From the Vault: Thirst, Part 2

What are you drinking right now? Absolutely nothing? Oh no, wait, I do have I have water here at my desk. Water. I'm always drinking water. I'm a water guy. You know, some people are really into tea. I almost never drink tea. I go coffee water. That That's pretty much it during the daytime hours at least. Oh yeah, well, I'm currently drinking tea. I generally go coffee tea, tea, water tea, and then water, and then when the evening comes, you know,

maybe I'll have something something else to drink. But yeah, right now it is tea, which is essentially water but with extra things added to it. You know, I sometimes get confused about what tea means because I think of tea as being a specific kind of plant, Like, isn't there a tea tree? Again, I don't know much about tea,

so I think about it in that way. But then you can make a tea out of like anything basically that you steep in water, right, people make mushroom teas, people with all kinds of just like oh yeahs and plant stuff in water, and that's tea. Also, yeah, like I mean, there's there's proper tea, and that's generally what I'm what I'm drinking. I'm drinking, you know, a dark

tea or maybe a green tea. But also sometimes I'll have a tumeric tea, which is like like tumeric and ginger and a little coconut oil and a little honey hot water. But it doesn't actually contain tea, So it's not completely accurate to call it such, because it's sort of how not all band aids are technically band aids or xeroxis or whatever. Has this been a terrible intro, Maybe we can cut my tea thing. No, No, this is a This is an intro that the people can

relate to people are can have thoughts on this. It's always good to start off asking what a word means. So I turns out I know nothing about tea. I have no no, there you go. We need to come back and do an episode or a series of episodes

on t It's a fascinating subject, fascinating history. Okay, well, we're going to jump back into some of the science that we were talking about in the last episode, where I was reviewing an interesting paper that I had read summarizing the recent state of research on the biology of thirst. That was it was a paper published in Current Biology. We had to break off in the middle of talking about it. But but before we get back into that, Rob, I think you want to talk about the taste of water,

which I think is in itself a very interesting subject. Yeah, it's it's a strange one because we probably don't think about it enough, but but we often talk about it, especially when we when we travel from one place to another. UM we if you look back on I think back on water that you've consumed in the past, you may

have specific memories of different waters. Um Like I remember when my family lived in the country and we had well water and it had it had a distinctive taste, and I don't I can't say that I loved it, But if I were to encounter the exact same flavor profile again, it would probably make me nostalgic, you know, like it it's it's a definite flavor that is tied to a definite place and time. Warning that this is a little crude, but I don't know of how else

to explain it. You've ever been somewhere that had farty water, Um, well, it's kind of sulfury water. Yeah, it kind of kind of like water from the Yes, that's kind of what this was like. Yeah, it was that had kind of a fire and brimstone kind of flavor to it. Oh okay, that's a more elegant way to put it. Well, the denizens of Hell are not insalted. They're flatter that you would you would compare this foul drinking water two flats,

uh huh. But um, you know, but then sometimes I don't know, there's there's also beech water, you know, like I anytime I'm in Florida and I'm having Florida water, like it has its own it tends to have its own bouquet, its own flavor. Profile that at the time I'm not enjoying, but then after I'm back and drinking taste your water, I'm kind of kind of long for it, you know, because like this is the water of the vacation that I am no longer on that sort of thing.

I remember when I was in like a middle school, I went to New Mexico and we went somewhere there where the water was very I don't know, the tap water was almost kind of frothy somehow. It was like a kind of kind of white and cloudy, and I remember thinking it had a strange taste. I don't know what to connect that too, if it was supposed to

be like that or not. Yeah, So I guess one thing we can definitely establish here is that there certainly seems to there is an objective difference in drinking waters from one place to another, Atlanta water versus Florida water, that sort of thing. But there's also this wide variety in how people just interpret the taste of water, you know. I think we often think of water as being neutral

or tasteless. If you're mixing a cocktail, for example, you don't want to shake it too long with the crushed ice because you will what will happen, You will water it down. Water in this case is the antithesis of

an interesting flavor profile. Well, but the other half of that is sometimes people screw up making a drink because they don't shake it with ice at all when they're supposed to, and they don't understand that shaking with ice not only cools the drink, but it also adds a certain amount of water to the drink, which is an important ingredient. Yes, absolutely so. You suppose to shake a cocktail and you don't, you end up with a drink

that's usually too strong or too sweet. Yeah, there's a balance to be maintained there, much like the balance of water in the human body that we discussed in the last episode. Many of you out there have probably met someone who claims to not like the taste of water. Sometimes these individuals will will use flavored water or other beverages instead, and we'll tend to shy away from just

drinking straight water. But I don't know if you're like me, you know, perhaps you've noticed times when a glass of ice water is just super satisfying. Um, you know, particularly on a hot day, like a just a super cold water lots of ice in it. Um I would, I would tend to. I found myself wanting to categorize that as delicious, though at the same time feeling weird for thinking that because it's like it's water. I can't say it's delicious. It has no flavor, right, that's what we believe.

Another another one I really like is the first sip of cold water that I have after I have brushed my teeth. Now, after I've brushed my teeth and rinsed and spit I'm not drinking water that way, but yeah, like, after I've brushed my teeth, I've walked into another room, I have a sip of water, super cool and refreshing. Agreed, much better than the sip of orange juice after you've brushed your teeth, which is, Yeah, I don't know if you've ever tried that, it's famously disgusting. Oh this is

this is always the worst. Really getting into the weeds here, but that that feeling when you you were you're busy in the morning, you go brush your teeth, you come back and you find your coffee cup and it still has half a cup of coffee in it. Oh, heartbreaking, because you know you can't drink it. Now. If you drink, you can drink it, you can you can throw it back,

but it's going to taste awful. I wonder if anybody's ever done a controlled study of how long you have to wait after brushing your teeth before those those horrible flavor interactions fade away. I don't think it's too long, it's yeah. I mean, if I had to venture to guess, I'd say it couldn't be more than like twenty minutes, right, Yeah, of course, a lot of this, some of this is going to vary culture to culture. In some cultures, it's not it's not considered advisable to drink cold water. You

want to drink hot water. So you know, there's it's gonna it's gonna it's gonna vary. There's a lot of cultural stuff going on here as well. Oh I've never heard of that. What's what's an example of a culture that favors hot water drinking. There's a connection if memory serves as a connection to traditional Chinese medicine here, where the idea is that it's better for your health to drink hot water as opposed to cold water. But I

don't remember any of the deeper details of regarding it all. Right, Well, to get us back on track, you had mentioned that maybe maybe it was wrong to say that tap water, you know, cold water coming in on a hot day was delicious because water itself doesn't really have a taste. And I think this is a common understanding. But is that true? Like it does it have a taste? Does it not have a taste? Does it have a taste? We're just so used to that we can't taste it anymore. Yeah,

we'll like to. Well, to go back to Aristotle, Aristotle was certainly kind of in the no taste camp, stating that it was for the most part tasteless. The idea that water is that it made liver flavors, but it's in and of itself does not have flavor. But a lot of a lot of work has gone into this this question. Uh, some some interesting studies. UM. I was reading an article by Berlin Game at All titled Understanding the Basics of Tapwater Taste, publishing the American Water Works

Association Journal in two thousand and seven. UM, and they point out that the basically you get the water is going to contain negatively and positively charged ions as minerals, you're going to find that in your tap water, and that can positively and negatively affect taste. This is especially key, they point out as far as water regulations and reverse osmoses go, which is to say, without without getting into all the chemistry, there are certain differences in water flavor

due to different minerals and other elements in the water. Now, another interesting thing about about tap water, especially generally when you're drinking tap water, the drinking water probably contains calcium, magnesium, sodium, and according to Azolae at All in an article in the Journal of General Internal Medicine from two thousand and one titled Comparison of Mineral Content of tap water and bottled waters, the mineral content of drinking water like this

ultimately may be an important source of daily recommended mineral dosages, certainly in the United States, which was the area they

were looking at here. And so basically, while we might think of water as being this thing that we would will just purify the heck out of it, just give me the purest water possible, the purest water possible isn't necessarily going to be the healthiest or the tastiest, which I thought was an interest distinction, like when when we when we purchase bottled water, we're not going and buying the distilled water usually. I mean, maybe, you know, maybe that's what you are doing, but for the most part,

people are are not buying distilled water for drinking purposes. Right. But distilled water, even though it is probably the purest form of water you can get, is not necessarily better for any reason, not for not for health or for experience of drinking. Right now, in terms of just trying to get down to the question though, well, what what does it taste like? Okay, you know, we're saying it can can go a little in this direction, a little

in that direction. We have these mineral components, uh, you know, adding to the to the flavor. But but what is the taste itself? And I think one of the interesting things about that question is that it forces you to take a step back and think about taste itself. Um, you know, taste involves both sensations on the tongue and olfactory information as well. So it's not only it's not only tasting with the mouth, it's smelling, uh whatever you

know it is that you or consuming as well. And certainly we do taste contents in the water, though under ideal circumstances that that's not going to push you hard in any direction. But obviously, if you dilute some sugar in a glass of the universal solvent and drink it, you'll find it sweet. Saltwater taste salty. Your sense of

taste is still weighing in on the water. But in terms of this kind of brings us back to the same question, does the water itself have a taste or is it just the vehicle for these various flavors, be it salt or sugar, or a slight hint of magnesium, that sort of thing. So one idea proposed in the sixties and seventies by psychologist Linda Bartschuk was that the taste of water is more of an after taste of

prior eating and drinking. And this, too, I guess, is more in line with the idea of water as the vehicle of flavor, but something that is in and of itself flavorless. So the idea would be that, like when you take a drink of water, you are somehow re experiencing flavors of foods you may have eaten most recently. Yeah, and this this will become important. And again we have to realize that when you take a sip of water, you are not introducing water. No matter how sterile your

water is, your mouth is not sterile. You know your your mouth is going to even if you if you've just brushed your teeth, great, but that you're going to have some semblance of the of that experience in your mouth. If you're eating dinner, you know there's going to be the hint of food or drink as well. So, yeah, you're not introducing the water into a neutral place. If

nothing else you your saliva is present. Emily Underwood wrote in an excellent short twenty seventeen piece for the American Association for the Advancement of Science on this topic, the Flavor of Water, And at one point she's a sighting Zachary Knight, Oh, who is one of the three authors of the research summary thirst in Current Biology that I was referring to in the last episode and I'll be

talking about again in a few minutes. Yeah, So Underwood points to something that that we discussed in the last episode that you know, ultimately, when we're getting into taste, when we're getting into water detection in the mouth, the molecular and cellular mechanisms here are not that well understood. And then she also touches on some of nights research

regarding the thirst trigger. Uh, you know where where that is seems to locate in the brain and then ultimately what's where is the trigger in the in the rest of the body. But we'll come back to that in a bit. Yeah, but I guess there are somewhat separate questions for can you detect water in your mouth versus

can you taste water? I mean those are slightly slightly different, right, yeah, well, but but then again when you start thinking about like what taste is, maybe they're not that different, like it's but but it basically comes down to, yeah, it's not about interpreting these minerals or sweetness or saltiness, but like

the just the basic signal of it is water. It is in my mouth, you know, and then ultimately being able to tell if something is not water, like or if it or if the water is you know, too far in a particular direction, like oh it is it is actually oil and water and not just water. I wanted water. That's sort of question. So research has been trying to isolate water sensing taste receptor. It sells on

the tongue of a particular note. Here is the paper The Cellular Mechanism for Water Detection in the Mammalian Taste system by Zocchi at All, published in Nature Neuroscience in

twenty seventeen. This was a team i believe from the California Institute of Technology in Pasadena, and they were working with mice and this is this is one of those the studies that I mean, it's already an interesting area, like using mice to figure out how we're tasting, but and it goes in ultimately strange directions that are pretty fascinating.

So they were they were using different varieties of mice with specific types of taste receptor cells genetically knocked out in order to try and isolate which ones were seemingly useful in tasting water. And they found that the acid sensing sour taste receptor cells seem to be the most involved. Mice with those knocked out took far longer distinguishing oily water from clean water. In the words of the study, this quote compromise discrimination between water and non aqueous fluids.

So these cells seem like they may they may well be very much involved in the process. Interesting, Okay, so if we are actually tasting water, it may rely more on the cells that normally taste sourness or acidity than other taste receptor cells, or at least in mice, And if the same held true in humans, that would be the case for us. Right. But this is where the mouse experiment from this team gets weird. So to further test this out, they bred mice that could taste light

with these acid sensing TRCs taste receptor cells. They train them to drink water from a spigot, and they replace that spigot with an optic fiber cable. So they apparently treated the mice in this case, they apparently treated the light as if they were tasting water, but they didn't stop. They kept drinking the light long after they would have

normally stopped drinking water. So the acid sensing TRCs might be involved in triggering drinking, but they might not be involved in stopping you from drinking, like saying, Okay, well, that's that's all the water I need to drink right now, and I'm not sure there may be other complications there. I mean, once you have an animal drinking light and not actual water. It just seems to me like there

might there might be other things going on there. I'll on a very physical basis, so this would be taste receptor cells in the mouth, but they're like optically sensitive cells. Am I right about this? It's literally like drinking light with their mouth, like letting light shine into the oral cavity. Yes, it h I mean, it sounds insane when you say it out loud, but but yeah, there's there's actually a YouTube video about it from Science Magazine titled these mice

are drinking light. So if anyone needs to actually see what we're talking about here, pull that up. And yeah, just it's it's a this, this black mouse going up to this um this little receptacle, and it appears to be drinking, but there's blue light flooding out of the hole, okay, and it's got light sensitive cells in its mouth, So the mouse's brain is reacting as if by shining light into its mouth it was swallowing water. Yes, that's crazy, man, Yeah it is. This is this is it's it's mind

blowing on several levels here. So ultimately this this all might be related to changes in pH level when in a normal situation, when you know, a mouse or any mammal supposedly is drinking something that is not light. When it tries out the water, saliva is washing around in the mouth, and the removal of saliva might be key to sensing water. Again, coming back to what we said earlier about you know, water is not entering into a

neutral environment when it goes in your mouth. It's going to interact with at least saliva, and in doing so that might change the pH level which triggers these these TRCs on the tongue. That seems to be the basic framework we're potentially looking at here. Oh, that's interesting. So at least according to the idea here, part of the sensation of drinking water might be the water stability to wash natural saliva out of the mouth. Right though, of

course standard caveat that. More researches quired and then we still don't We still don't have this one knocked one, but it's yeah, it's it. Ultimately, it makes you rethink again what taste actually is and consider that there may be precise triggers in place for detecting water and distinguish it from other liquids. And then also letting you know

that you have had enough water. Like all these things that we just take for granted, we think of them as we think of them as choices that we make, like I have I am, I've decided now I must have water. I have decided now that I don't need any more water. But but these are all tied into the you know, this intricate biological system. Than all right, well, rob, if you're ready, I wanted to discuss some more of the things I was reading in that twenty sixteen article

in Current Biology that was about the biology of thirst. Again. This was by David Leeb, Christopher Zimmerman, and Zachary Knight. Let's do it all right now. We already talked about some of the conditions that will trigger thirst and water seeking behavior in animals such as rodents. In humans, commonly, one thing would be a decrease in water volume in

the body. But another thing would be an increase in what's called blood osmolality osmol A L I T Y I spell it because that word will keep coming up in this discussion. Osmolality is the concentration of substances dissolved

in the water content of the body. So the blood osmolality will go up, say if you consume salt or consume other kinds of salts of various minerals, whether that's sodium or magnesium or whatever, there are lots of things dissolved in the blood, and as the concentration of those things dissolved in the blood goes up, that's known as

increasing osmolality. And as we discussed in the last episode, you your osmolality really needs to be pretty tightly constrained within an ideal range, or it can start leading to system wide problems with cellular function because cells need a pretty tightly controlled electrochemical gradient on each side of their membranes in order to control the passage of ions in and out of the cell to you know, take in things, the cell needs to release waste products and so forth.

So in order for your body to work right, it needs to have the right level of the right concentration of things like salts dissolved in its water. But you also have to keep your body, your body's water volume at the right level in order to maintain ideal blood pressure because that blood's got to flow, and if you suddenly are to remove a lot of liquid from the body, suddenly the heart has to pump harder and harder to get the red blood cells to all the different parts

of your body. So keeping up keeping up the right amount of water in the body and the correct concentration of substances dissolved in that water is crucial. And that dichotomy we talked about last time actually breaks down into two distinct types of dehydration that the authors talk about, and these two types of dehydration actually lead to different behavioral reactions in animals. So you can have dehydration within

cells or dehydration between cells. A loss of water from within cells, known as intracellular dehydration, is usually caused by high blood osmolality, so the introduction of salts or other things like that into the body. This draws water out of cells by osmosis and causes the cells to shrink, which certainly doesn't sound good. Standard behavioral response to that kind of thing that intracellular dehydration is thirst. You want water,

so you go get it. Loss of water from between cells is known as extra cellular dehydration, and this usually is caused by a loss of total blood volume, for example by bleeding. You know, if you cut yourself and lose a bunch of liquid out of your arm or something. You will lose total blood content without changing the body's osmolality. You know, you think about it that way, like you're the liquid is going down, but you're not changing how

salty the liquid that's left is. So in order to recover from that condition, you will actually need both water and salt to replenish the lost volume. Just drinking water alone would leave your osmolality too low. So the behavioral response to loss of total water content or content from between cells is usually thirst plus what the author is

called salt appetite. You want water and salt at the same time, But interestingly, many things that happen to the body cause both types of dehydration at the same time. Then the example they give is sweating. This is very common, right, you go out in the sun and you sweat. Well, sweat is not only a loss of blood volume. Sweat is salty, but sweat is actually less salty than your blood. So if your body is losing liquid that is less salty than its water content overall, like sweat is, the

salt content of what's left behind is therefore increasing. Does that make sense, So the extra salt left over inside you when you sweat causes an increase in blood osmolality, again triggering a thirst for water. It's kind of counterintuitive because if you ever do taste sweat it, you know, it tastes salty, so you would think it would feel like you're losing salt, but you're actually gaining salt is

in relationship to the amount of water left in you. Yeah, I think we've touched on this on the show before that sometimes we give too much credit to sweat in its ability to remove things from our body. Certainly when some arguments for the removal of impurities through sweat, for example, Oh yeah, yeah, right with people who think that you can like cleanse all the toxins by sweating or something.

I mean, sweating is great, no, no knocking on sweat and it memory serves like there is some toxin removal, but not not anywhere near as good as say, good old fashioned urination. I mean, that's that's right, That's why we have urination exactly. So I guess from here we go on to talk about how the brain senses and monitors osmolality. This is what the authors say is quote, probably the most important homeostatic signal for drinking in everyday

life is the brain's ability to monitor osmolality. That's what's going to be causing you to go drink water. And the authors point out some interesting things, one of which is that when blood osmolality and blood volume are both threatened at the same time, for example, if they both increase above the ideal range at the same time, the body places a higher priority on defending the ideal osmolality

than it does on defending volume. So examples of this would be, you know, hypernetremia having too much sodium, or hyperglycemia having too much glucose in the blood, whatever it is. The state of having too high of an osmolality, which they call hyper tonicity, is probably more threatening, more of a danger overall than having not quite the right amount of water volume in your body. But anyway, well, you know,

so what takes care of this whole job. Well, you've got some physical structures in your brain that sort of dip their finger into the soup to taste it for salt and let you know what's going on. Both of them are small, They reside in the forebrain, and they are known as first of all, the subfornical organ or SFO, and then the organum vasculosum of the lamina terminalis or OVLT. Now you've probably heard before of something called the blood

brain barrier. This is a system of borders that prevent things that happen to be floating around in the blood from passing non selectively into the brain. So you know, the brain does need blood. It has to receive oxygen and other nutrients from blood flow, but the brain has to also protect itself against totally unregulated exchange with the blood.

And there may be multiple reasons for this, but one of the main ones I've seen is that this prevents blood borne pathogens from infecting brain tissue, so that seems important. So in regions where it's active, the blood brain barrier only allows selective passage of certain types of material from the blood into the neurons. But if you're part of the brain that needs to get raw data about the contents of the blood moment by moment, apparently it won't

do to be hiding behind this protective fence of cells. So, according to the authors here, the SFO and the OVLT, though they are in the brain, are located outside the blood brain carrier, so they can sort of taste the blood river unfiltered, undiluted to get a raw sense of

what's going on. To read directly from the paper here quote, it is thought that these SFO and OVLT neurons monitor the blood osmolality directly, possibly via stretch sensitive ion channels embedded in their plasma membranes that detect changes in cell volume following intracellular dehydration. However, the identity of the specific ion channel or other protein responsible for OSMO sensing by

these neurons is unknown. Furthermore, the possibility cannot be excluded that other cell types such as glia, play an important role in OSMO sensation. So here they identify, they put the flag up. For One more thing that hasn't fully been figured out in the science of thirst is what is the direct molecular mechanism that the neurons in these

brain regions use to detect changes in blood osmolality. Maybe these stretched sensitive cells that you get dehydrated and then send information based on that to the brain regions that then filter out to other brain regions from there, But we don't know for sure anyway that is sensing intracellular dehydration or increases in blood osmolality. But what about that other kind extracellular dehydration where the blood volume actually decreases overall,

such as after bleeding. Well. Decreases in blood volume are known as hypovolemia, like low volume hypovolemia, and they correspond with a decrease in blood pressure hypotension, and the body's reactions to hypotension take places sort of a complex chain of mechanisms involving multiple organs and several forms of a hormone,

very important hormone called angiotensin. You might see this abbreviated sometimes with like capital letters A in GI and then maybe A and GII for angiotensin one and angiotensin two. Apparently the most crucial form of the hormone is angiotensin two, which causes things like the narrowing of blood vessels. So if you shrink blood vessels and make them smaller, that helps keep blood pressure up when volume is low, and

it also leads to water reuptake by the kidneys. The kidneys are like holding fast to the water content rather than just squandering it as they might if you had

plenty of water in your body. And there's evidence that the presence of angiotensin two this hormone also causes a thirst drive to be generated in the brain, primarily involving the SFO or the subforonical organ Interestingly, in rodents, if you just give them straight angiotensin two, it causes what the authors call profound water consumption, just like voluminous drinking of water. But in humans, apparently, angiotensin two levels quote do not correlate well with the perception of thirst, and

infusions of physiologic levels of angiotensin two do not stimulate drinking. Interesting, so, perhaps while this hormone does things to increase blood pressure, like constrict blood vessels and cause water reuptake by the kidneys, it does not make us thirsty for water like it does in other animals for some reason, the authors write quote.

While this suggests that angiotensin two might be less important for regulation of drinking in humans, interpretation of these negative results is complicated by the fact that peripheral infusion of angiotensin two rapidly increases blood pressure, which can then feed back to counteract any effects of angiotensin two on thirst.

So maybe they're just complicated balancing interactions here that when you know if you directly infuse this hormone, it increases blood pressure, which has other downstream effects which which counteract the onset of thirst. Okay, I'm I guess just it just goes to show, you know, one of the factors of experiments with with with mice and other non human mammals is that we have a whole lot in common with them, but not everything is going to it's going to apply to us one to one, right, A lot does,

but not everything. Okay, But anyway, I guess what we're trying to figure out here is building a bridge from our existing knowledge about these brain regions that play a role in monitoring the body's osmolality and water content and u and regulate in these hormones that help regulate the body's physiologic response to dehydration, and how that connects to the actual behavior and the drives that we sense when

we get thirsty and go get water. Um so there there are sort of system wide homeostatic responses when when we get dehydrated again. The SFO and the OVLT, together with another region in between them, the median preoptic nucleus or MNPO. These three regions together comprise a hub called the lamina terminalys. This is sort of the brain's fluid control center. What is fairly well understood is the autonomic and neuroendocrine pathways by which the body responds to dehydration.

You know all these things we've been talking about. The angiotensin too, the constriction of blood vessels to increase blood pressure, water reuptake by the kidneys, the release of other hormones, not just angiotensin, but things like vasopressin and oxytocin. But what is less well understood are the mechanisms leading to the generation of thirst as a motivation state. But we

know some things that are very interesting. So to come back to something you actually mentioned earlier in the episode, Rob, the brain's regulation of water drinking is not based only on the current osmolality of the blood. So it's not just these brain regions that you dip a finger in and see how salty the soup is. The rain also appears to change our motivation to drink water before changes actually show up in the blood. Their behavior changes that

occur in anticipation of changes in osmolality. So what would this mean in plain English? Okay, so you're out in the hot sun, wrestling alligators, or you know, you're working up a sweat, whatever it is you're doing, and you come in, you get in the shade, and you drink a nice glass of water. When you do that, there is actually a delay on the order of tens of minutes. It might be ten, twenty or even more minutes before the water that you just drank is fully absorbed by

the digestive system and added into the blood. However, it might just take you a few seconds to drink a glass of water and then decide whether you're going to drink more. So, if it's taking your body tens of minutes to fully incorporate the water you've just consumed and for that to show up in a blood o molality test, how come you don't just keep drinking water constantly until

that happens. You know, you don't. Even if you're thirsty, you don't usually drink a glass of water and then just fill up another one, and another and another and another for you know, fifteen minutes or something. If your level of thirst were only based on your blood osmlality, you might do that. You might kill yourself just drinking gallons of water while you're waiting for your fluid monitoring

system to register the changes. Right, Yeah, yeah, I mean, I mean it needs to be Again, it comes back to just what a fine balance it is, and therefore you need you need different sensors in different places in the human mechanism here, right, So the sensation of your thirst being quenched by drinking water must be created by a different process altogether the author's right quote. Thirst is

not quenched by the reverse of the process that generates it. Instead, the brain appears to somehow detect the intake of liquid. It's usually thought that this happens somewhere in the oropharyans in the middle part of the throat, and then somehow adjusts the feeling of thirst in anticipation of the coming changes in blood osmolality. So it looks like what happens

is that you're dehydrated, you drink water. The swallowing of water is somehow sensed in the throat, and then these sensations are transmitted to the subformical organ, the sfo, and then from there they inhibit thirst generating pathways. And so this raises interesting questions how exactly do we sense water intake in the throat? This was not well understood at the time this paper was written. I actually have come across a couple of studies in the years since that

we can talk about as we go on. We might get more into those in the next part of the series. But at the time, some of the ideas out there were, well, maybe it has something to do with temperature. Apparently cooling of the throat triggers water intake signals, and evidence for this claim would be that research has found that cold liquids inhibit thirst faster than warm liquids. I haven't tried

it myself, but that sounds correct to me. Interesting and it would make sense water usually tends to cool the mouth in the throat, and that this cooling may be used as a rough signal that water is coming in. Also, it seems that cooling of the mouth on its own, even if it's not water, just making the mouth colder,

can somehow reduce thirst and reduce activity of the SFO. Interesting, so you would potentially be able to use just like a cooling breath of technique to inhibit thirst, possibly if you know, if the temperature explanation has anything going for it. But there may be other things as well. There may be other ways of sensing water in the oral cavity. Maybe some stuff more along the lines of what you

were talking about earlier. Things could have to do with taste sensors that somehow to detect the presence of water through acid sensing taste receptors or something, or there could be there may be some limited evidence that stretch receptors and osma sensors in the stomach might also detect water intake before full absorption. But again, at the time of this summary in twenty sixteen, this was just not fully understood.

I guess one way of looking at it would be that it's it's not necessarily like one trigger or one sensor that is that's playing a crucial role here. It's more of a whole suite of things that is that is generating this understanding of how much water has entered the system. Right. But whatever the exact mechanism is, it's definitely anticipatory in nature. It's definitely changing your behavior before the thing that your behavior is supposed to fix has

actually changed. Yet. Wow, Like, when you're done drinking the glass of water, you're still dehydrated. You're going to be

dehydrated for another ten to fifteen minutes at least. It's it's the kind of excellence in supply chain management that technology companies are chasing after, you know, the idea that they want to anticipate the need um and then you know, be able to h to alter the supply chain, you know, at moment to moment to make sure that the need is met without wasting water or product or whatever the case may be. Yeah, I like it. Okay, there's more

anticipation to come. How about anticipatory regulation of thirst from eating from food? Because when we eat food, thirst appears to be generated in anticipation of coming changes to blood osmolality. So why would eating food make us need water? Well, first of all, fluids are used in digestion. You think about when you eat food, you generate saliva you uh, you know, not to be gross, but there's a lot

of lubrication that needs to happen, Like swallowing requires some water. Oh, I mean you have to you have to chew up the food and form the bolus that will then travel down the throat. I mean, I think we've we've covered that on the show before. Like, think about it today your next meal. Really focus on everything that's going on in your mouth. It's a it's a beautiful chorus of disassembly and then reassembly into the right sort of package to then make the journey down to the stomach. It's

really it's like, it's beautiful and it's horrible. You can't think about it while you're eating, or at least I find I can't just think. I mean, have you ever thought of a more appetizing idea that you're like, mouth and throat are lubricating the ball of food that you're smashing up. Yeah, but anyway, so that's one thing. But then the other half of it is that eating usually increases blood os molality by adding salt and other things

to the body. Yes, yes, so much salt. So much so the body appears to have an anticipatory response to eating that is generated eating thirst before those changes even register. And this thirst that comes from eating is known as pran deal thirst. It seems to occur before changes in blood osmolality come into effect, so a lot of animals are observed to drink at the same time that they eat,

if they're able. The mechanism of this anticipatory neural pathway is still not fully understood, but if prandial thirst is not sated. I mentioned this earlier. Sometimes animal brains tend to react by reducing appetite until water is consumed. This is known as dehydration induced stanorexia. But in general, dehydration will cause animals to restrict their food intake, with some exceptions, of course, because some animals, you know, they get their

water entirely from food and so forth. But dehydration induce stanorexia tends to I thought this was interesting. Reduce meal size but not meal number, so it might not affect how often an animal is willing to eat, but how much they eat when they do eat, meaning that it probably works by causing an animal to terminate feeding behaviors earlier than they would normally each time it has a meal.

Now at the end of their rite. Up Here, the authors acknowledge that acknowledge some exceptions to the stuff they're talking about. These generalizations tend to be true for humans and rodents and some other animals, but of course they're very different ecological niches that will cause variation to these generalizations. For example, a lot of grazing herbivores do not seem to experience pran deal thirst or thirst related to eating. You know, because they eat all day, but they only

drink drink water a few times a day. And then they're very different kinds of animals like amphibians that don't technically drink at all, like many amphibians just absorb water through their skin. We've talked about amphibians before in the show and about how the you know, how delicate their place in the environment can be, and this is this is part of it. It's like if if if I'm in the environment, i am drinking it, I am breathing it, and my skin is the is the barrier through which

all this takes place. Yeah, very different relationship to one's environment, a very very different kind of chemistry of being for the for the amphibian, I recall it's been a while, but I recall reading a funny article about terrestrial toads that would primarily do water absorption through their pelvic regions, so they sort of like like thrust their lower bodies and bellies into any surface that's wet while they're while

they're hanging out in water absorption mode. All right, We're gonna ahead and close out this episode, but we will be back for a third thirst episode. We have a lot of additional information we want to get to. Don't worry there will be parasites in it, So it should be it should be a grotesque a good time. And of course, in the meantime, right in, let us know your thoughts on water. All of you are water drinkers.

You consume water one way or another or another, and I imagine you have some thoughts on all of this. Do you do you love drinking water? Do you hate drinking water? Is there? What are your thoughts on the consumption of cold water versus hot water or maybe prefer the lukewarm water? I mean, I guess they're factors we didn't even get into, you know, like sometimes cold water can be sensitive on the teeth and gums. The same can be said for hot water as well. So I

don't know. Perhaps you have thoughts on that. Have you never drunk water? You? Are you a creature that only absorbs water from chicken nuggets? Oh the chicken chicken nugget water? Yes? Well, anyway, right and let us know it's all fair game. In the meantime as usual, Core episodes of Stuff to Blow Your Mind Tuesdays and Thursdays and the Stuff to Blow Your Mind Podcast feed. We have a listener meant on Monday, Artifact on Wednesday, and on Friday we do Weird House Cinema.

That's our time. Just had most serious matters aside and just talk about a strange film. Huge thanks, as always to our excellent audio producer Seth Nicholas Johnson. If you would like to get in touch with us with feedback on this episode or any other, to suggest a topic for the future, or just to say hello, you can email us at contact at stuff to Blow your Mind dot com. Stuff to Blow Your Mind is production of iHeartRadio.

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