I thought I was going to join my friends in 0:02:08.160 --> 0:02:11.720 the other world. However, I recovered little by little. I 0:02:11.760 --> 0:02:15.080 went to my unhappy companions, who were already cold and rigid. 0:02:15.760 --> 0:02:19.160 I had their bodies sheltered in a neighboring barn. Sobs 0:02:19.240 --> 0:02:19.680 choked me. 0:03:05.760 --> 0:03:08.320 Uh what. 0:03:09.639 --> 0:03:12.920 Yeah, a fatal balloon flight. 0:03:14.720 --> 0:03:18.400 Wow, yeah, Aaron, what will you have to tell me 0:03:18.440 --> 0:03:18.960 what that's from? 0:03:19.200 --> 0:03:23.480 Okay, So that was an account by Tissandier of the 0:03:23.520 --> 0:03:27.480 fatal balloon ride of eighteen seventy five. He and his 0:03:27.600 --> 0:03:32.080 two companions went up to past eight thousand meters, which, 0:03:32.120 --> 0:03:34.320 by the way is like over twenty six thousand feet, 0:03:34.960 --> 0:03:40.440 and they all like lost consciousness, and then their balloon 0:03:41.120 --> 0:03:45.160 went out, they crashed, and two of the three died. 0:03:46.000 --> 0:03:51.560 That is horrific mm hmmm, and also makes me so 0:03:51.880 --> 0:03:55.240 intrigued in what the history of today's episode is going 0:03:55.280 --> 0:03:59.640 to be because it is nothing like what I expected. 0:03:59.720 --> 0:04:05.240 And wow, yeah, I didn't even like it. Didn't even 0:04:05.320 --> 0:04:09.000 realize that the balloon thing would be kind of a 0:04:09.080 --> 0:04:12.680 left turn or seem like a left turn. But it 0:04:12.720 --> 0:04:15.040 is surprisingly relevant. 0:04:15.480 --> 0:04:17.720 I cannot wait to hear all about it. 0:04:19.960 --> 0:04:22.200 Hi, I'm Aaron Welsh. 0:04:21.680 --> 0:04:23.640 And I'm Erin Almon Updyke, and. 0:04:23.720 --> 0:04:25.720 This is this podcast will kill You. 0:04:26.000 --> 0:04:30.960 And today we're taking a few left turns or a 0:04:31.040 --> 0:04:32.919 sense and decense. I don't know, I tried. 0:04:34.360 --> 0:04:35.839 I appreciate the effort. 0:04:36.320 --> 0:04:39.720 To talk about altitude and altitude sickness. 0:04:40.279 --> 0:04:44.960 Yeah, yeah, I am really excited for this, especially because 0:04:45.560 --> 0:04:49.000 before starting this I had no idea what the history 0:04:49.080 --> 0:04:51.039 was going to be, and it turned out to be 0:04:51.240 --> 0:04:54.240 I think one of my favorite episodes to put together. 0:04:54.760 --> 0:04:55.279 Ooh. 0:04:55.680 --> 0:04:59.560 Also, do you remember our very first episode this season 0:04:59.680 --> 0:05:02.799 are As and I told the history of ventilators. I 0:05:02.800 --> 0:05:05.520 said at some point in that episode, gosh, I would 0:05:05.560 --> 0:05:11.039 love to tell the story of oxygen someday. Get a 0:05:11.040 --> 0:05:14.480 little teaser, maybe. 0:05:13.760 --> 0:05:14.240 Can't wait. 0:05:14.920 --> 0:05:15.640 Very excited. 0:05:17.960 --> 0:05:21.039 Yeah, it's gonna be It's gonna be really fun. I 0:05:21.080 --> 0:05:24.240 know nothing about the history of this and only really 0:05:24.720 --> 0:05:27.320 knew prior to this what I learned in like various 0:05:27.360 --> 0:05:31.560 physiology classes, so it was really fun to research. And 0:05:31.600 --> 0:05:33.360 I'm it's just going to be a fun episode. 0:05:33.520 --> 0:05:36.680 It is, and it's going to be made extra fun 0:05:37.040 --> 0:05:41.400 by the presence of a very special guest who is 0:05:41.640 --> 0:05:46.600 near and dear to our hearts, especially yours, especially mine. 0:05:47.440 --> 0:05:49.880 And that's just another little teaser. And you'll hear more 0:05:49.920 --> 0:05:52.920 about this very special guest later in the episode when 0:05:52.960 --> 0:05:57.360 they will come on to discuss some of the evolutionary 0:05:58.120 --> 0:06:02.359 aspects and current research going into altitude sickness and high 0:06:02.400 --> 0:06:03.560 altitude adaptation. 0:06:03.839 --> 0:06:07.880 Oh, I can't wait. I'm really excited about it. We do, okay, 0:06:07.920 --> 0:06:11.640 but before that, it is definitely quarantining time. 0:06:12.520 --> 0:06:14.880 Is what are we drinking this week? 0:06:14.960 --> 0:06:17.039 We're drinking high and dry. 0:06:18.120 --> 0:06:22.760 We are. You know, it was really difficult to come 0:06:22.839 --> 0:06:27.000 up with a quarantini recipe. Everyone really was. We are struggling. 0:06:28.480 --> 0:06:30.599 This is not This is one of the hardest parts 0:06:30.600 --> 0:06:33.280 of this job. Honestly it is. 0:06:33.920 --> 0:06:35.600 It used to be one of the easiest, and now 0:06:35.680 --> 0:06:39.240 it's like just scrolling through pages and pages of our 0:06:39.279 --> 0:06:40.920 past quarantinies, like. 0:06:40.920 --> 0:06:44.240 How many different times can we use this one item? 0:06:44.560 --> 0:06:44.880 A lot? 0:06:46.120 --> 0:06:50.520 Yeah, So we wanted to make this a dry a 0:06:50.560 --> 0:06:54.920 cocktail as possible, so that means as little sugar as possible, 0:06:54.960 --> 0:06:58.279 and so in this which is essentially a modified Paloma, 0:06:58.720 --> 0:07:01.440 we have tequila, we have grapefruit juice, we have a 0:07:01.440 --> 0:07:05.320 little bit of blood orange juice, and we're topping it 0:07:05.400 --> 0:07:09.000 with an egg white foam, you know, for that aeration. 0:07:09.640 --> 0:07:10.000 Get it. 0:07:14.680 --> 0:07:15.840 That's so funny. 0:07:16.200 --> 0:07:22.480 We We will post the full recipe for the quarantiney 0:07:22.600 --> 0:07:25.920 as well as the non alcoholic plus see Burta on 0:07:25.960 --> 0:07:28.440 our website This podcast will Kill You dot com as 0:07:28.480 --> 0:07:31.000 well as on all of our social media channels. 0:07:31.160 --> 0:07:33.920 Our website, this podcast will kill You dot com. It's 0:07:33.920 --> 0:07:35.800 a really great website that has a lot of stuff 0:07:35.800 --> 0:07:37.400 on it, So you should go there and check it out. 0:07:37.800 --> 0:07:41.560 You should, you shouldn't. That's all that needs to be said. 0:07:41.680 --> 0:07:46.480 Any other business, Eric, you know, I don't think so okay, Well, 0:07:46.560 --> 0:07:49.600 I have lots of questions about the history of this, 0:07:49.720 --> 0:07:53.360 so let's start with, you know, the biology. 0:07:54.280 --> 0:07:57.280 Come on, I want to hear about the biology. Yeah, 0:07:57.440 --> 0:07:59.640 we'll take a quick break, and then you can answer 0:07:59.640 --> 0:08:03.920 all my thousands of questions about the biology of altitude sickness. 0:08:04.120 --> 0:08:44.400 We'll try we'll try. 0:08:27.240 --> 0:08:32.240 So to understand the kind of disordered states that can 0:08:32.280 --> 0:08:39.200 result from ascending to or existing at high altitudes, we 0:08:39.440 --> 0:08:44.080 first have to understand what the heck actually changes at 0:08:44.160 --> 0:08:50.440 high altitude and what our normal physiologic response is to 0:08:50.679 --> 0:08:53.480 these changes. So that's how we're going to kind of 0:08:53.480 --> 0:08:55.960 divide up this section of the episode. First, we're going 0:08:56.000 --> 0:08:59.280 to talk about the environmental variables that actually change when 0:08:59.280 --> 0:09:02.319 we go to out theode, and then we'll talk about 0:09:02.360 --> 0:09:07.080 what our typical physiologic response is to those environmental changes, 0:09:07.520 --> 0:09:10.320 both in like the short term and the medium to 0:09:10.400 --> 0:09:12.400 long term, and then. 0:09:12.320 --> 0:09:15.160 We'll talk about what happens when these changes maybe. 0:09:14.960 --> 0:09:20.040 Don't work that well or don't go as planned or 0:09:20.280 --> 0:09:23.079 something along those lines. And that's when we'll get into 0:09:23.120 --> 0:09:25.640 both acute as well as a little bit of detail 0:09:25.640 --> 0:09:29.720 on chronic mountain sickness in their various forms. Sounds excellent, 0:09:30.080 --> 0:09:32.120 And one thing I will say for those who are 0:09:32.280 --> 0:09:35.600 really into the physiology part of this is, I am 0:09:35.600 --> 0:09:39.160 going to do this with like a minimum of math. Okay, 0:09:40.400 --> 0:09:44.160 the math formulas turns out don't really translate well to 0:09:44.240 --> 0:09:49.000 like podcast audio format. Okay, so really yeah, p ones 0:09:49.040 --> 0:09:53.680 and vs. Okay, let's get into it. By far, the 0:09:53.840 --> 0:09:57.680 single greatest environmental change that we see with respect to 0:09:57.960 --> 0:10:04.679 increasing altitude is a decrease in the partial pressure of oxygen. 0:10:05.200 --> 0:10:09.080 What does this actually mean? So when we ascend either 0:10:09.160 --> 0:10:14.760 up a mountain or perhaps a balloon, the barometric pressure, 0:10:14.960 --> 0:10:17.800 that is the pressure that the atmosphere exerts on our 0:10:17.840 --> 0:10:22.560 bodies declines because the mass of atmosphere above us is 0:10:22.679 --> 0:10:28.160 literally less mass, and this decline in barometric pressure leads 0:10:28.240 --> 0:10:33.040 to a decline in the partial pressure that oxygen exerts, 0:10:33.480 --> 0:10:37.840 So the air at high altitudes is the same percentage 0:10:37.880 --> 0:10:41.840 of oxygen twenty one percent oxygen, as we talked about 0:10:41.920 --> 0:10:44.080 in our Benz episode last season. 0:10:44.440 --> 0:10:45.880 That's right, But. 0:10:45.880 --> 0:10:48.360 What you can think of it as is the density 0:10:48.600 --> 0:10:53.520 of those oxygen molecules is less, so per breath you're 0:10:53.559 --> 0:10:59.720 getting less dense oxygen molecules. And as we talked about 0:10:59.760 --> 0:11:04.080 in our Ben's episode, when we inhale air, which is 0:11:04.200 --> 0:11:08.920 twenty one percent oxygen, some amount of that oxygen in 0:11:08.960 --> 0:11:13.880 that breath travels down our lungs into our alveoli and 0:11:13.960 --> 0:11:17.559 has to diffuse across our alvoli into our bloodstream, into 0:11:17.600 --> 0:11:22.240 our capillaries. And the transfer of this oxygen into our 0:11:22.240 --> 0:11:27.120 blood stream is determined in part by its partial pressure gradient, 0:11:28.040 --> 0:11:31.760 by how much pressure it's exerting in our alveoli relative 0:11:31.840 --> 0:11:36.160 to our capillaries. So if this partial pressure declines, which 0:11:36.160 --> 0:11:39.640 we know it does as we ascend in altitude, that 0:11:39.679 --> 0:11:45.040 means that we are transferring less oxygen into our bloodstream. 0:11:45.120 --> 0:11:48.920 So in short, what we see is less density, less 0:11:48.960 --> 0:11:52.240 pressure of oxygen in the air, which leads directly to 0:11:52.400 --> 0:11:56.520 less oxygen making it into our bloodstream, which is called hypoxemia. 0:11:57.480 --> 0:12:00.320 Then what we see is less oxygen in our tissue choose, 0:12:00.360 --> 0:12:05.120 which is called hypoxia. Sometimes people use the terms hypoxemia 0:12:05.360 --> 0:12:13.079 and hypoxia interchangeably, they're technically different things. Anyways, icy you 0:12:13.160 --> 0:12:17.520 nerds will love that little titbit. Okay, But obviously in 0:12:17.559 --> 0:12:22.080 any case, this is not great because our cells and 0:12:22.160 --> 0:12:25.480 our tissues do rely on oxygen to make energy and 0:12:25.480 --> 0:12:30.520 to function. So luckily, our body has a lot of 0:12:30.600 --> 0:12:35.839 compensatory mechanisms that it uses when we ascend to altitude 0:12:36.400 --> 0:12:38.440 or in other words, when we are faced with what's 0:12:38.480 --> 0:12:44.520 often called hyperbaric hypoxymic or hyperbaric hypoxic situations that means 0:12:44.760 --> 0:12:52.120 low pressure, low oxygen situations. This process is known as acclimatization, 0:12:52.640 --> 0:12:55.840 and it has several steps that occur both in like 0:12:55.880 --> 0:12:59.600 a very short term and a longer period like days 0:12:59.640 --> 0:13:05.920 to week timeframe. Let's get into it so first, involuntarily, 0:13:06.240 --> 0:13:09.680 All of these are involuntary. We're not conscious of these 0:13:09.720 --> 0:13:15.400 things happening. But most quickly, the change that we see 0:13:15.600 --> 0:13:19.280 as we ascend an altitude is that we see an 0:13:19.400 --> 0:13:23.599 increase in ventilation. So basically, because of this drop in 0:13:23.679 --> 0:13:27.840 partial pressure, you have less oxygen diffusing into our capillaries 0:13:27.880 --> 0:13:31.840 and arteries. What happens then, is that this decrease in 0:13:31.880 --> 0:13:37.360 oxygen leads to the stimulation of chema receptors in our aorda, 0:13:37.400 --> 0:13:39.839 which comes off of our heart, as well as our 0:13:39.880 --> 0:13:43.600 carotid arteries that go up to our brain. There are 0:13:43.679 --> 0:13:47.320 receptors in these vessels whose job it is is to 0:13:47.360 --> 0:13:50.440 sense how much oxygen there is in our blood and 0:13:50.480 --> 0:13:55.880 then stimulate our brain to fluctuate the depth and the 0:13:55.960 --> 0:13:57.040 rate of our breathing. 0:13:57.640 --> 0:13:59.199 That is so cool. 0:13:59.320 --> 0:14:04.079 It's so cool because it is entirely involuntary. It's not 0:14:04.200 --> 0:14:07.480 like if you go up to altitude you'll sit there 0:14:07.520 --> 0:14:09.960 feeling like you need to take deep breaths. This is 0:14:10.000 --> 0:14:14.480 an involuntary response that's just happening. Yeah, it's called the 0:14:14.559 --> 0:14:19.320 hypoxic ventilatory response, and we'll get into that a little 0:14:19.360 --> 0:14:21.840 bit more later, but let's keep going because that's just 0:14:21.880 --> 0:14:26.240 the first of like a cascade of changes. So first 0:14:26.480 --> 0:14:31.120 we start breathing deeper and faster. What that does is 0:14:31.160 --> 0:14:35.120 it ends up lowering the amount of carbon dioxide in 0:14:35.360 --> 0:14:38.600 our alveoli. You can essentially think of it as we're 0:14:38.640 --> 0:14:43.600 breathing off extra carbon dioxide as we breathe like this, 0:14:44.880 --> 0:14:49.640 and that helps to increase the partial pressure of oxygen 0:14:49.840 --> 0:14:53.520 because they are inversely related in our ALVOLI. 0:14:53.400 --> 0:14:55.600 How are we doing that. 0:14:55.600 --> 0:14:59.320 That's just like a matter again of mathematics. 0:14:58.920 --> 0:15:02.280 Okay, just like properties of gases and behaviors of gases. 0:15:02.360 --> 0:15:05.080 Okay, yeah, So it's not like changing the concentrations, it's 0:15:05.120 --> 0:15:08.840 just changing the partial pressures. By blowing off more CO two, 0:15:09.240 --> 0:15:12.960 you have an increased pressure of oxygen. So what that 0:15:13.000 --> 0:15:17.120 does is allow our capillaries to continue extracting to maintain 0:15:17.240 --> 0:15:20.960 a steeper gradient for the diffusion of oxygen into our capillaries, 0:15:21.000 --> 0:15:24.080 which is what we need because there's less pressure of 0:15:24.120 --> 0:15:27.560 oxygen from the atmosphere itself. It's so cool, I know, 0:15:27.640 --> 0:15:30.520 I know, it keeps going, It keeps going. At the 0:15:30.600 --> 0:15:34.520 same time, this reduction in carbon dioxide that we see 0:15:34.840 --> 0:15:38.800 also leads to what we know of as a respiratory alkalosis, 0:15:39.440 --> 0:15:42.400 because carbon dioxide, as I'm pretty sure we talked a 0:15:42.440 --> 0:15:45.960 lot about in our Benz episode, in our bloodstream results 0:15:46.000 --> 0:15:49.080 in acidification, so's you can think of it as an acid. 0:15:49.640 --> 0:15:52.840 So if we're blowing off carbon dioxide now we have 0:15:52.880 --> 0:15:56.760 an increase in the pH of our blood, which is alkalosis. 0:15:58.120 --> 0:16:03.080 If this happens at sea level. Like when we hyperventilate 0:16:03.120 --> 0:16:07.040 at sea level, our brain would try to compensate for 0:16:07.120 --> 0:16:11.200 this change in pH that we see to actually inhibit 0:16:11.240 --> 0:16:16.200 our respiration. But at altitude, this process is maintained by 0:16:16.280 --> 0:16:21.960 this hypoxic ventilatory response by those chemo receptors we already mentioned, 0:16:22.040 --> 0:16:27.520 and additional chemo receptors in our brain to continue these 0:16:27.640 --> 0:16:31.520 high levels of ventilation because we're specifically facing lower partial 0:16:31.560 --> 0:16:34.200 pressure of oxygen in this setting. 0:16:35.640 --> 0:16:40.160 So hyperventilation at sea level is different than the hypoxic 0:16:40.240 --> 0:16:45.880 ventilatory response, it sure is, arin what how like? So 0:16:46.080 --> 0:16:51.880 is this those specific chemoreceptors that are only activated at altitude? 0:16:52.240 --> 0:16:54.960 So no, it's not that they're only activated altitude, but 0:16:55.000 --> 0:16:58.560 they're being activated in part by this lowered partial pressure 0:16:58.600 --> 0:17:02.880 of oxygen and then in combination with this response, the 0:17:03.000 --> 0:17:06.000 changes in alkalosis. So it's more like a combination of 0:17:06.040 --> 0:17:11.119 all of these factors rather than a pure hyperventilation that 0:17:11.160 --> 0:17:14.120 you see at sea level without all of the additional factors. 0:17:14.160 --> 0:17:17.320 If that makes sense. Yes, Okay, altitude is not necessarily 0:17:17.320 --> 0:17:19.640 the only place that you would see this happen, but 0:17:19.800 --> 0:17:21.680 this is what happens at altitude. 0:17:21.720 --> 0:17:23.800 So Aaron. Where else would we see this happen. 0:17:24.359 --> 0:17:27.280 So there have been other studies that, look, we'll get 0:17:27.320 --> 0:17:28.959 into it a little bit more later, but at like 0:17:29.400 --> 0:17:33.920 is it the pressure changes or is it just the hypoxia, 0:17:34.040 --> 0:17:36.240 But so really it's it seems that a lot of 0:17:36.280 --> 0:17:38.840 it is driven by the hypoxia initially. 0:17:39.560 --> 0:17:39.800 Yeah. 0:17:40.119 --> 0:17:40.359 Yeah. 0:17:41.040 --> 0:17:43.600 So the next part of what we see because of 0:17:43.600 --> 0:17:48.560 this respiratory alkalosis is that this naturally triggers our kidneys 0:17:48.720 --> 0:17:53.679 to try and compensate by peeing off more base in 0:17:53.720 --> 0:17:58.679 the form of bicarbonate, so we resorb less by carbonate 0:17:58.760 --> 0:18:01.720 and that is actually just a normal physiologic response to 0:18:01.760 --> 0:18:06.080 a respiratory alkalosis. That's how we compensate, okay, And that 0:18:06.119 --> 0:18:09.320 happens kind of a slightly longer time frame than the 0:18:09.359 --> 0:18:12.439 respiration part of it, So that I know, was like 0:18:12.680 --> 0:18:14.880 a lot of different I loved it. 0:18:15.520 --> 0:18:16.160 I'm thrilled. 0:18:16.640 --> 0:18:18.960 But basically, to sum it up, in short, we have 0:18:19.000 --> 0:18:21.919 a decrease in the partial pressure of oxygen, which is 0:18:22.040 --> 0:18:25.359 less oxygen in our arteries. That triggers our brain to 0:18:25.440 --> 0:18:29.600 breathe deeper and faster to then breathe off more carbon 0:18:29.640 --> 0:18:33.800 dioxide and allow more oxygen to diffuse into our arteries 0:18:33.880 --> 0:18:40.120 so that we maintain good oxygen concentration. But that's not all, 0:18:40.960 --> 0:18:44.000 of course, not because oxygen in our bloodstream is not 0:18:44.359 --> 0:18:49.000 just dissolved in our bloodstream like a gas. In fact, 0:18:49.440 --> 0:18:52.800 nearly all of the oxygen in our bloodstream is bound 0:18:52.960 --> 0:18:56.159 to a pretty important protein that everyone's probably heard of 0:18:56.520 --> 0:19:01.160 on our red blood cells, aka hemoglobin. So the next 0:19:01.240 --> 0:19:06.080 bit of the acclimatization process involves hemoglobin, and this part 0:19:06.119 --> 0:19:09.800 takes a little bit more time. So the respiratory response 0:19:09.880 --> 0:19:13.359 is starting immediately as we ascend, but within one to 0:19:13.440 --> 0:19:16.520 two days of ascent to altitude, what we see is 0:19:16.560 --> 0:19:20.840 a rise in the concentration of hemoglobin. Hemoglobin is the 0:19:20.840 --> 0:19:25.119 protein that's binding and carrying oxygen and then delivering it 0:19:25.160 --> 0:19:30.040 to our tissues. And that's important, binding oxygen and then 0:19:30.320 --> 0:19:32.119 releasing it and delivering it. 0:19:32.680 --> 0:19:36.320 Oh okay, I could tell that's like sort of a 0:19:36.520 --> 0:19:38.560 remember this because it's going to come back later. 0:19:38.760 --> 0:19:40.200 Is that like this is on the test. 0:19:40.800 --> 0:19:42.440 It's exactly on the test camelt. 0:19:45.200 --> 0:19:47.480 So within one to two days we see a rise 0:19:47.560 --> 0:19:51.560 in the concentration of hemoglobin. And this happens because the 0:19:51.680 --> 0:19:56.360 volume of our plasma in our blood actually falls up 0:19:56.359 --> 0:19:59.840 to fifteen to twenty five percent, which is a phenomenon 0:20:00.119 --> 0:20:04.600 out And this happens primarily via like a gentle diarysis. 0:20:04.600 --> 0:20:09.800 We start peeing off more fluid to decrease the plasma 0:20:09.880 --> 0:20:13.320 volume and then increase the concentration of hemoglobin. 0:20:13.720 --> 0:20:19.560 Okay, a question here about altitude. Yeah, at what point 0:20:19.840 --> 0:20:21.119 do these things happen? 0:20:21.480 --> 0:20:26.000 This is such a good question. There's no threshold, there's 0:20:26.040 --> 0:20:30.400 gradients because as you ascend, the partial pressure falls, right, 0:20:30.640 --> 0:20:36.080 just no matter what. But when we look at, for example, 0:20:36.280 --> 0:20:40.920 dysfunction in this process, we don't tend to see altitude 0:20:41.119 --> 0:20:45.520 sickness until we're getting pretty high, like twenty five hundred 0:20:45.560 --> 0:20:48.840 meters or about eight thousand feet. Sometimes we can see 0:20:48.840 --> 0:20:52.960 it at slightly lower altitudes, but I don't think from 0:20:53.000 --> 0:20:55.600 what I have read, there's not like an altitude at 0:20:55.640 --> 0:21:00.280 which you see respiratory compensation starts versus stops. It's just 0:21:00.320 --> 0:21:02.080 a kind of gradual process. 0:21:02.560 --> 0:21:06.359 But is there a proportional response to altitude, Like do 0:21:06.440 --> 0:21:09.440 you lose less plasma if you go up only twenty 0:21:09.440 --> 0:21:12.159 five hundred meters compared to five thousand meters. 0:21:12.600 --> 0:21:16.760 Yeah, that's a good question. I don't know. I didn't 0:21:16.840 --> 0:21:20.080 see that in the studies that I read. We can 0:21:20.119 --> 0:21:21.399 ask our guests. 0:21:21.520 --> 0:21:26.879 Okay, I'll note it down, Yeah. 0:21:25.240 --> 0:21:27.879 Because I think that would be really interesting, especially I 0:21:27.920 --> 0:21:31.440 think we'd have more data on that in animals than 0:21:31.440 --> 0:21:34.879 we do in humans. Because what I will say about 0:21:35.040 --> 0:21:38.879 this whole process that we've learned about the acclimtization process 0:21:39.520 --> 0:21:41.960 is that it tends to be studied once we get 0:21:42.000 --> 0:21:45.479 to an altitude at which you're at risk for acute 0:21:45.520 --> 0:21:49.199 mountain sickness, so above that twenty five hundred meters usually, 0:21:50.160 --> 0:21:54.520 and then studied in people depending on how quickly they 0:21:54.560 --> 0:21:57.560 go up versus how slowly they continue to ascend, if 0:21:57.560 --> 0:22:01.359 that makes sense. Yeah, okay, But that's the first step 0:22:01.440 --> 0:22:05.280 of this next process. Reduction in plasma volume, increase in 0:22:05.320 --> 0:22:09.720 concentration of hemoglobin. This is actually a relatively short lived 0:22:10.640 --> 0:22:15.280 phenomenon that we see because then what happens over the 0:22:15.280 --> 0:22:20.600 next period of days two weeks is that this triggers erythropotin, 0:22:20.720 --> 0:22:24.320 which is one of the major things that we make 0:22:24.440 --> 0:22:28.360 to stimulate red blood cell production. So what we see 0:22:28.440 --> 0:22:32.360 is an increase in red blood cell production, and then 0:22:32.480 --> 0:22:35.439 over the course of days two weeks, to a month 0:22:35.600 --> 0:22:40.200 or two, our total red blood cell mass will actually 0:22:40.440 --> 0:22:46.240 increase overall. So if you're at altitude for less than 0:22:46.280 --> 0:22:48.320 a week, you're not going to see all of this 0:22:48.400 --> 0:22:51.359 play out. This is something that happens over the course 0:22:51.400 --> 0:22:56.639 of time. But here's why this gets to be so important, 0:22:57.400 --> 0:23:01.879 because there's also this thing in physiology called the oxygen 0:23:02.080 --> 0:23:07.040 dissociation curve that people might have heard of. This is 0:23:07.080 --> 0:23:12.040 a measure of both how tightly our hemoglobin binds this oxygen, 0:23:12.240 --> 0:23:15.800 like how much of an affinity it has for grabbing 0:23:16.240 --> 0:23:19.800 and becoming fully saturated with oxygen, which it has to 0:23:19.840 --> 0:23:25.679 do in our lungs, and also how readily it gives 0:23:25.760 --> 0:23:30.640 up its oxygen at the level of our tissues. Ah, 0:23:30.720 --> 0:23:34.720 because both of these parts of hemoglobin are really important, 0:23:34.760 --> 0:23:37.200 there has to be a balance between grabbing and holding 0:23:37.240 --> 0:23:40.000 all that oxygen and then letting it go when we 0:23:40.040 --> 0:23:43.600 need to let it go. So what's really cool about 0:23:43.640 --> 0:23:47.720 this acclimatization process is that we see effects on both 0:23:48.000 --> 0:23:52.520 levels of this oxygen dissociation curve. What we see is 0:23:52.520 --> 0:23:56.320 that the increase in blood pH that I mentioned from 0:23:56.320 --> 0:24:03.200 that respiratory alkalosis shifts this oxygen curve such that hemoglobin 0:24:03.280 --> 0:24:08.320 has a greater affinity for oxygen, so under alcoholic conditions, 0:24:08.359 --> 0:24:11.520 a greater pH hemoglobin's like, ah, I need that oxygen. 0:24:11.600 --> 0:24:13.200 Give it to me. I'm gonna grab it and hold it. 0:24:13.240 --> 0:24:17.640 And it gets really efficient at that. But in addition 0:24:17.720 --> 0:24:21.240 to what I mentioned about just increasing overall hemoglobin mass, 0:24:21.280 --> 0:24:23.639 the other thing that we see our red blood cells 0:24:23.760 --> 0:24:28.440 making more of as we acclimatize is a substance called 0:24:28.600 --> 0:24:34.639 two three bpg okay or two three biz phosphogelyceiric acid. 0:24:34.720 --> 0:24:39.880 No one cares. This is something that helps our hemoglobin 0:24:40.240 --> 0:24:45.720 actually have a decreased affinity for oxygen or an increase 0:24:45.800 --> 0:24:49.520 in the ability of our hemoglobin to offload oxygen at 0:24:49.520 --> 0:24:52.760 the level of our tissues. And these two processes work 0:24:52.880 --> 0:24:57.119 together rather than canceling each other out right, so that 0:24:57.320 --> 0:25:01.959 we have hemoglobin that becomes more efficient at grabbing oxygen 0:25:02.800 --> 0:25:05.280 under conditions which it needs to, which is in our 0:25:05.359 --> 0:25:08.240 lungs when that partial pressure dictates that it needs to 0:25:08.240 --> 0:25:11.920 grab oxygen, and better at offloading it at the level 0:25:11.920 --> 0:25:14.600 of our tissues when the gradients are dictating we need 0:25:14.640 --> 0:25:19.119 to offload this oxygen very cool. Those are the major 0:25:19.280 --> 0:25:22.840 processes of acclimatization. We see them in the short term, 0:25:22.960 --> 0:25:25.600 mostly with respiration. We see them in the long term 0:25:25.720 --> 0:25:30.920 with these changes in hemoglobin. We do also see, especially 0:25:30.960 --> 0:25:34.119 in the very short term, like within twenty four hours 0:25:34.200 --> 0:25:38.280 of ascending two altitudes above twenty five hundred meters. As 0:25:38.320 --> 0:25:41.760 most of our data, we see an increase in cardiac 0:25:41.840 --> 0:25:45.880 output and heart rate, which is thought to be related 0:25:45.920 --> 0:25:50.879 to increases in our sympathetic nervous system activity. Because of 0:25:50.920 --> 0:25:56.920 this initial hypoxia, this part the increase in cardiac output 0:25:57.200 --> 0:26:00.960 tends to normalize over a period of days, and then 0:26:01.040 --> 0:26:04.800 what we actually can see is a decrease in stroke volume, 0:26:04.920 --> 0:26:08.240 or the amount of blood that each heartbeat pushes out, 0:26:08.760 --> 0:26:13.720 because of that decrease in plasma volume, which is really interesting, huh. 0:26:13.760 --> 0:26:16.240 And then we also see changes that happen at the 0:26:16.320 --> 0:26:21.560 level of our vasculature. So like our blood vessels in 0:26:21.600 --> 0:26:27.240 some cases might vasodilate to allow blood to push more 0:26:27.280 --> 0:26:31.879 oxygen to our tissues, but in our pulmonary vasculature, so 0:26:31.960 --> 0:26:35.000 the blood vessels in our lungs, we often can see 0:26:35.040 --> 0:26:39.240 a vasoconstriction that happens because of the decrease in the 0:26:39.280 --> 0:26:43.320 concentration of oxygen, and so this is kind of like 0:26:43.359 --> 0:26:47.080 a balance that our body has to do. And we'll 0:26:47.080 --> 0:26:49.439 get into what can happen when maybe that doesn't go 0:26:49.960 --> 0:26:53.639