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00:01 All right, y'all, you guys a good day. Yeah, it's

00:06 be raining on Thursday. I think heads up because I know you guys

00:10 to know about these types of All right. Um I made a

00:16 . Um I don't know if you the promise, but I said today

00:18 the most difficult day in terms of rest of the semester. Um And

00:22 not doing that again to scare I'm just trying to kind of perk

00:25 up to say, all right, a part where I'm gonna need to

00:28 attention and I'll point out was I'll say this is the time.

00:32 ? Right now, this is not time this actually uh this part of

00:35 lecture is actually pretty straightforward and we describing how a kidney goes through the

00:41 of filtration. We were looking at Nephron and we said, hey,

00:44 plasma is flowing into the glomerulus, glomeruli uh fluid is being pushed out

00:50 a series of pressure, right? Those pressures collectively are referred to as

00:54 net filtration pressure that drives fluid into tubular portion. And now we have

00:59 fluid, which is more than more than we are trying to get

01:02 of. And so we need to modify it. And what we call

01:06 filtrated fluid is just the filtrate. right, it's not urine yet.

01:10 won't be urine until the end of class. Ok. So what we're

01:14 do next is we're going to reabsorb materials, the body wants to keep

01:20 the body. All right. So gotta think about it like this,

01:23 tubule is outside the body and we're to move things from outside the body

01:28 into the body, right? And that's what that first step is

01:32 Now, this is very, very . We're only gonna take in those

01:36 that we want to keep most of takes place in the proximal convoluted

01:43 So whenever we're talking about this we're just, we're just sitting up

01:46 at that front end. All Um We've already mentioned we're trying to

01:50 the things that we want. So statement I have a high reabsorptive capacities

01:54 the substances the body needs. That's I'm saying is if your body

01:58 it's going to keep it and anything your body doesn't want is just going

02:01 allow it to keep on flowing with filtrate. Remember what the filtrate

02:06 It is plasma minus the plasma right? So even though we give

02:11 a special name, it's not that different than what we've already started

02:15 All right. Um And so there's processes that we're gonna be looking at

02:19 or, or generally not looking but just generally that are taking place

02:23 that we have cells. And so have to add the pass through the

02:26 or have to pass between the So we're gonna take advantage of either

02:30 those two simple processes. I know seems stupid that I say that.

02:34 . All right. So what are gonna do is we're gonna pass through

02:36 cells or we're gonna pass in between cells. And so everything is gonna

02:40 dependent upon the permeability of those cells particular substances. And this is where

02:46 fall back on something we learned a time ago. You're like crap.

02:51 hope I didn't have to something I forgotten. This is actually pretty

02:56 Wherever sodium goes water follows, you that wherever water goes, everything else

03:03 . Taking into consideration osmotic uh ideals osmotic characteristics. All right. So

03:09 know that you know the rest of story of perme or the of this

03:13 of reabsorption. All right. if everything starts with sodium, we

03:18 need to know what sodium is OK. So in the first

03:22 sodium, 70% of the sodium or as it says, about two thirds

03:27 the sodium in the uh filtrate is to be reabsorbed through the uh proximal

03:34 tubule. All right. And this the stuff that we care about.

03:38 . This is where we say when the reabsorption is taking place at the

03:41 end over here in the pro this why. So it plays a pivotal

03:44 in the reabsorption of water, reabsorption glucose, reabsorption of amino acid reabsorption

03:49 just you name it. It's It's being reabsorbed. It starts with

03:54 because wherever sodium goes, water follows wherever water goes, other things follow

04:00 with it. All right. 25% of the sodium is gonna be

04:05 in the loop of Henley. All . Now, we're gonna, this

04:08 part of the thing that's gonna make , the that section if I say

04:11 difficult thing, this is part of role. And so what we're gonna

04:15 is we're gonna use this sodium to create an environment so that our bodies

04:21 create urine's ovarian concentrations. So we're describe that later. But that's the

04:27 why is because of the way that is being reabsorbed in the loop of

04:31 . The third place is the stuff your grandma cares about. Not you

04:35 much because, well, you're young you don't care about salt intake.

04:39 you know, grandma, she sits and looks at that salt and wonders

04:42 or not I'm gonna put it in food, right? And the reason

04:45 that is because sodium load becomes important is measured and it's in the distal

04:51 tubule where it has a key role ensuring the proper extracellular fluid volume.

04:58 other words, blood pressure is dependent salt. I'm gonna put that in

05:02 because it's not really true. It's true. All right. But the

05:07 of salt in the sodium reabsorption allows to bring water back into the body

05:11 this particular place. And it's what regulate to make sure water, our

05:15 salt balance is correct. All So your blood pressure and all the

05:20 pressure meds that everyone takes is focusing . All right. So three different

05:26 , three different rolls of sodium and are the key, the key

05:32 So let's look at the proximal convoluted . All right. So on the

05:39 side, so the Luminal side is the tube. This is where you're

05:42 see sodium channels, sodium glucose sodium exchangers. All right. So

05:49 in all three of these cases, am I doing? I'm moving sodium

05:53 its concentration gradient into the cell. this is a trans cellular transport.

05:58 right. Now, granted there is uh secondary active transport that's taking

06:03 but it's with the other materials, glucose and the amino acids. So

06:06 not really talking about them right So sodium goes into the cell and

06:10 I put sodium in the cell to sure that there is still flow into

06:13 cell, I need something to pump out of the cell. And so

06:17 the interstitial fluid side, I'm going have sodium potassium pumps. So what

06:21 doing is I'm allow sowing sodium which a higher concentration in the tubule than

06:25 the cell to move into the I pump it out. And so

06:28 creates a constant flow of sodium back the body. So far. So

06:33 , pretty straightforward, right, So sodium gets moved into the

06:40 moves to the other side of the into the interstitial fluid. So water

06:44 attracted to the sodium. So water now, where is water going to

06:48 ? Well, it can go through cells. We have aquaporin in

06:51 Aquaporin can be found throughout the, Nephron. We have aquaporin that are

06:57 open in the proximal convoluted tubules. water always follow sodium in the proximal

07:01 tubules. But when we get to distal end, so when you get

07:04 to the distal tubules, you get to the collecting ducts, you get

07:07 to the collecting tubules, the aqua are gonna be introduced at specific times

07:13 that you what you say is that exist in a closed state so I

07:17 open and close them based upon All right. So I'm gonna move

07:24 in when my body needs water further . But over the approximal co theta

07:31 water follows sodium easy peasy. All . There's also tight junctions that aren't

07:37 tight junctions, they're leaky. So leaks in between the cells as

07:42 Again, following salt. Now, you went back and tried to remember

07:48 the little tiny, stupid little anecdotes tried to make. I said sodium

07:52 water are like the cool kids at . And we said chlorine was like

07:57 , the guy in the friend right? So chlorine is gonna go

08:02 sodium goes, right? It's attracted to sodium. So it's going to

08:08 chlorine. So that's an easy thing do passive. You don't need any

08:15 to do. So just follows it as electrical gradient, potassium, potassium

08:21 gonna follow water because water is now an osmotic gradient. There's less or

08:27 more potassium now than in the interstitial . So potassium is gonna move into

08:31 cells. Now. Uh this is be done through paracellular rather than through

08:35 cellular mechanisms. When you get into nephronic loop, there's some uh res

08:40 there as well. Well, we're ignore that for right now. And

08:43 ultimately, when we get to the tubules, uh we're going to reabsorb

08:47 potassium. Actually, what we're doing we're doing an exchange here is potassium

08:52 protons and these are gonna be done the type a intercalated cells. So

08:56 absorb potassium and I give up a . And what do we say type

09:02 intercalated cells? What were they responsible acid secretion? So that's what really

09:07 the exchange is there. So that's you get rid of the extra protons

09:10 of your body. So, so as anything weird sodium goes in.

09:15 water goes in. So chlorine goes . So potassium goes in. So

09:21 goes in. Where's glucose going? , it's moving along with the sodium

09:26 again being pumped the other direction so . Does it sound like things that

09:30 body wants? Does your body want ? Did you stand in line at

09:35 long time at the chick fil A here to get your glucose?

09:40 Yeah. Uh huh I didn't even she, you're eating your chick fil

09:43 . So how long would we How long a wait was that was

09:45 30 minutes? 30 F-15 man. a long time to wait for good

09:54 . Then your amino acids, your acids are gonna do the same thing

09:57 got these co transporters. So sodium in amino acids going in, they're

10:02 the osmotic gradient as well. And we get to the weird one,

10:06 old urea, nitrogenous waste in Uh If you're not aware of

10:11 we don't just produce uh urea, actually produce a whole bunch of different

10:16 . So you have urea that's from breakdown, uric acid that's from nucleic

10:19 breakdown, creatinine, that's from creatine . So you're, you're producing different

10:25 of nitrogenous waste. And so uh of those are being produced, they

10:30 have to, uh, leave the . Um, and actually we're really

10:34 when it comes to uric acid. , and I'm not gonna go into

10:37 , but that's uric acid is the that leads to gout when we can't

10:41 uric acid properly. Um, that's gout is, but we're more interested

10:46 urea because that's the primary form of waste. All right. So,

10:52 what we said about Yuria, urea slow. They're like your slow

10:57 Actually, I don't know if I've explained Uria to you. Have I

11:00 I, OK. So you're like slow friend. They, they,

11:02 still follow along. It's, it's of the crowd, right? It's

11:06 the fringes. It's cruising along with , but it's a lot slower.

11:09 , it's the dumb jock friend, know, I mean, again,

11:12 got to think of the stereotypes and he the, the what? You

11:16 , whatever. All right. So follows along but it does so

11:22 It doesn't, it doesn't reabsorb at same rate. And what ends up

11:26 is, is that in the proximal tubule, you reabsorb about half of

11:30 Urea that's located in the filtrate. then when you get down to the

11:34 of Henley, then the loop of says, no. Uh II I

11:37 you back in the body. So starts pumping it back out and so

11:41 get rid of it all and then slowly moves back in, when you

11:44 to that distal end of the So down in the collecting tubes.

11:48 so what ends up happening is instead getting rid of all the urea that

11:51 body is producing, you maintain a amount of urea in your body.

11:58 in particular, that urea becomes really important because it's gonna play a

12:02 along with the sodium to help maintain create that osmotic gradient that I keep

12:10 to. OK. So it's there a reason. It's not just,

12:16 , we can't get rid of it we just live our lives. All

12:20 . So how many slides was Like 12, something like that?

12:26 don't know. 10. All And so that took us 12 minutes

12:30 go through. You already know how Nephron works. Wherever sodium goes,

12:35 follows wherever water goes, all the things follow. And it's as simple

12:41 that. Anyone who teaches you they're just trying to make it scary

12:46 , and hard. OK. So the first part. So we

12:52 we have all this stuff that we wanna keep, but it's stuck

12:56 So we move it out through that of reabsorption. We start off with

13:00 um what was, what did we ? It was 100 and 20

13:03 100 and 20 mil. And so we're doing is we've removed roughly 19

13:08 , 100 and 19 mils back into body of water and all these salts

13:12 glucose and amino acids. All But there are things in your body

13:19 either can't be filtered or are not efficiently. And so there are things

13:24 want to get rid of. All , you guys have heard about the

13:28 of consuming poppy seeds, right. . If you go have a poppy

13:33 bagel, are you supposed to go a drug test that week? That

13:37 ? No. All right, because down the poppy seed results in a

13:44 signal for opiates because poppy seeds are seeds of the poppy plant, which

13:48 where you get the materials for It's basically an opiate. All

13:53 So what this is, is a that's telling your body is metabolizing

13:59 And so you have toxins in your and sometimes you can only get rid

14:03 the toxins at a very specific In other words, at the rate

14:06 filtration, but some toxins, you want to get rid of a lot

14:11 . And that's what the third process . Is this process of secretion.

14:16 right here, what we're doing is doing a type of trans cellular

14:20 It needs to be active because what are doing is we are grabbing things

14:24 saying I am pumping you into the . So we're going from the blood

14:29 the tubule, we're not filtering, is blood that has gone through the

14:33 process is now moving through the peritubular . All right. And what does

14:39 mean again next to the tubule? . So these are uh capillaries that

14:45 right next to the tubule. And you have machinery carriers that are literally

14:50 of binding certain molecules and moving them and across the tubular surface into the

14:59 . Now, two things that are , really simple is the potassium and

15:03 protons. All right. So proton is gonna occur along the entire length

15:08 it's gonna be dependent upon your acidity the body body. The more protein

15:12 eat, the greater acidity your blood . All right. Vegetarians have less

15:18 blood, meat eaters have more acidic . It's just a function of eating

15:22 or proteins. All right. So that happens, the body says uh

15:27 I don't like that. So, I need to do is I need

15:29 get rid of those protons. And this is what you're using is using

15:33 mechanism to get rid of the right? Intercalated cells in particular are

15:39 for get getting rid of those protons exchange for reabsorbing potassium. But what

15:44 it say? It says across the length? I'm gonna go ahead and

15:47 . I'm trying to get rid of because I'm trying to maintain a very

15:51 blood. What about potassium? in the proximal convoluted tubule, we

15:58 abs reabsorbing the potassium, right? followed the water, it's in the

16:03 convoluted tubule where you're seeing potassium All right. And here what we're

16:09 is we're trying to maintain the appropriate concentrations. All right. Now,

16:15 me ask you a question. If were uh uh potassium deficient. What

16:19 you gonna go do? Eat a ? Actually, it turns out bananas

16:23 as potassium rich as we think they . But that's what we all

16:26 That's what they told us. So what we're gonna do, right?

16:29 so you can imagine, I'm just when I'm uh potassium deficient, one

16:33 the things I I know to do go eat my bananas. But one

16:37 the things your body is doing is , oh, instead of it going

16:40 and peeing it out, I'm gonna ahead and pull it back from the

16:42 . That's what it's trying to do it's doing it at the level of

16:45 convoluted tubule. All right. I know why this isn't advancing, but

16:50 we go. All right. So concentration is high in the plasma.

17:00 what it's gonna do is it's gonna into interstitial fluid and from the interstitial

17:04 , it's gonna be pumped by the potassium pump. All right. So

17:10 , that's what we're dealing with here in the distal convoluted tubule. All

17:15 . So what we're gonna do is going to exchange it. So the

17:18 that you should be looking for is here, right? So, if

17:20 get high potassium, right? What's happen is is I am going to

17:26 it into the tubular cells, So this is secretion. Look which

17:30 I'm going, I'm going out of body out into the tubule so that

17:34 can be secreted. So I pump into the tubular cell and then it

17:39 through its potassium channel and out it goodbye. Good rhythms. All

17:44 And what do I exchange for Well, I have exchangers as

17:49 Actually, that's not right. Oh saying, yeah. So here is

17:55 exchange is taking place paracellular. But me point this out and make it

18:00 , really crystal clear. The thing becomes really important about this. The

18:06 that I use to determine when I potassium out of the body is dependent

18:13 the hormone aldosterone. All right, is what aldosterone does when I am

18:22 low in water or basically my blood decreases. Or if my potassium levels

18:28 , what's gonna happen is that results a production of aldosterone from the adrenal

18:33 that aldosterone acts on the de the principal cells in the distal convoluted tubule

18:38 causes them to do two things. , increased number of sodium potassium

18:44 When I do that, I'm gonna pumping potassium out of the body.

18:48 also doing what in the name sodium pump and potassium potassium out of the

18:57 . So what am I doing? coming in? And where sodium

19:01 water follows. So that's gonna be blood pressure. All right, that's

19:06 idea is what it's doing there. if I just pump potassium into those

19:10 cells, it still needs to have way to get out of the tubular

19:13 . And so this is causing those cells, those tubular cells to introduce

19:18 potassium channels. So the potassium can flow on out. So, aldosterone

19:22 the hormone that's being produced to allow to secrete the potassium. But you

19:29 it also as a secondary role, we'll get to it. I've already

19:32 told you, it allows me to sodium into the body. And if

19:35 pump sodium into the body, I water in the body. If I

19:38 water in the body, I raise blood pressure. So aldosterone has a

19:42 role allows me to secrete the It allows me to increase blood

19:49 Ok. Yes, sir. By it's sorry, it should be a

20:01 amount of potassium in the body, ? So the idea is I'm trying

20:05 get rid of potassium. I wanna it. It's not, I'm not

20:09 low. That's I I'm backwards. my apologies. Good catch gold

20:17 I don't pass out gold stars every . I should though. But there's

20:23 else that you put in your body I already mentioned it. I said

20:25 the poppy seeds, right? Uh day, all day long, you're

20:30 materials and you are building up toxins your body, right? And so

20:34 body wants to get rid of So, um let's do it this

20:41 . We'll see how, how knowledgeable are on your drugs. How often

20:45 you allowed to take an Ibuprofen every hours? How often are you allowed

20:52 take acetaminophen? Four hours? How an Aleve 10 man? Why do

21:04 know all these things? Doctor Because I have four kids and you

21:06 to manage fevers sometimes. All Why do they all have different

21:13 I mean, they all do the thing, right? I mean,

21:16 mean, some are in a, are not some working the liver,

21:19 are processed through the kidney. But , why, why do they all

21:22 different times? What do you think , what half life? Ok.

21:31 yes, that's what I'm looking for basically they're metabolized differently and so they

21:35 metabolites at a specific rate. And there's another half which we'll get to

21:39 a second, which is their plasma . All right. But in

21:42 you break them down and if you them down faster than you can get

21:45 of them, those toxins will build and cause all sorts of horrible problems

21:49 you, right? So this is . You can do the same thing

21:54 vitamin C, right? You notice , have you ever, do you

21:58 eat vitamin C? Do you take C. So when I was,

22:02 I was just like, y'all's you know, you go down to

22:04 GNC and you'd get like a big of the, the orange flavored,

22:09 know, vitamin C and it's oh, I don't know, sweet

22:12 , you know, just start popping . All right. But if you

22:15 read the back, it's like, is the maximum amount you can take

22:18 a day? You guys know 3000 after 3000 mg, you're starting to

22:25 into toxic doses of vitamin C. ? Yeah, don't, don't do

22:30 . That's bad. It starts destroying . All right. But basically you

22:34 , there's a certain rate at which can get rid of the vitamin

22:37 All right. Now, the process filtration is a fixed rate.

22:44 So that's what we talked about the , right? The glome filtration

22:48 it sits more or less at at a constant rate depending on what

22:52 doing. I mean, if you're up sitting down, it makes small

22:55 to maintain within a certain range. so the fluid that happens to be

23:01 the materials that happen to be in filtrate at the time are gonna be

23:04 at that rate, right? But I have something I need to get

23:08 of, I'm gonna use this method secretion so I can get rid of

23:13 faster. All right. So this why we end up with like poppy

23:18 and stuff in our body or not seeds, but the the stuff.

23:21 so what we have is we have incredibly unique system that is highly

23:26 And beyond what we're going to talk here in the class because there is

23:29 one molecule, there are hundreds of specialized carriers that recognize anionic metabolites and

23:38 capable of binding them, grabbing on them and then moving them over into

23:43 filtrate. This is what some of look like. Ok. That's what

23:48 trying to show you these molecules that listed down there. Actually, I

23:52 anions, it looks like I was . It's C ions, my my

23:55 . All right. So what this is you're no longer dependent upon the

24:03 rate to get rid of the Your body is looking for ways or

24:07 discovered ways to get rid of toxins a faster rate than normally would occur

24:14 of this process of secretion. So not just potassium and it's not just

24:21 , it's metabolites of things that we . All right, whether it be

24:26 we eat or drug we take, it's a hormone that we're breaking

24:33 This is what this mechanism allows us do and it hastens the rate of

24:40 so that their toxic levels do not . Ok. So, so

24:47 so good. So the process that nephron goes through three steps, first

24:54 is filtration discriminate, non discriminate, discriminate, just pressure is just

25:06 it's bulk flow, absorb or Discriminate, non discriminate, discriminate,

25:13 picking, picking the winners and the . And then finally, secretion,

25:18 , non discriminate, discriminate, it's which things are going. If you

25:25 have the right channel, the right to pick up the thing, then

25:29 thing is stuck in the blood and follows all the rules. I

25:33 all this, you know, the example I used, I used to

25:37 and I apparently I just confused everybody no one really learns the law of

25:41 law of mass averages or law of action as well as they should.

25:47 you can imagine in circulation, let's you have um four molecules, I'm

25:53 stay with simple numbers, right? let's say you filter two,

25:58 But let's say that those are free . Let's say you have also four

26:02 bound up, right? And I to get rid of more of those

26:06 . The way that I can get molecules unbound is by removing them from

26:11 environment, right? The the the ones. Did you guys learn that

26:15 one point a long time ago in ? Two, maybe, maybe

26:20 you learn that this idea of free bound molecules. OK. Um When

26:25 saw the furrowed brow that scared me a moment, but then it was

26:27 , oh yeah, yeah. All right. So one of the

26:30 that we're doing here is we're forcing out of the system faster because you're

26:36 with the ratios of free to bound . Because if I'm moving, if

26:41 removing bound molecule or free molecules that means they're getting unbound quicker,

26:46 I can pick them up faster if makes sense. But if that confuse

26:51 don't worry about it. Just understand is a mechanism of quicker removal.

26:59 , are you with me? Three ? Yes, sir. Almost.

27:08 quite well. Maybe. Now I think about pocket M and MS and

27:16 this is true, well, so Pocket M and MS, those

27:21 be like your bounds. Can't, eat a pocket M and M until

27:25 becomes a hand. M and you're gonna remember that till the day

27:30 die. You know that right? gonna be 40 years old and you're

27:33 explain to your kids in a biology . All right. This I think

27:37 understand. M and MS and All right. Are you ready to

27:46 on to something different? How many you have ever peed in a

27:52 Everyone better raise their hand. If been to a doctor, you peed

27:56 in a cup. And what are doing? They ask you to pee

27:58 the cup. They put you put on the tray with your name on

28:01 , right? Have you ever do ? And then they go take your

28:06 why are they doing this? What they checking on? No, unless

28:12 a drug test. All right, doesn't care if you're on drugs,

28:16 you're lying to him. In which he needs to know or she needs

28:18 know. So that whatever they're prescribing you is not contraindicated. What

28:23 doing is they're checking your GFR. , typically they don't need to do

28:28 specific test that we're about to But usually what they're doing is they're

28:32 at your creatinine levels and they look your creatinine levels in the blood and

28:36 creatinine levels in your urine. And they measure your GFR based on that

28:40 GFR being your glomerular filtration rate, ? And your GFR is an indicator

28:46 kidney function. If your GFR is relative to the average, that means

28:50 kidney is not working appropriately. So one of the things that they're always

28:55 when you go to the doctor, check your blood pressure with the little

28:58 single mammon meter. See I got off without thinking about it right.

29:04 check your blood ox with the little oximeter, right? And then they

29:10 go pee in a jar or pee a cup and then set it on

29:13 tray and then a couple days you can log in and you can

29:16 your numbers right. And they're looking your, you know, your GFR

29:21 that relative to your blood. the proper way to measure GFR through

29:27 function is making sure, you know much stuff is actually there because they're

29:32 creatinine production is constant and it's I mean, if you work out

29:38 frequently you're gonna make more creatinine. ? If you're a lump on the

29:42 , you're gonna make less creatinine. ? So, it's, it's

29:45 it's a very complex form. You actually go look it up on

29:49 They actually show you it's different for Americans than it is for,

29:53 uh Western Europeans. And they have formulas for everybody. You know,

29:58 , it's a load of fun, ? But what you can do is

30:02 pump somebody full of inulin, not pump, people full of insulin.

30:07 things happen. All right. So pump them full of inulin. What

30:11 inulin? Anyone's gonna quickly Google that boy. You don't have to.

30:16 were you inulin is a molecule that's in uh plants and it is a

30:25 that can be filtered through the filtration of the Nephron. So it's actually

30:31 small, even though if you look up, it looks really big and

30:34 , I think it's based, it's type of sugar if I remember.

30:37 . I can't, I'm not 100% , but it can't be filtered or

30:42 , it's filtered, but it can't reabsorbed and it can't be secreted.

30:47 if you go and measure, you , if you put in a uh

30:50 certain amount and then they go peak little bit later, you can

30:54 and then you go take the you can measure the inulin in the

30:56 . You can measure the inulin in urine. And then using those two

31:00 , you can then determine whether or your kidney is functioning by filtering

31:05 that, that inulin at a constant at a specific rate. So that's

31:09 they're doing here. And I'm gonna to bet that 100% of you have

31:14 had to be injected by it with because it's not something they do that

31:19 anymore. Now, it's all about formula. All right. But that's

31:22 best way to do it because you , you're putting in a constant amount

31:25 a finite amount or a fixed amount then you can measure it. And

31:29 you can use a formula like this a time course to see. All

31:34 , is this right? So, my concentration of urine of the

31:37 uh what is the volume of urine I'm collecting? Divided by the concentration

31:40 the inulin in the plasma that will you your GFR, I'm not gonna

31:44 you that formula. I'm just saying , it's a simple thing that you

31:46 measure right? Because it's being And what this is an indicator of

31:52 your ability of your kidney to filter specific amount of plasma from or of

32:00 substance. This is what plasma clearance . And I'm gonna, I gotta

32:03 the definition out loud because if I it wrong, I'm gonna screw it

32:06 for all of you. OK. clearance is simply the volume of plasma

32:13 of a particular substance per minute. it's not like, oh I cleared

32:19 a couple milligrams of the substance. saying the volume of plasma. So

32:26 what you're measuring is the volume of having been cleared over that period of

32:32 per minute. All right, different have different plasma clearances. Going back

32:41 the example, we used Ibuprofen, . I don't know what a leave

32:48 . I never bothered learning, but substance they're all cleared at different

32:54 And so if you took Ibuprofen every hours, because you're not clearing it

33:01 enough, Ibuprofen would build up cause if you are taking acetaminophen,

33:09 Actually, we found out it was more toxic than we realized. You

33:13 that about f four or five years when they're like, everyone stopped taking

33:17 and everyone stopped taking acetaminophen. They , it's there's a certain threshold at

33:22 point it becomes highly, highly So it's, you know, but

33:26 it's like every four hours, you clear out a dose of acetaminophen of

33:31 is it? 500 mg, I , or maybe 1000 mg, you

33:35 clear that out in four hours. if you take 4000 mg, you're

33:40 your luck. So what this really is it demonstrates like, hey,

33:46 , different drugs, do different So I need to be careful what

33:49 take and when I take it you suffer from horrible, horrible head

33:55 not migraines, just headaches or you can count but taking acetaminophen or

34:01 doesn't do any good. Does Yeah. Um, but like if

34:05 have kids, I'm, I'm gonna , I'm gonna use this example.

34:08 works for headaches too. I'm gonna you something here. I am not

34:13 medical doctor. All right, I'm to information I received from my medical

34:20 and all the nurses we worked with we had, we're dealing with our

34:23 and when they were sick. All . And they say, look,

34:27 you have a high temperature or give them a, one of the

34:31 , acetaminophen or Ibuprofen. All Now we said Ibuprofen is every six

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

34:42 you're desperate to get them to be , right? And sometimes bourbon is

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

34:59 down, you gotta get them So what do you give them?

35:02 you go ahead? It's like four later. Do you go ahead and

35:04 them the Ibuprofen? Yeah, you give them at the three hour

35:09 you can give them the acetaminophen and at the six hour mark, you

35:14 give him the Ibuprofen and then three later, you can give them the

35:17 and then you can give the So if you're struggling with like a

35:21 headache that won't go away, you do the same thing to yourself because

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

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

36:23 the material or you know, what the rate of metabolism? It's simply

36:27 rate at which you are clearing it the blood. Yeah, say

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

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

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

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

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

46:05 signal up to the pond. The says, hey, uh, let's

46:08 ahead and start contracting that, those, uh, detrusor muscles.

46:13 the detrusor muscles begin to contract because the expansion of the bladder. What's

46:18 in the eternal sphincter, it's beginning relax. And so you have two

46:22 going against you now, right? feel the pressure on the bladder and

46:27 have a sphincter that is opened But does urine come? No,

46:34 wouldn't it come? You have to the second step. Right. You

46:38 to open up the second door. , while you're sitting in class,

46:41 sat there and you drink your big of water. Right? And all

46:45 a sudden all that water has found way into the bladder. You hit

46:48 300 mark and all of a sudden feel that I gotta pee but you're

46:53 class and you're polite and you don't up and walk out. Right?

46:56 do you do? You sit there say go away, Pete, I'm

47:01 , it's not time yet. You even do a little bit of a

47:05 , right? And then what happens after about five minutes or so that

47:10 goes away and the bladder continues to . All right. So that's

47:15 If you ignore the reflex, it keep going on until you get about

47:21 200 or so down the line. then eventually what will happen if you

47:26 ignoring it is your body just says you. I know what's best for

47:30 and it will relax that muscle on own and then you will wet yourself

47:34 you will become an internet me, ? Or at least a photo that's

47:39 around amongst your friends at parties at times when it's most embarrassing to

47:44 All right. Either one works, in the absence of you blowing it

47:49 and you find your way into the , then that's when you're going to

47:54 the bladder. And in essence, you're doing is you are going to

47:58 that sphincter, that external sphincter. then because of the contractions of the

48:03 muscle, that's gonna press the urine of the bladder and out through the

48:10 today, you can go home and your parents, hey, I learned

48:14 to pee. They'll be so proud they're spending so much money on this

48:21 . Now, when you were a , most likely when you were a

48:28 , did your mother ever look you the eye before a trip and say

48:32 to the bathroom? Yeah. And went and what did you say to

48:37 ? I don't need to go. then what did she say? Get

48:41 that bathroom right now and go We're about to go on a long

48:43 trip just downtown because I know the we get in the car, what

48:46 you gonna need to do? You're need to pee. So what do

48:49 do? You go in the bathroom what do you do? You

48:53 All right. So how does that ? Well, it has to do

48:56 the abdominal pressure onto the bladder? . What you're doing is you're creating

49:01 , that pressure is detected by those receptors, which sends that signal up

49:05 the autonomic nervous system through the ponds down again and causes the contraction of

49:11 muscles. All right, that's all doing is you're forcing it to

49:15 So, it is a response that not, the bladder itself is not

49:21 . It's an autonomic response as a of the somatic pressures that you're putting

49:26 your bladder. All right. That sound like something you've done. Has

49:32 ever picked you up? And you , please stop squeezing me, you're

49:34 make me pee. No, I'm around the room, I'm su

49:39 it's had to have happened at least . All right, usually to women

49:45 don't admit to it, you Well, we don't get picked up

49:49 that often. But anyway, we have 30 minutes, 30 minutes

49:56 describe cause I don't feel like you have questions. You guys are just

50:01 at me like you should know. , go ahead. That. Why

50:08 it autonomic because of the sympathetic and governing the, the bladder itself?

50:13 , what we're doing is we're contracting , the, the sphincter,

50:18 But we're also relaxing through sympathetic So the counter of that would be

50:24 , causing contraction of that detrusor So that's what's actually causing the need

50:30 pee I mean, again, what you doing if I'm forcing myself to

50:34 . What I'm doing is I'm squeezing muscle that's pressing on the bladder and

50:39 it presses on the bladder, it that cycle. That is the normal

50:44 through the parasympathetic. That's why. it's autonomic that's doing the work.

50:49 not. You doing the work? . It's a good question. All

50:56 . Are we ready to deal with weird, the hard, I only

51:03 one person on their head. Ready. All right. First

51:09 where do you get your water Everyone thinks it's from my drink,

51:12 I also get it from my OK. Go squeeze a steak.

51:16 how much juice flows out of All right. There's water in

51:20 All right, you lose water through skin, you lose water through the

51:25 . You've seen that when it gets , breathe out, uh you lose

51:28 through the process of defecation, you it through urination. So there are

51:32 pathways. Water is lost from the . If your water levels get too

51:36 , no sweat. The kidney just filter, filter, filter water goes

51:39 and I get rid of that excess . We are designed to get rid

51:43 excess water. But if I become , I cannot draw water from the

51:52 . All right. Once I've made , remember what we said, it

51:55 be altered. So I have to mechanisms to draw the water in before

52:01 becomes actual urine. And the time becomes urine is after it passes through

52:06 collecting duct and enters into the renal into those kiss that we described

52:14 we are back at this picture of kidney and you can see where the

52:17 are and what this is trying to you is the osmolarity that I was

52:22 inside the kidney. So out here the cortex, you can see that

52:25 osmolarity is around 300 million osmoles. when you go into the medulla,

52:29 go from 300 down to 469 in milli osmos. And so you can

52:35 if this is my center point moving that center point, I've got this

52:39 that's moving from cortex down through the to create this very, very concentrated

52:46 . In other words, there's less more. So that's all that we're

52:49 here. I'm just using these terms just so that you remember. So

52:53 hypo hyper, just in case you realize what that means. Hypo too

52:58 water, hyper, too little All right. Now, if I

53:04 too much water in my body, all I'm gonna do is I'm just

53:08 allow the water to pass on right? But if I am

53:13 I want to reclaim that water before ever gets down into these yellow

53:19 And so what I can do is can reclaim that water and create urine

53:23 varying concentrations in other words, the that are gonna match this osmotic gradient

53:30 now and then I have a BME E taking this class. You know

53:32 A BME is, right? Biomedical . They look at this what we're

53:36 to describe and they go wow, is so cool for those of the

53:41 of the U universe. It's like is interesting. So here's our first

53:49 , the countercurrent multiplier. This is the loop of Henley is. And

53:53 that means, the countercurrent multiplier it has two aspects to it.

53:58 see if I can find my little thing. Uh Here's my draw

54:02 All right. So what we have is we have a loop that goes

54:05 and a loop that comes down or branch that goes up and a branch

54:08 comes down. So here we we're gonna move in. I'm just

54:12 sure I'm following it, right. there's our descending. So there's that

54:14 that, that is countercurrent. All . So the tubules are countercurrent to

54:20 other. I'm gonna point this out because it's gonna become important later.

54:24 notice the flow of the tubule look at the flow of the blood

54:31 the vasa is that countercurrent. So have a countercurrent system there as

54:38 So there's a lot of countercurrent countercurrent simply means the fluid is going one

54:43 it turns on itself and goes the way. All right. So the

54:48 countercurrent goes down, it reverses direction back up through the ascending limb.

54:53 descending to ascending the multiplier par part going to have to do with a

54:57 loop that is going to allow sodium come out and fill that area to

55:05 that and create that osmotic gradient. right. So this is what that

55:09 mallary Nephron is responsible for. All . Now that we're gonna look at

55:13 bunch of different pictures that are all be saying the same sort of

55:17 And I'm just trying to find one works for you. All right.

55:21 here we have the Juma Nephron, can see the med versus the

55:25 what the Jus Nephron does, it down deep. And so in doing

55:29 what we're gonna do is we're going make the flow of the fluid coming

55:32 with the osmolarity of that filtrate being like the rest of your body.

55:36 is the rest of your body? is its osmolarity 300 milli osm.

55:41 remember that number. It's gonna keep back to it. All right.

55:44 what it's going to do is that is now diving through an environment that

55:48 greater than 300. All right. then what it's going to do is

55:52 going to come back up and going move through that greater than 300.

55:56 on the other side, we're going have modified what that concentration of filtrate

56:02 inside that tube. And in the , we're also gonna slightly affect the

56:07 environment that we're gonna have to fix a result of this. All

56:11 So what we're gonna do is we're move materials out and we're gonna move

56:14 in and that is what is gonna us to establish that osmotic gradient.

56:19 then because we're moving things in and , that means we're also destroying at

56:24 same time. And so that's where vasa comes in and helps me to

56:27 things back into the right places so I can maintain it. And this

56:32 where it starts. All right. , I have here labeled descending lib

56:37 then I have ascending limb labeled, easier to start with the ascending

56:43 All right. So we're gonna deal the backside. Before we deal with

56:46 front side, the ascending limb is for allowing sodium and urea to move

56:56 the medulla of the renal cortex or the, of the kidney. All

57:01 . So there's two halves to We have the thick portion, which

57:06 the one that's nearest to distal convoluted . And what it does is it

57:10 pumps out sodium. So if I'm pumping out sodium, what I'm doing

57:16 I'm adding in a whole bunch of . And what does that salt

57:21 It attracts water, but the ascending is not permeable to water. So

57:28 water has to come from someplace or does it come from? Well,

57:33 here on the descending limb, the limb is permeable just to water.

57:41 when salt gets moved out, water on the other side. Now,

57:47 we're looking at in this picture is looking at a single nephron, a

57:51 is made up of hundreds of thousands nephrons. If you took a slice

57:54 it, it looks like a bunch Swiss cheese because you're looking at ascending

57:58 descending limbs and they're all next to other, right? This is just

58:02 cartoon to help you focus in on thing. So if I'm moving salt

58:07 of here, you can imagine right to it is an ascending limb that's

58:10 water to come out. So if is leaving out of here,

58:16 I'm gonna erase all the ink real . So here's my osmolarity 300.

58:21 water is leaving on the ascending what's happening to the osmolarity inside that

58:29 ? Is it becoming hypertonic or hypotonic ? So it's increasing in terms of

58:36 concentration as it's going down? All . So when it gets back down

58:41 , now, what we have is have a side that allows for salt

58:44 leave when salt leaves. What's happening the fluid on the inside becoming hypotonic

58:50 hypertonic hypotonic. So the salt is , pulling out water on the front

58:57 , but on the backside, I'm the salt back out. And what

59:01 up happening is I end up with fluid that has a much lower salt

59:09 . Or let me put it another . I'm creating a filtrate, which

59:15 hypotonic. I'm getting rid of excess . OK. So the first thing

59:21 the, the osmotic gradient does that creating is allows me to create a

59:27 that is very, very watery. natural state is to get rid of

59:36 . All right. Now, here's horrible, horrible slide. I'm gonna

59:42 right here and I'm gonna tell you now. So write this down.

59:46 on to youtube, look up osmotic formation and there's gonna be at least

59:52 dozen videos that will have an animation you can physically watch what's going on

59:58 so that you can match the fluid down the uh descending limb and the

60:04 moving up the ascending limb and the moving out and the water moving

60:07 So you can see it all working that what you'll be watching there is

60:12 these, this slide is basically telling is basically as a sodium leave and

60:17 water matches the water going down or filtrate going down is becoming more

60:22 But as it's going up, it's less concentrated. And over time,

60:25 it's doing is it's creating this osmotic on the outside. All right.

60:30 there's no good picture for me to you that and me coming up here

60:33 wiggling my arms around doesn't do a job. I used to show a

60:38 tiny video but it was a flash . And since flash is no longer

60:42 since 19 or 2018 or something like . Well, we can't show you

60:46 flash animations. It's easier for you go look it up. All

60:50 So go look one, go watch of the videos. It's like four

60:53 . All right. So now we this osmotic gradient. So out here

60:59 the side, you can see we an osmotic gradient that osmotic gradient is

61:03 result of the filtrate flowing through where is leaving where the water is

61:07 All right. Now, what we're with that filtrate is it's passing

61:13 out from the loop of Hindley up the distal convoluted tubule and then it

61:17 right down through the collecting duct and collecting duct passes through the osmotic

61:26 Now, I can use this to advantage. Now, the normal state

61:33 that the filtrate that I've created is far more dilute than when it

61:37 So I can get rid of excess , right? But in the event

61:42 my body is becoming dehydrated, I have something that I just stimulate.

61:48 . All I gotta do is open aquaporin and then water will go through

61:53 osmotic gradient and then out into that gradient, bringing water back into my

61:59 . And so I can create now very concentrated urine. So I can

62:08 the urine passing through or really the passing through. It's not urine yet

62:13 make something far more concentrated. And I have to do is introduce an

62:18 . And the way that I introduce is through vas suppressant, right?

62:24 the countercurrent multiplier is important because I off with a normal fluid that looks

62:31 the rest of my body. I it through the process and I create

62:37 that is dilute. And then I use that environment that I created to

62:45 a urine that stays dilute or becomes , very concentrated depending upon my

62:51 All right. So that's the And when I said this was

62:55 this is where my brain turned And I said, countercurrent and what

63:01 la la, la, la how many times did I do

63:04 Do you remember three times? Uh But we got this other

63:12 the vasa. All right. Do remember that picture that showed the blood

63:17 and the blood vessels went around the and across the base of the pyramid

63:20 then came back down and emptied, ? So let's imagine for a moment

63:26 peritubular capillaries instead of going around the capillaries and coming back up and then

63:31 around the outside and forming veins. , if they had just passed on

63:36 and just went right through that osmotic , what they would do is because

63:40 capillaries, you'd get capillary exchange and water would leave and salt would enter

63:45 . And I'd basically destroy the gradient I just spent a lot of effort

63:48 to build. And then I couldn't urine. That was a varying

63:54 So what the vasa does, it that problem. And what you do

63:59 remember, you go down and you're along the de the ascending loop because

64:04 they're next to each other. So going up, one's going down and

64:06 you come back the other direction uh to the ascending loop. And so

64:11 looks like this. And again, a capillary. So it's just going

64:15 exchange. So when I'm in a , very concentrated environment, what is

64:20 the capillary? So if the surrounding is hyperosmotic, what is leaving the

64:26 and into that osmotic gradient, what or salt water? And then as

64:32 move back up through the osmotic what is returning back to the osmotic

64:40 ? Salt? Right? And what's back into the tubule, the other

64:47 water? So what I'm doing is picking up salt where it was poorly

64:53 , moving it and putting it back it belongs. I'm taking water which

64:57 poorly deposited and moving it back to it belonged. So in essence,

65:02 I've destroyed environment by allowing water to in. I'm taking that water,

65:06 it someplace so that it reestablished the in its proper balance. So what

65:14 have is we have a countercurrent mechanism the loop of Henley that's creating the

65:18 . We have a vas Urrea that maintaining it. Because every time I

65:21 water and salt in and out of tubule, I'm actually not only

65:25 but I could also be destroying and what I'm trying to do.

65:29 in other words, let me come to this slide. When water is

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

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

66:08 was the hardest thing we had to . The loop of Henley is responsible

66:14 creating the gradient. When that the collecting goes through, I destroy

66:22 . So the vas Urrea moves water salt back into its proper location so

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

66:42 getting late in the day? I blinky lights to eyes are like or

66:49 this not making sense or let's move ? Because reasons I've already told you

67:01 I first heard this, I didn't a lick of it. So if

67:04 sitting there going. I have no what you're talking about. You say

67:07 ? Nothing scary about that. Took three different times of taking this stupid

67:12 and I still didn't get it. had to teach it to understand

67:19 Yeah, I took it three Not that thing. No. So

67:28 loop of Henley is responsible for creating osmotic gradient. Right. That's the

67:34 part. Right? But when water through the collecting duct and the aqua

67:40 are open water is able to And so what that does is when

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

68:04 uh kind of redistribute them within the . So that, that osmotic gradient

68:11 maintained. The other thing that it picks up the water and allows

68:14 to send it to the excuse me the rest of the body,

68:19 So that you can have the water your body and your body can use

68:24 , which is really the whole goal the first place. Did that make

68:32 sense? Yeah. Getting the half . The maybe if we ignore

68:49 it will go away. Looks, , when you really have bingo it's

69:04 , she said it better than You mean the capillary doesn't go straight

69:08 if it did it would wreck Yes, it goes down and it

69:11 back up so that it goes in out through the same path. Because

69:16 you become a vein, once you an artery, do you have any

69:19 of fluid exchange? No, which the vessels of exchange? Capillaries?

69:25 capillaries, always, always, always . So once I become a

69:29 I'm reestablished the structure. So nothing go in and out. So,

69:36 going on now? All right, at the collecting duct. We want

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

69:50 collecting tubules and the collecting ducts to uh say, hey, um right

69:55 you don't have aqua porns. They're sequester way on vesicles. What I

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.

70:12 water escapes through, then what you're do is you're gonna raise blood

70:15 So here is a VP uh without VP. So you can see here

70:19 go from 300 I become concentrated. worry about the numbers. I become

70:23 dilute and then when I pass I stay dilute. All right.

70:29 I sent me getting rid of excess when you drink a jug of

70:33 This is what's going on. But been outside in the Houston Sun all

70:37 long. You've been uh messing You haven't been drinking your water like

70:41 taught you right? So what happens your body says I need water and

70:47 fool is not getting me any. what I'm gonna do is I'm gonna

70:50 a vpavp comes along and it introduces aqua porn. So even though I

70:55 start off as a concentrate and I up as a dilute out here.

70:59 ends up happening is that water passes , that filtrate, passes through water

71:03 to escape. And so what I up with is a filtrate that is

71:07 concentrated, that is vasopressin role as function of that water increases blood

71:17 That's the easy way to think about . Now, sodium load is that

71:30 little thing that sits so far off the side. This is the one

71:33 we watch our salt because we don't have high blood pressure. All

71:38 So in the proximal convoluted tubule in loop of Henley, we already said

71:42 percentage of sodium is being reabsorbed. just a constant rate. It's over

71:47 the distal convoluted tubule where it's oh if I have low salt and

71:53 low salt would also be an indicator low water. Then what I need

71:59 do in order to bring in more is I need to pump in

72:03 And this is where aldosterone comes into . And what we use is we

72:07 this more complex system called the Renan and aldosterone system. Don't let the

72:13 scare you. It's not that All right. So where was Renan

72:20 ? Do you remember? And the someplace not the adrenal g it's in

72:27 kidney, it was in the I'll do this. Remember. What

72:36 I have? I had the afer , I had the eer arterial,

72:40 glomerulus and all the way around. then this is dis convoluted tubule.

72:43 structure where those two things are connected each other is called the juxtaglomerular

72:49 And so we had granular cells located the afer arterial. We had the

72:53 den C located with the distal convoluted , distal convoluted tubule, maloa cells

72:59 with the granular cells and say, , uh salt levels are low.

73:03 an indicator that we need more uh flowing through here. So I want

73:07 to go ahead and vasodilate. But I want you to start producing renin

73:11 Rennin gets released out into the blood it's an enzyme. And that Rennin's

73:17 is to break down a plasma protein in circulation in your body at all

73:24 . And that plasma protein is called . All Right. So this is

73:31 this thing is like. Oh, lots of stuff but where we

73:33 we're at the jury apparatus, we're renin. Renin acts on angiotensinogen causes

73:39 to be converted into a T angiotensin one and angiotensin one circulates into

73:48 parts of the body. And one the places it goes to is the

73:50 and inside the lungs, we have enzyme called angiotensin converting enzyme ace,

73:59 a cool name for such a boring and it converts A T one into

74:03 T two. Now, there's also A T three and an A T

74:07 , but we don't know what they . So we're just gonna ignore them

74:09 T two. Now is the important . It is the molecule of great

74:15 because it is responsible for a whole of things. One of the things

74:19 responsible for is to tell your adrenal . Hey, um we need you

74:24 start pumping salt into the body so water can come in. And so

74:27 causes uh the uh sodium potassium pumps be introduced into the distal convoluted

74:34 So I start pumping sodium into the convoluted tubule and wherever sodium goes water

74:42 . So, Doster plays an important of moving sodium into the body.

74:47 that water comes into the body and counters the low blood pressure as a

74:52 of the low water. Ok. . Well, what does that look

74:57 ? That's what it looks like So nice, simple model. Here

75:01 have the NGO 10 SYO converted into T one gets converted by ace into

75:06 T two. Tells aldosterone to come and says, hey uh stop,

75:11 stop secreting uh sodium reabsorb sodium. in doing so you bring in

75:17 So that's how you raise the blood . Oh That's not too bad.

75:21 else does it do? There's Yes, there's more. So A

75:26 two actually makes you thirsty. When am thirsty, I go grab a

75:32 of water and I drink my Glug, glug, glug water goes

75:35 my belly, belly into my What happens to my blood pressure?

75:40 goes up. So through drinking I increase my blood pressure. But

75:46 , there's more. It also stimulates . What now? Yeah. So

75:55 is reso is produced in response to produced in. Do you guys remember

76:01 it's produced posterior pituitary? Right? it's produced in response to the uh

76:08 two to act on the collecting the collecting tubal distal convoluted tubal,

76:13 the aquaporin. When I introduce What happens? Water goes back into

76:19 body. Do you see, is a common thing and all these things

76:21 bringing water into the body and then last one is, oh, by

76:24 way, it's also a vasoconstrictor, we learned about it being a

76:28 So if I make the space that's gonna raise the blood pressure.

76:32 RAAS is a blood pressure razor, its job and it does. So

76:39 increasing water fluid, you know, in the body, the volume of

76:43 in the body and reducing the space the blood vessels. Ok? If

76:50 want to see what all do and VP do in that loop, you

76:53 throw it all in there and you find where you are. So there

76:55 start with the ren and you can go through the whole thing. So

76:59 is um acting on thirst receptor. a VP acting on the kidneys,

77:04 yada yada. These are there just you to look at if you need

77:07 follow the bouncing ball. If I something on, what do I need

77:13 do? Turn it off. So have angiotensin aldosterone system in response to

77:19 . We have a NP atrial natural peptide. Very, very scary.

77:25 name for something very, very Atrial tells you where it's made.

77:28 is it made? Atria naic? My goodness. What a horrible word

77:33 from sodium na Naum, right? , have you ever wondered why sodium

77:40 the symbol in a It's Naum. right. Nice German word to confuse

77:45 . All right, etic urea So basically saying sodium in the urine

77:54 then peptide tells you it's a So what it does is it counters

77:59 and it does. So simply by just making sure I'm saying this

78:02 Yes, inhibiting renin and aldosterone So if I block renin, that

78:08 I brought block A T two. I block a 22, I block

78:12 production. And oh, by the , why don't we just go ahead

78:14 bypass those early steps and let's just aldosterone production by itself. And so

78:19 doing so, I'm basically tipping it other direction. So instead of reabsorbing

78:24 , what do I do is I those aqua porns. I'm no longer

78:28 . I'm not bringing water in and just going to let it pass on

78:31 and I can get rid of all excess water. And so what you're

78:34 now is you're playing a balancing game these two systems, ras and A

78:39 are just sitting there doing this all long trying to make sure I'm maintaining

78:44 blood pressure and ensuring I have the water salt balance in the body.

78:49 right. The other thing that it is the dilation of the Glom Afer

78:55 . Remember I was constricting them in first place to increase the pressure uh

78:59 drive uh fluid in. So that's we're doing. Yeah. Last little

79:06 seemed like there were a lot of for this class, but a lot

79:09 them are just like just click, , click. All right. These

79:12 just some simple statements, statements, ? So in the tubular segments that

79:16 permeable to water. So, reabsorption always always accompanied by comparable water

79:22 Want that in English wherever sodium goes follows. Secondly, solute excretion is

79:29 accompanied by a comparable water excretion. what that's saying is if I allow

79:33 to stay in the, in my , then the water is gonna stay

79:37 there. And so it's going to going to be lost. That's all

79:41 saying. All right. So if is a loss or if there is

79:45 gain of pure water that is not by a so deficit or excess,

79:53 , then that's gonna change your ECF . That seems really dumb to say

79:59 loud when I, when I say that way, in essence, if

80:02 add in extra water, it affects molarity. That's all it's saying.

80:06 right. Now, here's an if I drink pure water, what

80:11 I have to pee because I now excess water in my body because my

80:15 has become hyper osmotic or hypo right? The second part. If

80:23 drink too much alcohol, none of have ever done that. Have

80:28 OK? I didn't think so. that's gonna do? Alcohol is an

80:32 of vasopressin. And when I inhibit , I no longer put those aquaporin

80:36 place. And when I don't have aquaporin in place, that water leaves

80:39 body? So what happens to me I drink alcohol? I become

80:45 Right? And that's never happened to of us ever. Right. None

80:49 us has ever had a hangover. hangover is a function of dehydration.

80:59 . Just letting you know. there you go. That, that's

81:02 kidney. Everything from here on out sailing. It is straightforward when you're

81:10 with the kidney. What do we ? One end to the other

81:14 And you're good to go that one two too too. How do you

81:24 good. I got your emails. . Maybe. Let me see.

81:36 trying to remember. What am I at? I look at a calendar

81:38 Monday next week I want that. want that. I'm going to be

81:46 a committee meeting all day long. . Mhm. Friday. This Friday

81:58 think so. What time there? in my office? I work.

82:09 right. I'm, I'm putting it . Ok. Actually I'm gonna put

82:13 over here. How was today? huh. Yes. Like, like

82:18 types of alcohol that are good

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