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00:01 | All right, y'all, you guys a good day. Yeah, it's |
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00:06 | be raining on Thursday. I think heads up because I know you guys |
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00:10 | to know about these types of All right. Um I made a |
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00:16 | . Um I don't know if you the promise, but I said today |
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00:18 | the most difficult day in terms of rest of the semester. Um And |
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00:22 | not doing that again to scare I'm just trying to kind of perk |
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00:25 | up to say, all right, a part where I'm gonna need to |
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00:28 | attention and I'll point out was I'll say this is the time. |
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00:32 | ? Right now, this is not time this actually uh this part of |
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00:35 | lecture is actually pretty straightforward and we describing how a kidney goes through the |
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00:41 | of filtration. We were looking at Nephron and we said, hey, |
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00:44 | plasma is flowing into the glomerulus, glomeruli uh fluid is being pushed out |
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00:50 | a series of pressure, right? Those pressures collectively are referred to as |
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00:54 | net filtration pressure that drives fluid into tubular portion. And now we have |
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00:59 | fluid, which is more than more than we are trying to get |
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01:02 | of. And so we need to modify it. And what we call |
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01:06 | filtrated fluid is just the filtrate. right, it's not urine yet. |
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01:10 | won't be urine until the end of class. Ok. So what we're |
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01:14 | do next is we're going to reabsorb materials, the body wants to keep |
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01:20 | the body. All right. So gotta think about it like this, |
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01:23 | tubule is outside the body and we're to move things from outside the body |
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01:28 | into the body, right? And that's what that first step is |
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01:32 | Now, this is very, very . We're only gonna take in those |
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01:36 | that we want to keep most of takes place in the proximal convoluted |
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01:43 | So whenever we're talking about this we're just, we're just sitting up |
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01:46 | at that front end. All Um We've already mentioned we're trying to |
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01:50 | the things that we want. So statement I have a high reabsorptive capacities |
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01:54 | the substances the body needs. That's I'm saying is if your body |
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01:58 | it's going to keep it and anything your body doesn't want is just going |
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02:01 | allow it to keep on flowing with filtrate. Remember what the filtrate |
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02:06 | It is plasma minus the plasma right? So even though we give |
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02:11 | a special name, it's not that different than what we've already started |
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02:15 | All right. Um And so there's processes that we're gonna be looking at |
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02:19 | or, or generally not looking but just generally that are taking place |
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02:23 | that we have cells. And so have to add the pass through the |
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02:26 | or have to pass between the So we're gonna take advantage of either |
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02:30 | those two simple processes. I know seems stupid that I say that. |
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02:34 | . All right. So what are gonna do is we're gonna pass through |
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02:36 | cells or we're gonna pass in between cells. And so everything is gonna |
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02:40 | dependent upon the permeability of those cells particular substances. And this is where |
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02:46 | fall back on something we learned a time ago. You're like crap. |
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02:51 | hope I didn't have to something I forgotten. This is actually pretty |
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02:56 | Wherever sodium goes water follows, you that wherever water goes, everything else |
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03:03 | . Taking into consideration osmotic uh ideals osmotic characteristics. All right. So |
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03:09 | know that you know the rest of story of perme or the of this |
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03:13 | of reabsorption. All right. if everything starts with sodium, we |
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03:18 | need to know what sodium is OK. So in the first |
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03:22 | sodium, 70% of the sodium or as it says, about two thirds |
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03:27 | the sodium in the uh filtrate is to be reabsorbed through the uh proximal |
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03:34 | tubule. All right. And this the stuff that we care about. |
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03:38 | . This is where we say when the reabsorption is taking place at the |
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03:41 | end over here in the pro this why. So it plays a pivotal |
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03:44 | in the reabsorption of water, reabsorption glucose, reabsorption of amino acid reabsorption |
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03:49 | just you name it. It's It's being reabsorbed. It starts with |
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03:54 | because wherever sodium goes, water follows wherever water goes, other things follow |
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04:00 | with it. All right. 25% of the sodium is gonna be |
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04:05 | in the loop of Henley. All . Now, we're gonna, this |
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04:08 | part of the thing that's gonna make , the that section if I say |
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04:11 | difficult thing, this is part of role. And so what we're gonna |
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04:15 | is we're gonna use this sodium to create an environment so that our bodies |
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04:21 | create urine's ovarian concentrations. So we're describe that later. But that's the |
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04:27 | why is because of the way that is being reabsorbed in the loop of |
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04:31 | . The third place is the stuff your grandma cares about. Not you |
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04:35 | much because, well, you're young you don't care about salt intake. |
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04:39 | you know, grandma, she sits and looks at that salt and wonders |
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04:42 | or not I'm gonna put it in food, right? And the reason |
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04:45 | that is because sodium load becomes important is measured and it's in the distal |
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04:51 | tubule where it has a key role ensuring the proper extracellular fluid volume. |
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04:58 | other words, blood pressure is dependent salt. I'm gonna put that in |
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05:02 | because it's not really true. It's true. All right. But the |
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05:07 | of salt in the sodium reabsorption allows to bring water back into the body |
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05:11 | this particular place. And it's what regulate to make sure water, our |
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05:15 | salt balance is correct. All So your blood pressure and all the |
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05:20 | pressure meds that everyone takes is focusing . All right. So three different |
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05:26 | , three different rolls of sodium and are the key, the key |
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05:32 | So let's look at the proximal convoluted . All right. So on the |
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05:39 | side, so the Luminal side is the tube. This is where you're |
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05:42 | see sodium channels, sodium glucose sodium exchangers. All right. So |
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05:49 | in all three of these cases, am I doing? I'm moving sodium |
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05:53 | its concentration gradient into the cell. this is a trans cellular transport. |
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05:58 | right. Now, granted there is uh secondary active transport that's taking |
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06:03 | but it's with the other materials, glucose and the amino acids. So |
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06:06 | not really talking about them right So sodium goes into the cell and |
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06:10 | I put sodium in the cell to sure that there is still flow into |
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06:13 | cell, I need something to pump out of the cell. And so |
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06:17 | the interstitial fluid side, I'm going have sodium potassium pumps. So what |
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06:21 | doing is I'm allow sowing sodium which a higher concentration in the tubule than |
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06:25 | the cell to move into the I pump it out. And so |
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06:28 | creates a constant flow of sodium back the body. So far. So |
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06:33 | , pretty straightforward, right, So sodium gets moved into the |
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06:40 | moves to the other side of the into the interstitial fluid. So water |
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06:44 | attracted to the sodium. So water now, where is water going to |
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06:48 | ? Well, it can go through cells. We have aquaporin in |
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06:51 | Aquaporin can be found throughout the, Nephron. We have aquaporin that are |
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06:57 | open in the proximal convoluted tubules. water always follow sodium in the proximal |
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07:01 | tubules. But when we get to distal end, so when you get |
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07:04 | to the distal tubules, you get to the collecting ducts, you get |
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07:07 | to the collecting tubules, the aqua are gonna be introduced at specific times |
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07:13 | that you what you say is that exist in a closed state so I |
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07:17 | open and close them based upon All right. So I'm gonna move |
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07:24 | in when my body needs water further . But over the approximal co theta |
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07:31 | water follows sodium easy peasy. All . There's also tight junctions that aren't |
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07:37 | tight junctions, they're leaky. So leaks in between the cells as |
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07:42 | Again, following salt. Now, you went back and tried to remember |
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07:48 | the little tiny, stupid little anecdotes tried to make. I said sodium |
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07:52 | water are like the cool kids at . And we said chlorine was like |
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07:57 | , the guy in the friend right? So chlorine is gonna go |
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08:02 | sodium goes, right? It's attracted to sodium. So it's going to |
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08:08 | chlorine. So that's an easy thing do passive. You don't need any |
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08:15 | to do. So just follows it as electrical gradient, potassium, potassium |
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08:21 | gonna follow water because water is now an osmotic gradient. There's less or |
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08:27 | more potassium now than in the interstitial . So potassium is gonna move into |
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08:31 | cells. Now. Uh this is be done through paracellular rather than through |
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08:35 | cellular mechanisms. When you get into nephronic loop, there's some uh res |
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08:40 | there as well. Well, we're ignore that for right now. And |
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08:43 | ultimately, when we get to the tubules, uh we're going to reabsorb |
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08:47 | potassium. Actually, what we're doing we're doing an exchange here is potassium |
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08:52 | protons and these are gonna be done the type a intercalated cells. So |
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08:56 | absorb potassium and I give up a . And what do we say type |
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09:02 | intercalated cells? What were they responsible acid secretion? So that's what really |
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09:07 | the exchange is there. So that's you get rid of the extra protons |
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09:10 | of your body. So, so as anything weird sodium goes in. |
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09:15 | water goes in. So chlorine goes . So potassium goes in. So |
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09:21 | goes in. Where's glucose going? , it's moving along with the sodium |
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09:26 | again being pumped the other direction so . Does it sound like things that |
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09:30 | body wants? Does your body want ? Did you stand in line at |
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09:35 | long time at the chick fil A here to get your glucose? |
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09:40 | Yeah. Uh huh I didn't even she, you're eating your chick fil |
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09:43 | . So how long would we How long a wait was that was |
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09:45 | 30 minutes? 30 F-15 man. a long time to wait for good |
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09:54 | . Then your amino acids, your acids are gonna do the same thing |
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09:57 | got these co transporters. So sodium in amino acids going in, they're |
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10:02 | the osmotic gradient as well. And we get to the weird one, |
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10:06 | old urea, nitrogenous waste in Uh If you're not aware of |
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10:11 | we don't just produce uh urea, actually produce a whole bunch of different |
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10:16 | . So you have urea that's from breakdown, uric acid that's from nucleic |
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10:19 | breakdown, creatinine, that's from creatine . So you're, you're producing different |
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10:25 | of nitrogenous waste. And so uh of those are being produced, they |
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10:30 | have to, uh, leave the . Um, and actually we're really |
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10:34 | when it comes to uric acid. , and I'm not gonna go into |
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10:37 | , but that's uric acid is the that leads to gout when we can't |
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10:41 | uric acid properly. Um, that's gout is, but we're more interested |
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10:46 | urea because that's the primary form of waste. All right. So, |
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10:52 | what we said about Yuria, urea slow. They're like your slow |
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10:57 | Actually, I don't know if I've explained Uria to you. Have I |
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11:00 | I, OK. So you're like slow friend. They, they, |
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11:02 | still follow along. It's, it's of the crowd, right? It's |
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11:06 | the fringes. It's cruising along with , but it's a lot slower. |
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11:09 | , it's the dumb jock friend, know, I mean, again, |
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11:12 | got to think of the stereotypes and he the, the what? You |
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11:16 | , whatever. All right. So follows along but it does so |
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11:22 | It doesn't, it doesn't reabsorb at same rate. And what ends up |
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11:26 | is, is that in the proximal tubule, you reabsorb about half of |
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11:30 | Urea that's located in the filtrate. then when you get down to the |
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11:34 | of Henley, then the loop of says, no. Uh II I |
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11:37 | you back in the body. So starts pumping it back out and so |
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11:41 | get rid of it all and then slowly moves back in, when you |
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11:44 | to that distal end of the So down in the collecting tubes. |
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11:48 | so what ends up happening is instead getting rid of all the urea that |
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11:51 | body is producing, you maintain a amount of urea in your body. |
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11:58 | in particular, that urea becomes really important because it's gonna play a |
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12:02 | along with the sodium to help maintain create that osmotic gradient that I keep |
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12:10 | to. OK. So it's there a reason. It's not just, |
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12:16 | , we can't get rid of it we just live our lives. All |
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12:20 | . So how many slides was Like 12, something like that? |
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12:26 | don't know. 10. All And so that took us 12 minutes |
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12:30 | go through. You already know how Nephron works. Wherever sodium goes, |
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12:35 | follows wherever water goes, all the things follow. And it's as simple |
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12:41 | that. Anyone who teaches you they're just trying to make it scary |
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12:46 | , and hard. OK. So the first part. So we |
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12:52 | we have all this stuff that we wanna keep, but it's stuck |
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12:56 | So we move it out through that of reabsorption. We start off with |
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13:00 | um what was, what did we ? It was 100 and 20 |
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13:03 | 100 and 20 mil. And so we're doing is we've removed roughly 19 |
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13:08 | , 100 and 19 mils back into body of water and all these salts |
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13:12 | glucose and amino acids. All But there are things in your body |
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13:19 | either can't be filtered or are not efficiently. And so there are things |
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13:24 | want to get rid of. All , you guys have heard about the |
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13:28 | of consuming poppy seeds, right. . If you go have a poppy |
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13:33 | bagel, are you supposed to go a drug test that week? That |
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13:37 | ? No. All right, because down the poppy seed results in a |
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13:44 | signal for opiates because poppy seeds are seeds of the poppy plant, which |
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13:48 | where you get the materials for It's basically an opiate. All |
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13:53 | So what this is, is a that's telling your body is metabolizing |
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13:59 | And so you have toxins in your and sometimes you can only get rid |
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14:03 | the toxins at a very specific In other words, at the rate |
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14:06 | filtration, but some toxins, you want to get rid of a lot |
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14:11 | . And that's what the third process . Is this process of secretion. |
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14:16 | right here, what we're doing is doing a type of trans cellular |
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14:20 | It needs to be active because what are doing is we are grabbing things |
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14:24 | saying I am pumping you into the . So we're going from the blood |
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14:29 | the tubule, we're not filtering, is blood that has gone through the |
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14:33 | process is now moving through the peritubular . All right. And what does |
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14:39 | mean again next to the tubule? . So these are uh capillaries that |
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14:45 | right next to the tubule. And you have machinery carriers that are literally |
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14:50 | of binding certain molecules and moving them and across the tubular surface into the |
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14:59 | . Now, two things that are , really simple is the potassium and |
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15:03 | protons. All right. So proton is gonna occur along the entire length |
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15:08 | it's gonna be dependent upon your acidity the body body. The more protein |
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15:12 | eat, the greater acidity your blood . All right. Vegetarians have less |
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15:18 | blood, meat eaters have more acidic . It's just a function of eating |
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15:22 | or proteins. All right. So that happens, the body says uh |
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15:27 | I don't like that. So, I need to do is I need |
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15:29 | get rid of those protons. And this is what you're using is using |
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15:33 | mechanism to get rid of the right? Intercalated cells in particular are |
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15:39 | for get getting rid of those protons exchange for reabsorbing potassium. But what |
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15:44 | it say? It says across the length? I'm gonna go ahead and |
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15:47 | . I'm trying to get rid of because I'm trying to maintain a very |
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15:51 | blood. What about potassium? in the proximal convoluted tubule, we |
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15:58 | abs reabsorbing the potassium, right? followed the water, it's in the |
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16:03 | convoluted tubule where you're seeing potassium All right. And here what we're |
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16:09 | is we're trying to maintain the appropriate concentrations. All right. Now, |
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16:15 | me ask you a question. If were uh uh potassium deficient. What |
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16:19 | you gonna go do? Eat a ? Actually, it turns out bananas |
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16:23 | as potassium rich as we think they . But that's what we all |
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16:26 | That's what they told us. So what we're gonna do, right? |
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16:29 | so you can imagine, I'm just when I'm uh potassium deficient, one |
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16:33 | the things I I know to do go eat my bananas. But one |
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16:37 | the things your body is doing is , oh, instead of it going |
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16:40 | and peeing it out, I'm gonna ahead and pull it back from the |
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16:42 | . That's what it's trying to do it's doing it at the level of |
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16:45 | convoluted tubule. All right. I know why this isn't advancing, but |
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16:50 | we go. All right. So concentration is high in the plasma. |
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17:00 | what it's gonna do is it's gonna into interstitial fluid and from the interstitial |
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17:04 | , it's gonna be pumped by the potassium pump. All right. So |
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17:10 | , that's what we're dealing with here in the distal convoluted tubule. All |
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17:15 | . So what we're gonna do is going to exchange it. So the |
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17:18 | that you should be looking for is here, right? So, if |
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17:20 | get high potassium, right? What's happen is is I am going to |
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17:26 | it into the tubular cells, So this is secretion. Look which |
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17:30 | I'm going, I'm going out of body out into the tubule so that |
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17:34 | can be secreted. So I pump into the tubular cell and then it |
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17:39 | through its potassium channel and out it goodbye. Good rhythms. All |
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17:44 | And what do I exchange for Well, I have exchangers as |
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17:49 | Actually, that's not right. Oh saying, yeah. So here is |
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17:55 | exchange is taking place paracellular. But me point this out and make it |
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18:00 | , really crystal clear. The thing becomes really important about this. The |
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18:06 | that I use to determine when I potassium out of the body is dependent |
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18:13 | the hormone aldosterone. All right, is what aldosterone does when I am |
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18:22 | low in water or basically my blood decreases. Or if my potassium levels |
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18:28 | , what's gonna happen is that results a production of aldosterone from the adrenal |
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18:33 | that aldosterone acts on the de the principal cells in the distal convoluted tubule |
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18:38 | causes them to do two things. , increased number of sodium potassium |
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18:44 | When I do that, I'm gonna pumping potassium out of the body. |
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18:48 | also doing what in the name sodium pump and potassium potassium out of the |
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18:57 | . So what am I doing? coming in? And where sodium |
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19:01 | water follows. So that's gonna be blood pressure. All right, that's |
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19:06 | idea is what it's doing there. if I just pump potassium into those |
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19:10 | cells, it still needs to have way to get out of the tubular |
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19:13 | . And so this is causing those cells, those tubular cells to introduce |
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19:18 | potassium channels. So the potassium can flow on out. So, aldosterone |
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19:22 | the hormone that's being produced to allow to secrete the potassium. But you |
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19:29 | it also as a secondary role, we'll get to it. I've already |
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19:32 | told you, it allows me to sodium into the body. And if |
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19:35 | pump sodium into the body, I water in the body. If I |
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19:38 | water in the body, I raise blood pressure. So aldosterone has a |
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19:42 | role allows me to secrete the It allows me to increase blood |
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19:49 | Ok. Yes, sir. By it's sorry, it should be a |
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20:01 | amount of potassium in the body, ? So the idea is I'm trying |
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20:05 | get rid of potassium. I wanna it. It's not, I'm not |
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20:09 | low. That's I I'm backwards. my apologies. Good catch gold |
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20:17 | I don't pass out gold stars every . I should though. But there's |
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20:23 | else that you put in your body I already mentioned it. I said |
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20:25 | the poppy seeds, right? Uh day, all day long, you're |
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20:30 | materials and you are building up toxins your body, right? And so |
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20:34 | body wants to get rid of So, um let's do it this |
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20:41 | . We'll see how, how knowledgeable are on your drugs. How often |
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20:45 | you allowed to take an Ibuprofen every hours? How often are you allowed |
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20:52 | take acetaminophen? Four hours? How an Aleve 10 man? Why do |
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21:04 | know all these things? Doctor Because I have four kids and you |
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21:06 | to manage fevers sometimes. All Why do they all have different |
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21:13 | I mean, they all do the thing, right? I mean, |
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21:16 | mean, some are in a, are not some working the liver, |
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21:19 | are processed through the kidney. But , why, why do they all |
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21:22 | different times? What do you think , what half life? Ok. |
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21:31 | yes, that's what I'm looking for basically they're metabolized differently and so they |
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21:35 | metabolites at a specific rate. And there's another half which we'll get to |
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21:39 | a second, which is their plasma . All right. But in |
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21:42 | you break them down and if you them down faster than you can get |
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21:45 | of them, those toxins will build and cause all sorts of horrible problems |
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21:49 | you, right? So this is . You can do the same thing |
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21:54 | vitamin C, right? You notice , have you ever, do you |
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21:58 | eat vitamin C? Do you take C. So when I was, |
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22:02 | I was just like, y'all's you know, you go down to |
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22:04 | GNC and you'd get like a big of the, the orange flavored, |
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22:09 | know, vitamin C and it's oh, I don't know, sweet |
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22:12 | , you know, just start popping . All right. But if you |
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22:15 | read the back, it's like, is the maximum amount you can take |
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22:18 | a day? You guys know 3000 after 3000 mg, you're starting to |
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22:25 | into toxic doses of vitamin C. ? Yeah, don't, don't do |
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22:30 | . That's bad. It starts destroying . All right. But basically you |
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22:34 | , there's a certain rate at which can get rid of the vitamin |
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22:37 | All right. Now, the process filtration is a fixed rate. |
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22:44 | So that's what we talked about the , right? The glome filtration |
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22:48 | it sits more or less at at a constant rate depending on what |
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22:52 | doing. I mean, if you're up sitting down, it makes small |
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22:55 | to maintain within a certain range. so the fluid that happens to be |
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23:01 | the materials that happen to be in filtrate at the time are gonna be |
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23:04 | at that rate, right? But I have something I need to get |
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23:08 | of, I'm gonna use this method secretion so I can get rid of |
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23:13 | faster. All right. So this why we end up with like poppy |
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23:18 | and stuff in our body or not seeds, but the the stuff. |
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23:21 | so what we have is we have incredibly unique system that is highly |
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23:26 | And beyond what we're going to talk here in the class because there is |
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23:29 | one molecule, there are hundreds of specialized carriers that recognize anionic metabolites and |
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23:38 | capable of binding them, grabbing on them and then moving them over into |
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23:43 | filtrate. This is what some of look like. Ok. That's what |
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23:48 | trying to show you these molecules that listed down there. Actually, I |
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23:52 | anions, it looks like I was . It's C ions, my my |
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23:55 | . All right. So what this is you're no longer dependent upon the |
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24:03 | rate to get rid of the Your body is looking for ways or |
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24:07 | discovered ways to get rid of toxins a faster rate than normally would occur |
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24:14 | of this process of secretion. So not just potassium and it's not just |
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24:21 | , it's metabolites of things that we . All right, whether it be |
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24:26 | we eat or drug we take, it's a hormone that we're breaking |
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24:33 | This is what this mechanism allows us do and it hastens the rate of |
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24:40 | so that their toxic levels do not . Ok. So, so |
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24:47 | so good. So the process that nephron goes through three steps, first |
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24:54 | is filtration discriminate, non discriminate, discriminate, just pressure is just |
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25:06 | it's bulk flow, absorb or Discriminate, non discriminate, discriminate, |
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25:13 | picking, picking the winners and the . And then finally, secretion, |
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25:18 | , non discriminate, discriminate, it's which things are going. If you |
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25:25 | have the right channel, the right to pick up the thing, then |
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25:29 | thing is stuck in the blood and follows all the rules. I |
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25:33 | all this, you know, the example I used, I used to |
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25:37 | and I apparently I just confused everybody no one really learns the law of |
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25:41 | law of mass averages or law of action as well as they should. |
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25:47 | you can imagine in circulation, let's you have um four molecules, I'm |
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25:53 | stay with simple numbers, right? let's say you filter two, |
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25:58 | But let's say that those are free . Let's say you have also four |
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26:02 | bound up, right? And I to get rid of more of those |
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26:06 | . The way that I can get molecules unbound is by removing them from |
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26:11 | environment, right? The the the ones. Did you guys learn that |
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26:15 | one point a long time ago in ? Two, maybe, maybe |
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26:20 | you learn that this idea of free bound molecules. OK. Um When |
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26:25 | saw the furrowed brow that scared me a moment, but then it was |
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26:27 | , oh yeah, yeah. All right. So one of the |
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26:30 | that we're doing here is we're forcing out of the system faster because you're |
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26:36 | with the ratios of free to bound . Because if I'm moving, if |
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26:41 | removing bound molecule or free molecules that means they're getting unbound quicker, |
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26:46 | I can pick them up faster if makes sense. But if that confuse |
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26:51 | don't worry about it. Just understand is a mechanism of quicker removal. |
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26:59 | , are you with me? Three ? Yes, sir. Almost. |
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27:08 | quite well. Maybe. Now I think about pocket M and MS and |
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27:16 | this is true, well, so Pocket M and MS, those |
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27:21 | be like your bounds. Can't, eat a pocket M and M until |
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27:25 | becomes a hand. M and you're gonna remember that till the day |
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27:30 | die. You know that right? gonna be 40 years old and you're |
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27:33 | explain to your kids in a biology . All right. This I think |
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27:37 | understand. M and MS and All right. Are you ready to |
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27:46 | on to something different? How many you have ever peed in a |
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27:52 | Everyone better raise their hand. If been to a doctor, you peed |
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27:56 | in a cup. And what are doing? They ask you to pee |
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27:58 | the cup. They put you put on the tray with your name on |
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28:01 | , right? Have you ever do ? And then they go take your |
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28:06 | why are they doing this? What they checking on? No, unless |
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28:12 | a drug test. All right, doesn't care if you're on drugs, |
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28:16 | you're lying to him. In which he needs to know or she needs |
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28:18 | know. So that whatever they're prescribing you is not contraindicated. What |
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28:23 | doing is they're checking your GFR. , typically they don't need to do |
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28:28 | specific test that we're about to But usually what they're doing is they're |
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28:32 | at your creatinine levels and they look your creatinine levels in the blood and |
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28:36 | creatinine levels in your urine. And they measure your GFR based on that |
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28:40 | GFR being your glomerular filtration rate, ? And your GFR is an indicator |
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28:46 | kidney function. If your GFR is relative to the average, that means |
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28:50 | kidney is not working appropriately. So one of the things that they're always |
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28:55 | when you go to the doctor, check your blood pressure with the little |
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28:58 | single mammon meter. See I got off without thinking about it right. |
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29:04 | check your blood ox with the little oximeter, right? And then they |
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29:10 | go pee in a jar or pee a cup and then set it on |
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29:13 | tray and then a couple days you can log in and you can |
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29:16 | your numbers right. And they're looking your, you know, your GFR |
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29:21 | that relative to your blood. the proper way to measure GFR through |
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29:27 | function is making sure, you know much stuff is actually there because they're |
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29:32 | creatinine production is constant and it's I mean, if you work out |
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29:38 | frequently you're gonna make more creatinine. ? If you're a lump on the |
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29:42 | , you're gonna make less creatinine. ? So, it's, it's |
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29:45 | it's a very complex form. You actually go look it up on |
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29:49 | They actually show you it's different for Americans than it is for, |
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29:53 | uh Western Europeans. And they have formulas for everybody. You know, |
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29:58 | , it's a load of fun, ? But what you can do is |
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30:02 | pump somebody full of inulin, not pump, people full of insulin. |
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30:07 | things happen. All right. So pump them full of inulin. What |
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30:11 | inulin? Anyone's gonna quickly Google that boy. You don't have to. |
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30:16 | were you inulin is a molecule that's in uh plants and it is a |
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30:25 | that can be filtered through the filtration of the Nephron. So it's actually |
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30:31 | small, even though if you look up, it looks really big and |
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30:34 | , I think it's based, it's type of sugar if I remember. |
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30:37 | . I can't, I'm not 100% , but it can't be filtered or |
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30:42 | , it's filtered, but it can't reabsorbed and it can't be secreted. |
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30:47 | if you go and measure, you , if you put in a uh |
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30:50 | certain amount and then they go peak little bit later, you can |
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30:54 | and then you go take the you can measure the inulin in the |
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30:56 | . You can measure the inulin in urine. And then using those two |
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31:00 | , you can then determine whether or your kidney is functioning by filtering |
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31:05 | that, that inulin at a constant at a specific rate. So that's |
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31:09 | they're doing here. And I'm gonna to bet that 100% of you have |
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31:14 | had to be injected by it with because it's not something they do that |
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31:19 | anymore. Now, it's all about formula. All right. But that's |
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31:22 | best way to do it because you , you're putting in a constant amount |
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31:25 | a finite amount or a fixed amount then you can measure it. And |
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31:29 | you can use a formula like this a time course to see. All |
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31:34 | , is this right? So, my concentration of urine of the |
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31:37 | uh what is the volume of urine I'm collecting? Divided by the concentration |
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31:40 | the inulin in the plasma that will you your GFR, I'm not gonna |
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31:44 | you that formula. I'm just saying , it's a simple thing that you |
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31:46 | measure right? Because it's being And what this is an indicator of |
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31:52 | your ability of your kidney to filter specific amount of plasma from or of |
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32:00 | substance. This is what plasma clearance . And I'm gonna, I gotta |
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32:03 | the definition out loud because if I it wrong, I'm gonna screw it |
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32:06 | for all of you. OK. clearance is simply the volume of plasma |
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32:13 | of a particular substance per minute. it's not like, oh I cleared |
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32:19 | a couple milligrams of the substance. saying the volume of plasma. So |
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32:26 | what you're measuring is the volume of having been cleared over that period of |
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32:32 | per minute. All right, different have different plasma clearances. Going back |
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32:41 | the example, we used Ibuprofen, . I don't know what a leave |
|
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32:48 | . I never bothered learning, but substance they're all cleared at different |
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32:54 | And so if you took Ibuprofen every hours, because you're not clearing it |
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33:01 | enough, Ibuprofen would build up cause if you are taking acetaminophen, |
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33:09 | Actually, we found out it was more toxic than we realized. You |
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33:13 | that about f four or five years when they're like, everyone stopped taking |
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33:17 | and everyone stopped taking acetaminophen. They , it's there's a certain threshold at |
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33:22 | point it becomes highly, highly So it's, you know, but |
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33:26 | it's like every four hours, you clear out a dose of acetaminophen of |
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33:31 | is it? 500 mg, I , or maybe 1000 mg, you |
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33:35 | clear that out in four hours. if you take 4000 mg, you're |
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33:40 | your luck. So what this really is it demonstrates like, hey, |
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33:46 | , different drugs, do different So I need to be careful what |
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33:49 | take and when I take it you suffer from horrible, horrible head |
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33:55 | not migraines, just headaches or you can count but taking acetaminophen or |
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34:01 | doesn't do any good. Does Yeah. Um, but like if |
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34:05 | have kids, I'm, I'm gonna , I'm gonna use this example. |
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34:08 | works for headaches too. I'm gonna you something here. I am not |
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34:13 | medical doctor. All right, I'm to information I received from my medical |
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34:20 | and all the nurses we worked with we had, we're dealing with our |
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34:23 | and when they were sick. All . And they say, look, |
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34:27 | you have a high temperature or give them a, one of the |
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|
34:31 | , acetaminophen or Ibuprofen. All Now we said Ibuprofen is every six |
|
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34:36 | . So the next time you can Ibuprofen would be six hours later, |
|
|
34:39 | ? But if you've ever had a baby at two o'clock in the |
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34:42 | you're desperate to get them to be , right? And sometimes bourbon is |
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|
34:47 | the best solution. I've got three to laugh at that one. All |
|
|
34:55 | . So what do you do? have a fever, you gotta put |
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34:59 | down, you gotta get them So what do you give them? |
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35:02 | you go ahead? It's like four later. Do you go ahead and |
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35:04 | them the Ibuprofen? Yeah, you give them at the three hour |
|
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35:09 | you can give them the acetaminophen and at the six hour mark, you |
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35:14 | give him the Ibuprofen and then three later, you can give them the |
|
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35:17 | and then you can give the So if you're struggling with like a |
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35:21 | headache that won't go away, you do the same thing to yourself because |
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|
35:24 | allowing the drug to clear based on plasma clearance, right? Acetaminophen, |
|
|
35:31 | actually have that wider swath. But also giving a medication in this particular |
|
|
35:37 | , the NSAID to deal with the without interfering or losing the the other |
|
|
35:45 | . And just so that, you Ibuprofen, like I said, that's |
|
|
35:48 | through the kidney acetaminophen is processed through liver. So you're affecting two different |
|
|
35:53 | . You're not killing both things at same time. So plain appearance is |
|
|
36:02 | because it tells you how quickly you get rid of a substance. All |
|
|
36:07 | , and all these things. go ahead. No. So this |
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|
36:14 | solely how quickly it lo the that unit of blood loses that substance over |
|
|
36:20 | , right? So notice it doesn't with, you know, can I |
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|
36:23 | the material or you know, what the rate of metabolism? It's simply |
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|
36:27 | rate at which you are clearing it the blood. Yeah, say |
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|
36:34 | do they have a chance to. they wouldn't, they, since they're |
|
|
36:39 | roughly the same thing, they're not competing. But what they're doing is |
|
|
36:42 | overlapping the, the functionality of that . So, the effect is so |
|
|
36:47 | the effect, more or less stays over time, at least with the |
|
|
36:50 | of the ibuprofen and the acetaminophen. . So that would be, the |
|
|
36:54 | is like, oh, man, got this, you know, toddler |
|
|
36:58 | at the top, top, top their lungs, their fever has come |
|
|
37:01 | . What do I do? You , I can deal with it and |
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37:04 | not gonna poison them, which is really important thing when you're a parent |
|
|
37:07 | poison your Children. That's, that's bad thing just in case you didn't |
|
|
37:12 | . So this is a little chart kind of shows you plasma clearance so |
|
|
37:16 | you can visually see this. All . So this would have been inulin |
|
|
37:20 | here, right? So you get but you get no reabsorption, you |
|
|
37:24 | no secretion. And so what you say is that the plasma clearance rate |
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|
37:29 | a substance that is only f but re reabsorbed or secreted is the same |
|
|
37:34 | the GFR Du. That makes right? If it's only being |
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|
37:39 | it's got to be the plasma clearance gonna be at the rate at which |
|
|
37:42 | filtered. All right. But we some substances that will be filtered and |
|
|
37:47 | reabsorbed, but they're not secreted. typically what we'd say is that their |
|
|
37:51 | clearance rate is less than G the again, that makes sense. So |
|
|
37:56 | filtering it, I'm returning it back the body, you know. So |
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|
38:00 | of them are gonna be returned some of them are gonna be returned |
|
|
38:03 | partially. But as the end result if I go check the urine, |
|
|
38:08 | gonna have less than what was So that makes sense. All |
|
|
38:12 | So an example of complete would be , right? We work really hard |
|
|
38:17 | that glucose. So put it back the body urea. We already said |
|
|
38:21 | just slow. So that's why we up with half of the urea that |
|
|
38:25 | uh filtered is um gonna be secreted excreted. Um The last one is |
|
|
38:31 | where we have a substance that is and secreted but not reabsorbed. Then |
|
|
38:35 | filtration rate is greater than the All right. So many of the |
|
|
38:40 | protons in your body, that rate removal is far greater than just filtration |
|
|
38:46 | . So, that was what I trying to get to so far. |
|
|
38:51 | good. All right. OK. here, easy subs or easy structure |
|
|
38:58 | now. Ok. Bladders. What's purpose of the bladder to store urine |
|
|
39:05 | that we don't make messes everywhere we . No one thought that was |
|
|
39:13 | Are we not a potty humor No, no potty humor, maybe |
|
|
39:18 | little bit. Ok. All We're making about a mil per minute |
|
|
39:23 | urine. Right. So, right , as I'm talking, I've been |
|
|
39:28 | for 40 minutes. You've made 40 of urine each. You're a pea |
|
|
39:34 | class. Anyone making puddles, you have to tell us if you |
|
|
39:44 | Yeah, I thought we were friends here, you know, I |
|
|
39:47 | you never know. We, So what do we do? We |
|
|
39:50 | wait. Right. And then when appropriate, I mean, when we're |
|
|
39:55 | the age of two, we just of went whenever, but when it's |
|
|
39:59 | , we find our way to the and then we use the restroom to |
|
|
40:03 | rid of the the urine that was and stored in the bladder. So |
|
|
40:07 | purpose of the bladder is simply that store the urine until maturation. There |
|
|
40:11 | a couple of layers. The outer is referred to as the mucosa or |
|
|
40:15 | . This is the inner going inner outer. So mucosa is the inner |
|
|
40:19 | . It's basically a unique type of cell. These are called transitional epithelial |
|
|
40:24 | . Um it takes real time and to learn how to identify them under |
|
|
40:28 | microscope because they change shape. What do is they kind of look roundish |
|
|
40:34 | you have an empty bladder. But the lad bladder expands the cells themselves |
|
|
40:38 | out and flatten out. So they like a um uh like a squamous |
|
|
40:44 | cell. Um And I know that's helpful because you've all taken histology, |
|
|
40:49 | ? I'm just un teasing. I none of you have taken histology. |
|
|
40:52 | don't offer it. All right. The submucosa just sits underneath the mucosa |
|
|
40:56 | then we have a couple of layers muscles. So in this particular |
|
|
40:59 | we have three layers, there's just couple of tissues or a couple of |
|
|
41:03 | that have three layers of muscles. right. This just happens to be |
|
|
41:07 | of them. The uterus is another . Um And then outside that we |
|
|
41:11 | the advent tissue, which is just tissue to keep the bladder from ripping |
|
|
41:14 | as it fills up. It's basically tissue that prevents it from overstretching. |
|
|
41:19 | What's unique about the bladder is its at the base of the shape, |
|
|
41:23 | is not well shown here, but can see it more clearly here is |
|
|
41:26 | has a funnel shape at its So that means the lowest point is |
|
|
41:31 | , always, always at the So when the bladder fills up, |
|
|
41:35 | flows in and it goes to that point, it's not gonna collect in |
|
|
41:38 | pouch in a special spot or anything that. All right, you can |
|
|
41:42 | where the openings of the ureters So between the ureters and the |
|
|
41:46 | that would be what is referred to the trigone. And so it's basically |
|
|
41:49 | lowest point. So fluid flows in bladder fills up and then after the |
|
|
41:55 | fills up and it's time to What we're gonna do is we're gonna |
|
|
41:58 | urine through the urethra. The urethra two sphincters to it. All |
|
|
42:04 | The first sphincter is what is referred as the internal urethral sphincter. And |
|
|
42:08 | second one is the external urethral The internal, one is smooth |
|
|
42:12 | The external one is skeletal muscle. I control my smooth muscle? But |
|
|
42:18 | I control my skeletal muscle? So what we have here is we |
|
|
42:23 | two doors, two gates between the and the bladder, right? One |
|
|
42:28 | open on its own. The other you have control over. All |
|
|
42:33 | that's the idea here. So this the one when the bladder stretches, |
|
|
42:39 | internal urethral sin, the the bladder . And what it does is it |
|
|
42:42 | that muscle and causes it to And so that allows for urine to |
|
|
42:48 | through that point once you open up external urethral sphincter. So you go |
|
|
42:54 | the bathroom, right? You fill urgent class. So you head on |
|
|
42:57 | the bathroom, you go into the , you drop trout as the guys |
|
|
43:01 | say, I don't know what ladies , lift skirt, I don't |
|
|
43:04 | Um And then what would happen is do this right? I mean, |
|
|
43:09 | about it and what are you You're relaxing the external urethral sphincter. |
|
|
43:18 | right. So those two things have happen in order for you to actually |
|
|
43:23 | the fluid. All right. I mentioned this already. The female |
|
|
43:28 | is actually rather short and its sole is for the evacuation of urine from |
|
|
43:33 | bladder. The male urethra has multiple . It is not just a pathway |
|
|
43:38 | the bladder and the bathroom. It has. And you can't see in |
|
|
43:42 | picture on purpose, openings with the uh duct defines um the vast ephrine |
|
|
43:49 | which is part of the pathway for during the process of ejaculation, which |
|
|
43:54 | get to. In the third, last unit maturation is the fancy word |
|
|
44:01 | saying uh urination or avoiding. Those all the polite ways. You |
|
|
44:07 | peeing is the, I guess the year old way to say it. |
|
|
44:12 | There are two re reflexes involved, storage reflex and the maturation reflex. |
|
|
44:17 | , storage reflex, this is what doing when we're filling our bladder. |
|
|
44:21 | two things are going on. We sympathetic stimulation and we have somatic |
|
|
44:25 | Why do we need two different types stimulation? Two different types of |
|
|
44:30 | All right. So, with regard the sympathetic stimulation that is causing the |
|
|
44:37 | ? Huh? Yeah. The relaxation the detrusor muscles. All right. |
|
|
44:43 | what we're doing, the detrusor muscles the muscle name the named muscles of |
|
|
44:46 | bladder. And so what's happening is it's filling up, the sy sympathetic |
|
|
44:51 | is saying, keep relaxing, keep , keep relaxing and allowing your bladder |
|
|
44:55 | fill up. All right. The thing that it's gonna do is it's |
|
|
44:59 | continue to contract that internal sphincter. , remember, we don't want during |
|
|
45:05 | , we don't want uh urine to the bladder. So the sympathetic activity |
|
|
45:10 | allowing the bladder to expand, but also preventing that uh sphincter from relaxing |
|
|
45:17 | then the somatic stimulation, this is done through the pedal nerve. I'm |
|
|
45:21 | gonna ask you that it's not an class, but what you're doing is |
|
|
45:24 | clamping down and holding that external sphincter this. So, basically, you're |
|
|
45:28 | think of both doors are slammed shut I'm not letting anything out. |
|
|
45:34 | then it's time to pee. All . So, um, autonomic somatic |
|
|
45:40 | , I, is this the same ? Do I even bother racing stuff |
|
|
45:44 | the last night? I probably didn't . So this is the four |
|
|
45:48 | All right. First off, bladder gonna fill up roughly about 200 to |
|
|
45:51 | mils. All right. So we average it out, call it |
|
|
45:55 | So you fill up and what do get? All right. Well, |
|
|
46:00 | gonna get pressure inside that bladder. you're gonna detect that pressure that's sends |
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46:05 | signal up to the pond. The says, hey, uh, let's |
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46:08 | ahead and start contracting that, those, uh, detrusor muscles. |
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46:13 | the detrusor muscles begin to contract because the expansion of the bladder. What's |
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46:18 | in the eternal sphincter, it's beginning relax. And so you have two |
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46:22 | going against you now, right? feel the pressure on the bladder and |
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46:27 | have a sphincter that is opened But does urine come? No, |
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46:34 | wouldn't it come? You have to the second step. Right. You |
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46:38 | to open up the second door. , while you're sitting in class, |
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46:41 | sat there and you drink your big of water. Right? And all |
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46:45 | a sudden all that water has found way into the bladder. You hit |
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46:48 | 300 mark and all of a sudden feel that I gotta pee but you're |
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46:53 | class and you're polite and you don't up and walk out. Right? |
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46:56 | do you do? You sit there say go away, Pete, I'm |
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47:01 | , it's not time yet. You even do a little bit of a |
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47:05 | , right? And then what happens after about five minutes or so that |
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47:10 | goes away and the bladder continues to . All right. So that's |
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47:15 | If you ignore the reflex, it keep going on until you get about |
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47:21 | 200 or so down the line. then eventually what will happen if you |
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47:26 | ignoring it is your body just says you. I know what's best for |
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47:30 | and it will relax that muscle on own and then you will wet yourself |
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47:34 | you will become an internet me, ? Or at least a photo that's |
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47:39 | around amongst your friends at parties at times when it's most embarrassing to |
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47:44 | All right. Either one works, in the absence of you blowing it |
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47:49 | and you find your way into the , then that's when you're going to |
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47:54 | the bladder. And in essence, you're doing is you are going to |
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47:58 | that sphincter, that external sphincter. then because of the contractions of the |
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48:03 | muscle, that's gonna press the urine of the bladder and out through the |
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48:10 | today, you can go home and your parents, hey, I learned |
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48:14 | to pee. They'll be so proud they're spending so much money on this |
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48:21 | . Now, when you were a , most likely when you were a |
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48:28 | , did your mother ever look you the eye before a trip and say |
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48:32 | to the bathroom? Yeah. And went and what did you say to |
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48:37 | ? I don't need to go. then what did she say? Get |
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48:41 | that bathroom right now and go We're about to go on a long |
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48:43 | trip just downtown because I know the we get in the car, what |
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48:46 | you gonna need to do? You're need to pee. So what do |
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48:49 | do? You go in the bathroom what do you do? You |
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48:53 | All right. So how does that ? Well, it has to do |
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48:56 | the abdominal pressure onto the bladder? . What you're doing is you're creating |
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49:01 | , that pressure is detected by those receptors, which sends that signal up |
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49:05 | the autonomic nervous system through the ponds down again and causes the contraction of |
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49:11 | muscles. All right, that's all doing is you're forcing it to |
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49:15 | So, it is a response that not, the bladder itself is not |
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49:21 | . It's an autonomic response as a of the somatic pressures that you're putting |
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49:26 | your bladder. All right. That sound like something you've done. Has |
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49:32 | ever picked you up? And you , please stop squeezing me, you're |
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49:34 | make me pee. No, I'm around the room, I'm su |
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49:39 | it's had to have happened at least . All right, usually to women |
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49:45 | don't admit to it, you Well, we don't get picked up |
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49:49 | that often. But anyway, we have 30 minutes, 30 minutes |
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49:56 | describe cause I don't feel like you have questions. You guys are just |
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50:01 | at me like you should know. , go ahead. That. Why |
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50:08 | it autonomic because of the sympathetic and governing the, the bladder itself? |
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50:13 | , what we're doing is we're contracting , the, the sphincter, |
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50:18 | But we're also relaxing through sympathetic So the counter of that would be |
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50:24 | , causing contraction of that detrusor So that's what's actually causing the need |
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50:30 | pee I mean, again, what you doing if I'm forcing myself to |
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50:34 | . What I'm doing is I'm squeezing muscle that's pressing on the bladder and |
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50:39 | it presses on the bladder, it that cycle. That is the normal |
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50:44 | through the parasympathetic. That's why. it's autonomic that's doing the work. |
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50:49 | not. You doing the work? . It's a good question. All |
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50:56 | . Are we ready to deal with weird, the hard, I only |
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51:03 | one person on their head. Ready. All right. First |
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51:09 | where do you get your water Everyone thinks it's from my drink, |
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51:12 | I also get it from my OK. Go squeeze a steak. |
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51:16 | how much juice flows out of All right. There's water in |
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51:20 | All right, you lose water through skin, you lose water through the |
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51:25 | . You've seen that when it gets , breathe out, uh you lose |
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51:28 | through the process of defecation, you it through urination. So there are |
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51:32 | pathways. Water is lost from the . If your water levels get too |
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51:36 | , no sweat. The kidney just filter, filter, filter water goes |
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51:39 | and I get rid of that excess . We are designed to get rid |
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51:43 | excess water. But if I become , I cannot draw water from the |
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51:52 | . All right. Once I've made , remember what we said, it |
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51:55 | be altered. So I have to mechanisms to draw the water in before |
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52:01 | becomes actual urine. And the time becomes urine is after it passes through |
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52:06 | collecting duct and enters into the renal into those kiss that we described |
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52:14 | we are back at this picture of kidney and you can see where the |
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52:17 | are and what this is trying to you is the osmolarity that I was |
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52:22 | inside the kidney. So out here the cortex, you can see that |
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52:25 | osmolarity is around 300 million osmoles. when you go into the medulla, |
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52:29 | go from 300 down to 469 in milli osmos. And so you can |
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52:35 | if this is my center point moving that center point, I've got this |
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52:39 | that's moving from cortex down through the to create this very, very concentrated |
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52:46 | . In other words, there's less more. So that's all that we're |
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52:49 | here. I'm just using these terms just so that you remember. So |
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52:53 | hypo hyper, just in case you realize what that means. Hypo too |
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52:58 | water, hyper, too little All right. Now, if I |
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53:04 | too much water in my body, all I'm gonna do is I'm just |
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53:08 | allow the water to pass on right? But if I am |
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53:13 | I want to reclaim that water before ever gets down into these yellow |
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53:19 | And so what I can do is can reclaim that water and create urine |
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53:23 | varying concentrations in other words, the that are gonna match this osmotic gradient |
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53:30 | now and then I have a BME E taking this class. You know |
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53:32 | A BME is, right? Biomedical . They look at this what we're |
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53:36 | to describe and they go wow, is so cool for those of the |
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53:41 | of the U universe. It's like is interesting. So here's our first |
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53:49 | , the countercurrent multiplier. This is the loop of Henley is. And |
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53:53 | that means, the countercurrent multiplier it has two aspects to it. |
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53:58 | see if I can find my little thing. Uh Here's my draw |
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54:02 | All right. So what we have is we have a loop that goes |
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54:05 | and a loop that comes down or branch that goes up and a branch |
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54:08 | comes down. So here we we're gonna move in. I'm just |
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54:12 | sure I'm following it, right. there's our descending. So there's that |
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54:14 | that, that is countercurrent. All . So the tubules are countercurrent to |
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54:20 | other. I'm gonna point this out because it's gonna become important later. |
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54:24 | notice the flow of the tubule look at the flow of the blood |
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54:31 | the vasa is that countercurrent. So have a countercurrent system there as |
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54:38 | So there's a lot of countercurrent countercurrent simply means the fluid is going one |
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54:43 | it turns on itself and goes the way. All right. So the |
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54:48 | countercurrent goes down, it reverses direction back up through the ascending limb. |
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54:53 | descending to ascending the multiplier par part going to have to do with a |
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54:57 | loop that is going to allow sodium come out and fill that area to |
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55:05 | that and create that osmotic gradient. right. So this is what that |
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55:09 | mallary Nephron is responsible for. All . Now that we're gonna look at |
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55:13 | bunch of different pictures that are all be saying the same sort of |
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55:17 | And I'm just trying to find one works for you. All right. |
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55:21 | here we have the Juma Nephron, can see the med versus the |
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55:25 | what the Jus Nephron does, it down deep. And so in doing |
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55:29 | what we're gonna do is we're going make the flow of the fluid coming |
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55:32 | with the osmolarity of that filtrate being like the rest of your body. |
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55:36 | is the rest of your body? is its osmolarity 300 milli osm. |
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55:41 | remember that number. It's gonna keep back to it. All right. |
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55:44 | what it's going to do is that is now diving through an environment that |
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55:48 | greater than 300. All right. then what it's going to do is |
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55:52 | going to come back up and going move through that greater than 300. |
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55:56 | on the other side, we're going have modified what that concentration of filtrate |
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56:02 | inside that tube. And in the , we're also gonna slightly affect the |
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56:07 | environment that we're gonna have to fix a result of this. All |
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56:11 | So what we're gonna do is we're move materials out and we're gonna move |
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56:14 | in and that is what is gonna us to establish that osmotic gradient. |
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56:19 | then because we're moving things in and , that means we're also destroying at |
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56:24 | same time. And so that's where vasa comes in and helps me to |
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56:27 | things back into the right places so I can maintain it. And this |
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56:32 | where it starts. All right. , I have here labeled descending lib |
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56:37 | then I have ascending limb labeled, easier to start with the ascending |
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56:43 | All right. So we're gonna deal the backside. Before we deal with |
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56:46 | front side, the ascending limb is for allowing sodium and urea to move |
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56:56 | the medulla of the renal cortex or the, of the kidney. All |
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57:01 | . So there's two halves to We have the thick portion, which |
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57:06 | the one that's nearest to distal convoluted . And what it does is it |
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57:10 | pumps out sodium. So if I'm pumping out sodium, what I'm doing |
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57:16 | I'm adding in a whole bunch of . And what does that salt |
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57:21 | It attracts water, but the ascending is not permeable to water. So |
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57:28 | water has to come from someplace or does it come from? Well, |
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57:33 | here on the descending limb, the limb is permeable just to water. |
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57:41 | when salt gets moved out, water on the other side. Now, |
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57:47 | we're looking at in this picture is looking at a single nephron, a |
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57:51 | is made up of hundreds of thousands nephrons. If you took a slice |
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57:54 | it, it looks like a bunch Swiss cheese because you're looking at ascending |
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57:58 | descending limbs and they're all next to other, right? This is just |
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58:02 | cartoon to help you focus in on thing. So if I'm moving salt |
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58:07 | of here, you can imagine right to it is an ascending limb that's |
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58:10 | water to come out. So if is leaving out of here, |
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58:16 | I'm gonna erase all the ink real . So here's my osmolarity 300. |
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58:21 | water is leaving on the ascending what's happening to the osmolarity inside that |
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58:29 | ? Is it becoming hypertonic or hypotonic ? So it's increasing in terms of |
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58:36 | concentration as it's going down? All . So when it gets back down |
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58:41 | , now, what we have is have a side that allows for salt |
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58:44 | leave when salt leaves. What's happening the fluid on the inside becoming hypotonic |
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58:50 | hypertonic hypotonic. So the salt is , pulling out water on the front |
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58:57 | , but on the backside, I'm the salt back out. And what |
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59:01 | up happening is I end up with fluid that has a much lower salt |
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59:09 | . Or let me put it another . I'm creating a filtrate, which |
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59:15 | hypotonic. I'm getting rid of excess . OK. So the first thing |
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59:21 | the, the osmotic gradient does that creating is allows me to create a |
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59:27 | that is very, very watery. natural state is to get rid of |
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59:36 | . All right. Now, here's horrible, horrible slide. I'm gonna |
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59:42 | right here and I'm gonna tell you now. So write this down. |
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59:46 | on to youtube, look up osmotic formation and there's gonna be at least |
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59:52 | dozen videos that will have an animation you can physically watch what's going on |
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59:58 | so that you can match the fluid down the uh descending limb and the |
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60:04 | moving up the ascending limb and the moving out and the water moving |
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60:07 | So you can see it all working that what you'll be watching there is |
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60:12 | these, this slide is basically telling is basically as a sodium leave and |
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60:17 | water matches the water going down or filtrate going down is becoming more |
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60:22 | But as it's going up, it's less concentrated. And over time, |
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60:25 | it's doing is it's creating this osmotic on the outside. All right. |
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60:30 | there's no good picture for me to you that and me coming up here |
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60:33 | wiggling my arms around doesn't do a job. I used to show a |
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60:38 | tiny video but it was a flash . And since flash is no longer |
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60:42 | since 19 or 2018 or something like . Well, we can't show you |
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60:46 | flash animations. It's easier for you go look it up. All |
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60:50 | So go look one, go watch of the videos. It's like four |
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60:53 | . All right. So now we this osmotic gradient. So out here |
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60:59 | the side, you can see we an osmotic gradient that osmotic gradient is |
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61:03 | result of the filtrate flowing through where is leaving where the water is |
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61:07 | All right. Now, what we're with that filtrate is it's passing |
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61:13 | out from the loop of Hindley up the distal convoluted tubule and then it |
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61:17 | right down through the collecting duct and collecting duct passes through the osmotic |
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61:26 | Now, I can use this to advantage. Now, the normal state |
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61:33 | that the filtrate that I've created is far more dilute than when it |
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|
61:37 | So I can get rid of excess , right? But in the event |
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61:42 | my body is becoming dehydrated, I have something that I just stimulate. |
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61:48 | . All I gotta do is open aquaporin and then water will go through |
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61:53 | osmotic gradient and then out into that gradient, bringing water back into my |
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61:59 | . And so I can create now very concentrated urine. So I can |
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62:08 | the urine passing through or really the passing through. It's not urine yet |
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62:13 | make something far more concentrated. And I have to do is introduce an |
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62:18 | . And the way that I introduce is through vas suppressant, right? |
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|
62:24 | the countercurrent multiplier is important because I off with a normal fluid that looks |
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62:31 | the rest of my body. I it through the process and I create |
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62:37 | that is dilute. And then I use that environment that I created to |
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62:45 | a urine that stays dilute or becomes , very concentrated depending upon my |
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|
62:51 | All right. So that's the And when I said this was |
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62:55 | this is where my brain turned And I said, countercurrent and what |
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|
63:01 | la la, la, la how many times did I do |
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63:04 | Do you remember three times? Uh But we got this other |
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63:12 | the vasa. All right. Do remember that picture that showed the blood |
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|
63:17 | and the blood vessels went around the and across the base of the pyramid |
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|
63:20 | then came back down and emptied, ? So let's imagine for a moment |
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63:26 | peritubular capillaries instead of going around the capillaries and coming back up and then |
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63:31 | around the outside and forming veins. , if they had just passed on |
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63:36 | and just went right through that osmotic , what they would do is because |
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63:40 | capillaries, you'd get capillary exchange and water would leave and salt would enter |
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63:45 | . And I'd basically destroy the gradient I just spent a lot of effort |
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63:48 | to build. And then I couldn't urine. That was a varying |
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63:54 | So what the vasa does, it that problem. And what you do |
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63:59 | remember, you go down and you're along the de the ascending loop because |
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64:04 | they're next to each other. So going up, one's going down and |
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64:06 | you come back the other direction uh to the ascending loop. And so |
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64:11 | looks like this. And again, a capillary. So it's just going |
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64:15 | exchange. So when I'm in a , very concentrated environment, what is |
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64:20 | the capillary? So if the surrounding is hyperosmotic, what is leaving the |
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64:26 | and into that osmotic gradient, what or salt water? And then as |
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64:32 | move back up through the osmotic what is returning back to the osmotic |
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64:40 | ? Salt? Right? And what's back into the tubule, the other |
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64:47 | water? So what I'm doing is picking up salt where it was poorly |
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64:53 | , moving it and putting it back it belongs. I'm taking water which |
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64:57 | poorly deposited and moving it back to it belonged. So in essence, |
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65:02 | I've destroyed environment by allowing water to in. I'm taking that water, |
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65:06 | it someplace so that it reestablished the in its proper balance. So what |
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65:14 | have is we have a countercurrent mechanism the loop of Henley that's creating the |
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|
65:18 | . We have a vas Urrea that maintaining it. Because every time I |
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65:21 | water and salt in and out of tubule, I'm actually not only |
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65:25 | but I could also be destroying and what I'm trying to do. |
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65:29 | in other words, let me come to this slide. When water is |
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65:38 | over here, I am destroying That's what I'm trying to get |
|
|
65:43 | So what is a vas erecta It's picking up that water and moving |
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|
65:49 | up here as an example? All , that's the maintenance part. That's |
|
|
65:58 | this is trying to demonstrate. This Vas Urrea here. OK. And |
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|
66:08 | was the hardest thing we had to . The loop of Henley is responsible |
|
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66:14 | creating the gradient. When that the collecting goes through, I destroy |
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66:22 | . So the vas Urrea moves water salt back into its proper location so |
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66:27 | your osmotic gradient is maintained so that can make concentrated urine or water, |
|
|
66:35 | , urine depending upon need. am I getting blinky lights? Because |
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66:42 | getting late in the day? I blinky lights to eyes are like or |
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|
66:49 | this not making sense or let's move ? Because reasons I've already told you |
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|
67:01 | I first heard this, I didn't a lick of it. So if |
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67:04 | sitting there going. I have no what you're talking about. You say |
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67:07 | ? Nothing scary about that. Took three different times of taking this stupid |
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67:12 | and I still didn't get it. had to teach it to understand |
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|
67:19 | Yeah, I took it three Not that thing. No. So |
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|
67:28 | loop of Henley is responsible for creating osmotic gradient. Right. That's the |
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|
67:34 | part. Right? But when water through the collecting duct and the aqua |
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|
67:40 | are open water is able to And so what that does is when |
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67:44 | put water into a salty environment that it hypo osmotic relative to what it |
|
|
67:49 | . So I've just destroyed the osmotic that I created. So what does |
|
|
67:53 | vasa do? Because it's moving alongside loop of Hindley, it allows me |
|
|
67:58 | pick up that excess water or the if they're out of balance and re |
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68:04 | uh kind of redistribute them within the . So that, that osmotic gradient |
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68:11 | maintained. The other thing that it picks up the water and allows |
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68:14 | to send it to the excuse me the rest of the body, |
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68:19 | So that you can have the water your body and your body can use |
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|
68:24 | , which is really the whole goal the first place. Did that make |
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68:32 | sense? Yeah. Getting the half . The maybe if we ignore |
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|
68:49 | it will go away. Looks, , when you really have bingo it's |
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69:04 | , she said it better than You mean the capillary doesn't go straight |
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69:08 | if it did it would wreck Yes, it goes down and it |
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69:11 | back up so that it goes in out through the same path. Because |
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69:16 | you become a vein, once you an artery, do you have any |
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69:19 | of fluid exchange? No, which the vessels of exchange? Capillaries? |
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|
69:25 | capillaries, always, always, always . So once I become a |
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69:29 | I'm reestablished the structure. So nothing go in and out. So, |
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|
69:36 | going on now? All right, at the collecting duct. We want |
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|
69:40 | make water urine. All right. , that's the role of vasopressin. |
|
|
69:45 | right, vas suppressant acts on the com distal and uh convoluted tubule on |
|
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69:50 | collecting tubules and the collecting ducts to uh say, hey, um right |
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|
69:55 | you don't have aqua porns. They're sequester way on vesicles. What I |
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70:00 | you to do is I want you make aqua porns and I want you |
|
|
70:02 | move those vesicles up to the And when doing so, what's gonna |
|
|
70:05 | is that now, water can now through those structures? All right. |
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70:12 | water escapes through, then what you're do is you're gonna raise blood |
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|
70:15 | So here is a VP uh without VP. So you can see here |
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|
70:19 | go from 300 I become concentrated. worry about the numbers. I become |
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70:23 | dilute and then when I pass I stay dilute. All right. |
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|
70:29 | I sent me getting rid of excess when you drink a jug of |
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|
70:33 | This is what's going on. But been outside in the Houston Sun all |
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70:37 | long. You've been uh messing You haven't been drinking your water like |
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70:41 | taught you right? So what happens your body says I need water and |
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70:47 | fool is not getting me any. what I'm gonna do is I'm gonna |
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70:50 | a vpavp comes along and it introduces aqua porn. So even though I |
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70:55 | start off as a concentrate and I up as a dilute out here. |
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70:59 | ends up happening is that water passes , that filtrate, passes through water |
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71:03 | to escape. And so what I up with is a filtrate that is |
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71:07 | concentrated, that is vasopressin role as function of that water increases blood |
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71:17 | That's the easy way to think about . Now, sodium load is that |
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71:30 | little thing that sits so far off the side. This is the one |
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71:33 | we watch our salt because we don't have high blood pressure. All |
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71:38 | So in the proximal convoluted tubule in loop of Henley, we already said |
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71:42 | percentage of sodium is being reabsorbed. just a constant rate. It's over |
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71:47 | the distal convoluted tubule where it's oh if I have low salt and |
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71:53 | low salt would also be an indicator low water. Then what I need |
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71:59 | do in order to bring in more is I need to pump in |
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72:03 | And this is where aldosterone comes into . And what we use is we |
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72:07 | this more complex system called the Renan and aldosterone system. Don't let the |
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72:13 | scare you. It's not that All right. So where was Renan |
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72:20 | ? Do you remember? And the someplace not the adrenal g it's in |
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72:27 | kidney, it was in the I'll do this. Remember. What |
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72:36 | I have? I had the afer , I had the eer arterial, |
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72:40 | glomerulus and all the way around. then this is dis convoluted tubule. |
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72:43 | structure where those two things are connected each other is called the juxtaglomerular |
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72:49 | And so we had granular cells located the afer arterial. We had the |
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72:53 | den C located with the distal convoluted , distal convoluted tubule, maloa cells |
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72:59 | with the granular cells and say, , uh salt levels are low. |
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73:03 | an indicator that we need more uh flowing through here. So I want |
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73:07 | to go ahead and vasodilate. But I want you to start producing renin |
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73:11 | Rennin gets released out into the blood it's an enzyme. And that Rennin's |
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73:17 | is to break down a plasma protein in circulation in your body at all |
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73:24 | . And that plasma protein is called . All Right. So this is |
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73:31 | this thing is like. Oh, lots of stuff but where we |
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73:33 | we're at the jury apparatus, we're renin. Renin acts on angiotensinogen causes |
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73:39 | to be converted into a T angiotensin one and angiotensin one circulates into |
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73:48 | parts of the body. And one the places it goes to is the |
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73:50 | and inside the lungs, we have enzyme called angiotensin converting enzyme ace, |
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73:59 | a cool name for such a boring and it converts A T one into |
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74:03 | T two. Now, there's also A T three and an A T |
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74:07 | , but we don't know what they . So we're just gonna ignore them |
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74:09 | T two. Now is the important . It is the molecule of great |
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74:15 | because it is responsible for a whole of things. One of the things |
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74:19 | responsible for is to tell your adrenal . Hey, um we need you |
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74:24 | start pumping salt into the body so water can come in. And so |
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74:27 | causes uh the uh sodium potassium pumps be introduced into the distal convoluted |
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74:34 | So I start pumping sodium into the convoluted tubule and wherever sodium goes water |
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74:42 | . So, Doster plays an important of moving sodium into the body. |
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74:47 | that water comes into the body and counters the low blood pressure as a |
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74:52 | of the low water. Ok. . Well, what does that look |
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74:57 | ? That's what it looks like So nice, simple model. Here |
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75:01 | have the NGO 10 SYO converted into T one gets converted by ace into |
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75:06 | T two. Tells aldosterone to come and says, hey uh stop, |
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75:11 | stop secreting uh sodium reabsorb sodium. in doing so you bring in |
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75:17 | So that's how you raise the blood . Oh That's not too bad. |
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75:21 | else does it do? There's Yes, there's more. So A |
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75:26 | two actually makes you thirsty. When am thirsty, I go grab a |
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75:32 | of water and I drink my Glug, glug, glug water goes |
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75:35 | my belly, belly into my What happens to my blood pressure? |
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75:40 | goes up. So through drinking I increase my blood pressure. But |
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75:46 | , there's more. It also stimulates . What now? Yeah. So |
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75:55 | is reso is produced in response to produced in. Do you guys remember |
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76:01 | it's produced posterior pituitary? Right? it's produced in response to the uh |
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76:08 | two to act on the collecting the collecting tubal distal convoluted tubal, |
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76:13 | the aquaporin. When I introduce What happens? Water goes back into |
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76:19 | body. Do you see, is a common thing and all these things |
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76:21 | bringing water into the body and then last one is, oh, by |
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76:24 | way, it's also a vasoconstrictor, we learned about it being a |
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76:28 | So if I make the space that's gonna raise the blood pressure. |
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76:32 | RAAS is a blood pressure razor, its job and it does. So |
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76:39 | increasing water fluid, you know, in the body, the volume of |
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76:43 | in the body and reducing the space the blood vessels. Ok? If |
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76:50 | want to see what all do and VP do in that loop, you |
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76:53 | throw it all in there and you find where you are. So there |
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76:55 | start with the ren and you can go through the whole thing. So |
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76:59 | is um acting on thirst receptor. a VP acting on the kidneys, |
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77:04 | yada yada. These are there just you to look at if you need |
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77:07 | follow the bouncing ball. If I something on, what do I need |
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77:13 | do? Turn it off. So have angiotensin aldosterone system in response to |
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77:19 | . We have a NP atrial natural peptide. Very, very scary. |
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77:25 | name for something very, very Atrial tells you where it's made. |
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77:28 | is it made? Atria naic? My goodness. What a horrible word |
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77:33 | from sodium na Naum, right? , have you ever wondered why sodium |
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77:40 | the symbol in a It's Naum. right. Nice German word to confuse |
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77:45 | . All right, etic urea So basically saying sodium in the urine |
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77:54 | then peptide tells you it's a So what it does is it counters |
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77:59 | and it does. So simply by just making sure I'm saying this |
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78:02 | Yes, inhibiting renin and aldosterone So if I block renin, that |
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78:08 | I brought block A T two. I block a 22, I block |
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78:12 | production. And oh, by the , why don't we just go ahead |
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78:14 | bypass those early steps and let's just aldosterone production by itself. And so |
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78:19 | doing so, I'm basically tipping it other direction. So instead of reabsorbing |
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78:24 | , what do I do is I those aqua porns. I'm no longer |
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78:28 | . I'm not bringing water in and just going to let it pass on |
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78:31 | and I can get rid of all excess water. And so what you're |
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78:34 | now is you're playing a balancing game these two systems, ras and A |
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78:39 | are just sitting there doing this all long trying to make sure I'm maintaining |
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78:44 | blood pressure and ensuring I have the water salt balance in the body. |
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78:49 | right. The other thing that it is the dilation of the Glom Afer |
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78:55 | . Remember I was constricting them in first place to increase the pressure uh |
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78:59 | drive uh fluid in. So that's we're doing. Yeah. Last little |
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79:06 | seemed like there were a lot of for this class, but a lot |
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79:09 | them are just like just click, , click. All right. These |
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79:12 | just some simple statements, statements, ? So in the tubular segments that |
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79:16 | permeable to water. So, reabsorption always always accompanied by comparable water |
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79:22 | Want that in English wherever sodium goes follows. Secondly, solute excretion is |
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79:29 | accompanied by a comparable water excretion. what that's saying is if I allow |
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79:33 | to stay in the, in my , then the water is gonna stay |
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79:37 | there. And so it's going to going to be lost. That's all |
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79:41 | saying. All right. So if is a loss or if there is |
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79:45 | gain of pure water that is not by a so deficit or excess, |
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79:53 | , then that's gonna change your ECF . That seems really dumb to say |
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79:59 | loud when I, when I say that way, in essence, if |
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80:02 | add in extra water, it affects molarity. That's all it's saying. |
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80:06 | right. Now, here's an if I drink pure water, what |
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80:11 | I have to pee because I now excess water in my body because my |
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80:15 | has become hyper osmotic or hypo right? The second part. If |
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80:23 | drink too much alcohol, none of have ever done that. Have |
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80:28 | OK? I didn't think so. that's gonna do? Alcohol is an |
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80:32 | of vasopressin. And when I inhibit , I no longer put those aquaporin |
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80:36 | place. And when I don't have aquaporin in place, that water leaves |
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80:39 | body? So what happens to me I drink alcohol? I become |
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80:45 | Right? And that's never happened to of us ever. Right. None |
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80:49 | us has ever had a hangover. hangover is a function of dehydration. |
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80:59 | . Just letting you know. there you go. That, that's |
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81:02 | kidney. Everything from here on out sailing. It is straightforward when you're |
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81:10 | with the kidney. What do we ? One end to the other |
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81:14 | And you're good to go that one two too too. How do you |
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81:24 | good. I got your emails. . Maybe. Let me see. |
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81:36 | trying to remember. What am I at? I look at a calendar |
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81:38 | Monday next week I want that. want that. I'm going to be |
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81:46 | a committee meeting all day long. . Mhm. Friday. This Friday |
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81:58 | think so. What time there? in my office? I work. |
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82:09 | right. I'm, I'm putting it . Ok. Actually I'm gonna put |
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82:13 | over here. How was today? huh. Yes. Like, like |
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82:18 | types of alcohol that are good |
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