Renal

So the kidneys are called retroperitoneal organs. So they're actually not surrounded by the peritoneal membranes. They're actually found behind them. So kind of interesting. The ovaries are retroperitoneal organs as well. Just a little bit of an aside. But if we look in the abdominal cavity. So we can see these paired organs, the kidneys. One of them is, the right one is just shifted down a little bit. relative to the left one. And the reason for that is there's this huge organ sitting here called the what? liver. Now sitting on top of the kidneys, you know all about these, right? Those are the suprarenal glands. Also known as the adrenal glands. So you see those. And what they don't show here is there'd be a nice pad of fat that is surrounding the kidneys too. So all Oregon's got a nice cushion of adipose tissue. we have an indentation of the kidney on the medial face. That indentation there is called a hillus or a hilum. We talked about the Highlands or the Hillises, if you will, of the lungs before. So these are the indentations on the medial face of the kidney. And what we find there are two really important vessels and then we find a muscular tube. So the two important vessels are the renal artery and the renal vein. So if you look at the abdominal aorta, it's got this huge vessel that comes off it. that is called the celiac trunk that's feeding the GI. And then it's got these huge vessels that come off and go to your kidneys, the renal arteries. And of course, the renal veins are bringing venous blood back into your inferior vena cava. Now, also in that Hillam region, we actually have this big muscular tube coming out there. These are called the ureters. And they do peristaltic contractions, even though gravity is helping urine move here. So urine that was created by the kidneys is traveling down these tubes. And these tubes open up into the urinary bladder located right here. Now, if we blow up the bladder what we see is there's no tubes that just open up into the top of it. So in other words, the ureters don't open up into the top of the bladder. It might look like that from this image. But if you go down here there's an opening right here. What that means is these tubes run behind a bladder and they open up into the bottom of it And that forms two openings there, just almost into the floor of the bladder they open into it. And then there's another opening coming out of the floor of the bladder that goes into your urethra. So the urethra is the final exit point for urine. Now, there's smooth muscle right here that regulates that opening regulates that opening It's a sphincter. We call it the internal urethral sphincter. And then on the outside of that, we have skeletal muscle So we have volitional control over when we want to urinate or not as well. So this is the gross anatomy of a kidney. And so… This is an image on the left. So it's just an artist rendition of an actual kidney that you see on the right. And when you caught a kidney in cross section and you take a look at it, this would actually be longitudinal section. I guess it depends on the way you want to look at the kidney. It could be a cross-section as well. So you don't really see all that much. I mean, there's some interesting structures there, but not as much detail you would see with like cutting a heart open or something like that. What we notice with most organs is that there is a cortex on the outside and a medulla on the inside. So here's the cortical tissue of the kidney. This is the medullary tissue of the kidney. So nicely in the image to the left in purple, they have what the medulla of the kidney is. And this light stuff out here, that would be all cortex Now, what's interesting is we can actually see that with an actual kidney we slice open without even using any stain. You can see this is all cortical tissue here. And then this dark stuff, that's all medullary tissue. So that's the medulla. of the kidney. Now, more specifically then, what we can say is that the medulla of the kidney is made up of what we call renal pyramids. So these renal pyramids are these triangular shaped structures. And there's about, I don't know, 10 or 12 of these per kidney, these renal pyramids. Now, you might look at this image and say, well, I don't count 10 or 12. One, two, three, four, five, six, seven. The reason for that is the reason for that This is a two-dimensional slice. So there could be renal pyramids on this side of the screen. There could be renal pyramids inside the screen as well, right? It's a three-dimensional organ. We're just looking too deep. So about 10 to 12 of these. the base of the renal pyramid bases, the cortex of the kidney The apex of the renal pyramid sorry faces what we call the pelvis of the kidney This is the pelvis right here. Now, what you can see is the cortical tissue actually dips between the renal pyramids. We call them renal columns. So that's a renal column here. That's a renal column here, another one here. And I think walking into this class, your general understanding of the function of the kidney would probably be to filter our blood and get rid of waste. Would you agree with that? We'll talk about some other functions as well. Those cortical columns there, they don't really have any function in that. There's a lot of blood vessels there. There's a lot of connective tissue there, but the cortical columns don't really do what this cortex up here does. So even though that this is part of cortical tissue, it's different than this cortical tissue up here. And I'll talk about that more a little bit later. Now, basically what we're doing in the kidney is, as you suspected, is we're basically filtering blood And we're filtering out organic waste and we're forming urine. And that's going to happen in this kind of process here in this direction. So it's going to start up here in the cortex. It's going to move its way down the medulla. and eventually urine is going to drip. into those little spaces. So we have this kind of little network of tubules that are in this hilum region of the kidney And those little tubules are called minor calyces. Nice and quiet in here, isn't it? I like this. I like it. So we have these minor calyces. So we got some urine dripping into these. And then what's going to happen is many minor calyces are going to fuse together to form one huge Major Caliphs. And then we have a few major calyces that open up into this. pelvis. And then the pelvis opens up into your ureter. The pelvis undergoes peristaltic contractions and so do the ureters repelling urine down the tubular system. And again, gravity is going to help that. Now you can see from this particular image, there's an opening here to a minor calyx. So there must be in the screen another renal pyramid, right? Now, on the image to the right, what you can see is a couple of things that are kind of cool. You can see now the renal artery and the renal vein. So renal artery much smaller in diameter, renal vein, much bigger. And again, you see the muscular ureter there. Questions on this? Okay, so now the question is, is this. What makes up this tissue So literally what makes up the medullary tissue, what makes up the cortical tissue? What is the kidney made up of? Well, clearly I'd mentioned blood vessels, so there's a lot of blood vessels there. But what's doing all the filtering? The answer is these structures that are called nephrons. How many people have heard of a nephron? Most of you have. Good. So that's how the nephrons would look in orientation in the kidney. It's a gross exaggeration because There's about a million nephrons per kidney. But this is the orientation that they would have. Obviously, they wouldn't look that big relative to this kidney. Now, note this line here. This is the separation between the cortex and the medulla. The cortex above, the medulla below. So let's look at the nephron. Let's talk about the pieces and parts of it. And then we'll talk about what parts of it are found in the cortex, what parts are found in the medulla. So the beginning of the nephron is this structure right here. that is called Bowman's Capsule. And this is a three-dimensional sphere that's got two openings to it. So Bowman's capsule is a three-dimensional sphere. It's lined by a simple squamous epithelium It's got an opening here that we call a vascular pole. And it's got an opening here that we call a urinary pole. whole meaning like, you know, equator or something like that, North Pole, South Pole. So we have this one pole that is the vascular pole because blood vessels come in and out of that opening. And then we have a urinary pole because that's where we're starting to form Urine. Now, inside Bowman's capsule is the only place in the human body where we find fenestrated capillaries. So that fenestrated capillary network right there is called a glomerulus. So the glomerulus is found inside Bowman's capsule. And you can see that Bowman's capsule's got a double layer of cells. It's got an inside layer we call a visceral layer. And it's got this outside parietal one. So we'll talk about that later, the parietal and visceral layers of Bowman's capsule. And then obviously there's a space between the two. And we call that Bowman Space. Now, collectively, this whole thing right here is called a renal corpusole. So let me say that again. We have Bowman's capsule with a fenestrated capillary network on the inside called a glomerulus, those two together we call a renal corpusal. Now, Bowman's capsule at the urinary pole is going to open up into this tubular network. So think about it as this long straw that is just convoluted. And the straw is lined by simple epithelium. Most of it is simple cuboidal epithelium. And so you can see that here, Bowman's capsule opens up into this tubule that is called the proximal convoluted tubule. Most people just say PCT. So it's proximal, meaning that it's closest to the point of attachment to Bowman's capsule. That's what we mean by proximal. And clearly you can see that it's convoluted. So we have the proximal convoluted tubule. And then what happens is that descends down into the medulla as the descending limb of the loop of Henle. So that's the descending limb of loop of Henle. Now that epithelium is a little bit thinner. It's a simple squamous, but we'll get back to that in a little bit. And then with the loop of Henle forms this hairpin turn And now we have the ascending limb of loop of Henle. And there's a portion of that that's thin, but there's also a portion of it that's really important that's thick. We call it the TAL. So this right here is called the thick ascending limb. The thick ascending limb is really, really important. We'll talk about it later. So now we've moved back up to the cortex. And then we open up into the distal convoluted tubule. So we often call that DCT. Distal meaning more distal from the point of attachment to the Bowman's capsule. Obviously, it's very close to Bowman's capsule We're talking about physical attachment to Bowman's capsule. So it's quite far away in that regard. And so we have the DCT there. That's quite convoluted as well as you can see. Now, what happens is several of these nephrons are going to share a common what we call collecting duct. Here they call it collecting tubule, just call it a collecting duct. And what happens is the way that they connect to a collecting duct collectively is via these connecting tubules. So that's a connecting tubule, another one, another one, another one. And this is right here. This nephron has a connecting tubule connecting it to the collecting duct, which is this huge tube here. Now, that huge tube there is right here, people. And that huge tube is opening up into the renal papilla. So if you go back to the previous slide. the tip or the apex of a renal pyramid is called a renal papilla. The pillow means like finger-like. And you can see a bunch of collecting ducts are forming this like diaphragm like structure And that's where urine is going to drip out of. into where? urine drips out of a renal papilla into what? I'm sorry? Not the ureter that's further down. Yeah, minor calyx. So it'll dump into a minor calyx and then again, major calyx and then the ureter and then or pelvis and then uricula. So now, if you had to go back and say, well, what do we find in the cortex and what do we find in the medulla? Well, in the cortex we find in the cortex renal corpuscles, PCTs, and DCTs. What do we find in the medulla? We find loops of Henle and collecting ducts. Now, if you look at this, you could clearly say, well, there's portions of the collecting duct that are in the cortex. There's portions of the loops of Henley that are located in the cortex as well. That's all fine and dandy. But in general, and the way I'll examine you. And if you take a histology course, they'll do the same. We find Bowman's capsules in the glomeruli, which are collectively called renal corpusils. PCTs and DCTs, that stuff is in the cortex. In the medulla, we find loops of Henle and collecting ducts. And you can see that clearly. Right here. I was just talking to Brock before class. And he's like totally stressed out. He just did an interview Friday. And he's hoping to get into PD school so i'm assuming That's what that phone call is for. Did he just like run out there? Yeah. I'm sorry? Yeah, we will ask him when he comes back. Because if that's not why, we got to ask him why he walked out of class. If it's bad. It's an illegal movement. Yeah, the question is, if it's bad, does he come back? So it's actually his hometown. So he's really excited about going there. Okay. So here's a look at the kidney on the left. And what I really like about this image is it takes the nephron and it shows the nephron in its orientation in the kidney. So again, exaggeration, right? The nephron is quite large relative to the side of the kidney. size of the kidney. There's a million of these. per nephron, sorry, per kidney, these nephrons But the orientation is good again Bowman's capsules, PCTs, DCTs in the cortex, the medulla, loop of Henle, and collecting ducts. Now, what you can also see is those renal columns that I was talking about, like here, here, here. a lot of vasculature there. A lot of connective tissue there. So we're not really doing anything other than like pretty much allowing blood flow to go through there. Not much filtering of blood and stuff like that going on. It's more of like kind of these passageways for vasculature. Now off to the right is how a kidney would, sorry, a nephron would actually look. So when we look at this nephron, it's very simplistic. A lot of people draw nephrons like this. And it's very simplistic looking and that's good because it helps us understand it. But the reality is the nephron looks like this. Sorry. ECT. D-C-T. So it looks more like that. There's your glomerulus there. In other words, the renal corpuscle is pointed back at the distal convoluted tubule. So it's not pointed away from it. And you can see that here. So this is the renal corpuscle. That's Bowman's capsule plus the glomerulus inside of it. You can see it's actually facing the vascular pole is facing distal convoluted tubule. And that's really important anatomically speaking and physiological speaking. Because cells in that area between the vascular pull and the distal convoluted tubule, they work together to form that juxtaglomerular apparatus. Remember me mentioning that before? JG apparatus. that's where that's going on here. Okay, so now we see… proximal convoluted tubule here. And there's our descending limb of loop of Henle. ascending limb of loop of Henley. And then there's our DCT into a connecting tubule or collecting tubule into the collecting duct. Now, again, one of the reasons why I think you should take iBio 408 is because you look at this and you say, well, yeah, that's cool. I can kind of see how it works. In that class, you have to look at it like this. and understand what PCT is, DCT is, what's loop of Henley, all that stuff. And that's really cool. So you have to imagine something that you know what it looks like in 3D, what would it look like in 2D? And vice versa, right? You have to look at this under a scope and picture how that would be in 3D. In other words, you'd have to picture that this DCT is probably coming out of the screen and then going into that one. And that one's going into the screen and maybe coming out as that one. it's just a 2D slice through this, so you're not going to be able to see Sometimes you'll see lengths of tubes if you get a good slice. Normally you don't. You just see it like this. Now, as I said, most of this is cuboidal epithelium, so proximal convoluted tubule distal convoluted tubule or cuboidal epithelial cells They're kind of like cubes, just as tall as they are wide the loop of Henle is actually a simple squamous. It's really thin. We actually want to reabsorb some water there, so we want it to be thin. The collecting duct is usually a columnar epithelium, so it's a little bit taller. And then the ascending limb loop of Hindle, more specifically the thick ascending limb. We call it thick because it's cuboidal instead of squamous. And congratulations. Congratulations, brother. Thank you. He's going home. Even though the lions destroyed the Colts. Okay. So this is a image right here on the left of the cortex of the kidney and check this out here. These… our renal corpuscles. So if you look really closely, that is the glomerulus there and that little white space is Bowman's capsule. Now, what you're also seeing there are some tubes and some of them you actually see a little bit the length of the tube. And you're seeing a lot of circles as well. And if you blow it up, it looks like this. So here's distal convoluted tubule, proximal convoluted tubule. Things like that. Again, another reason I think you should take iBio 408 is because By the way, I have no connection with this class i just know that histology is important for you. How many people are pre-PA? Don't take that class. Pre-dent, take it. Big time taken. Remed, take it. Nursing, don't take it. And what I mean by that is those curricula, nursing and PA, they don't have any histology in it. Dental school, medical school, huge. Huge, a lot of histology in it. So look, here's something really cool. Check this out. you don't even know about the physiology of the nephron yet, but you're going to learn it just by looking at the histology Look at the proximal convoluted tubule. Here's the cellular apical surface And what you can see is there's some wispy things That's what my… the woman that taught me everything that I know about really pretty much everything biology. She called them wispy things. So I don't know if that's a word or not. Is it? these little wispy things, they're microvilli. And those microvilli are a brush border. We talked about the brush border before in the small intestine. What is a brush border there for? What are microvilli there for? Crease surface area for what? absorption. So now you've learned something. What does the proximal convoluted tubule do? It reabsorbs Solute. So when you're filtering blood out of Bowman's capsule into PCT, The primary function of PCT is to reabsorb stuff. Now, you might say to yourself, sounds kind of like ridiculous because if we just filtered all this stuff, why do we want to reabsorb it? We'll get to that in a little bit. Look at the DCT. Do you see a brush border? It's not involved in that. So does it do a little bit of absorption? Yeah, but not much. And so now you know that the DCT is more involved in secreting things. PCT is more involved in reabsorbing things. And you haven't even learned about the physiology yet. So the anatomy allows you to predict the physiology and vice versa is true as well. So if you go to lecture and you learn about PCT and DCT and what they do, when you go to lab, you know what to look for. You know, to look for the tubes that got the microvilli, if you're looking for PCTs. So it's really cool. This is renal medulla here. I'm not too sure how much this is medulla here because I see some PCTs here. So I wouldn't really worry about that, but this certainly is. Look at this here. Simple cuboidal epithelium. That's a thick ascending limb. Simple cuboidal here, simple cuboidal. That's the lumen, by the way, here, here. Look at this bad boy right here. Look at that. Here's what that is. One epithelial cell. two epithelial cells. That's a loop of Henley right there. just two epithelial cells make up the entire wall of that actual tube. Another one down there. another loop of Henley. Could be thin ascending limb, could be the hairpin down at the bottom. Cool? Not really? None of these images on the test. Don't worry about that. So we have two different types of nephrons in the kidney. We have cortical nephrons and we have juxtamedullary nephrons. Cortical nephrons make up like, I don't know. let's just run with 80%. It's a little bit higher than that, but we'll run with 80%. So 80% of all nephrons are cortical and about 20% are juxtamedullary nephrons. So 80% of them do what you thought the kidney does before you walk into this class. So you said, hey, the kidney filters blood and forms urine. That's what cortical nephrons do. And it makes sense that 80% of our nephrons are that. The juxtamedular nephrons, they do some of that too, but they're really involved in something else. They're involved in creating a lot of solute in your medullary interstitium. So the ISF. of the medulla. There's a lot of salt there and there's a lot of urea there. And we need that solute concentration there outside the tubules. It's that long loop of Henle of the juxtamedullary nephron that does that. it creates that osmotic gradient. And it's really important if we want to regulate Water balance. But they filter a little bit of blood as well. And you can see these collecting ducts opening up into the renal papilla, which opens up into a minor calyx. Then Major Calyx, then pelvis, then ureters. Now, they call the cortical nephron a cortical nephron because it's almost entirely located in the cortex. They call the juxtamedullary nephron such because juxta means next to So this nephron is kind of like shifted towards the medulla. Even though the renal corpuscle is still in the cortex. You don't find renal corpuscles and medulla. Never. And as a matter of fact, you don't even find renal corpusils in renal columns. So renal columns, even though they're cortical tissue, we don't find renal corpus there. So this is renal vasculature here. The renal artery is huge coming off the aorta, by the way. And so here's the renal artery coming into the hilum. And it first forms a segmental artery And then the segmental artery, that'll run in the renal column regions. We call that the interlob, sorry, interlobar artery. So much of that is interlobar arteries and veins that are cruising through the renal columns. And then once you get out to the base. of the renal pyramid, there's kind of like this little arc of a blood vessel and it's kind of like aptly named. It's called arcuate artery. So the arcuate artery kind of like wraps around the base of the renal pyramid And then this interlobular one just shoots like straight out towards the cortex And what it feeds is the glomerulus and the portion of it is the afferent arteriole. So the interlobular artery becomes the afferent arterial. That's what delivers blood into the glomerulus. And then what delivers blood out of the glomerulus is the efferent arteriole. So it sort of looks like this. Here's Bowman's capsule. There's your glomerulus. there's a blood vessel that comes in, afferent arterial. there's a blood vessel that comes out efferent arterial. So you can look at it like the afferent arteriole forms the glomerulus I don't know if it does. And then the efferent arterial drains it. I would just look at it like afferent arterial brings blood to the glomerulus. deeper and arterial drains blood out of it. Now, a lot of people like to call this a portal system, but it's not by definition because by definition, a portal system is where you have a venus Sorry, where you have a capillary bed that drains to another capillary bed through what? So you got an artery that feeds a capillary bed arterial, feeds a capillary bed But then instead of that capillary bed draining into venules and back to the heart. that capillary bed drains in the venules and drains into another capillary bed, right? And then goes in the venules and then goes back to the heart. That's a true portal system. In other words, what's separating the two capillary beds are venules. It's not the case here. This is so unique. It's the only place that exists in the human body. Here, the glomerulus has a resistance vessel on each side of it. So it's got an afferent arteriole that can vasodilate, vasoconstrict. And it's got an efferent arteriole that can vasodilate, vasoconstrict. Now, indeed, you are going to leave here and go to a capillary system Which I can see how they kind of consider that. a portal system, but it's not true in a sense of the fact that it's an arterial feeding that. Okay, so now you can see that the efferent arteriole, when it comes out, here it is, sorry. Here's the efferent arteriole right here. When it comes out, it feeds this. That's your peritubular capillaries. So peri means surrounding. We have capillaries surrounding the nephron, surrounding the PCT, the DCT, surrounding the loop of Henle. We call this the peritubular capillary network. they don't show it here surrounding this loop at henley but There's some that does. There's just not a lot. Now, if you look at the juxtamedullary nephron. They got peritubular capillaries up here. But also down here as well. Now, it's kind of weird here because it's kind of weird I think a lot of people just give the name to the capillaries that surround the loop of Henle. of the juxtamedullary nephron then they don't go back to point out that they're just simply peritubular capillaries. So my point is this. These capillaries that surround the loop of Henle, the really long loop of Henle of the juxtamedullary nephron. They're called the vasorecta. But what I want to say to you is they're nothing more than peritubular capillaries. They're just special peritubular capillaries that surround the loop of Henley of juxtamedullary nephrons. And we'll talk about their special function in a little bit. So then these peritubular capillaries will drain into the interlobular vein arcuate, interlobar. just the reverse of the arterial circulation go to the renal vein that goes through the inferior vena cava. Now, hopefully what comes back from the vein into circulation is going to be Good stuff. So the stuff that we didn't want to lose, like red blood cells, white blood cells, platelets albumin, stuff like that. That stuff we didn't want to lose with filtration. And generally speaking, we won't lose that stuff. So one thing I want to point out before moving on is I want to go back to the slide really quick here. And I want to point out Take a look at the juxtamedullary nephron and look at how much it pretty much traverses the entire length of the medulla. So it pretty much spans the entire length of the medulla. These are really, really, really long loops of Henle. And the reason for that is you want to concentrate this medullary tissue all the way throughout And what I mean by the medullary tissue, again, is the interstitial tissue between the nephron tubules. Notably, the collecting ducts and the loops of Henley. So here's your afferent arterial. Here's your efferent arteriole. there's your peritubular capillaries. That's of a cortical nephron. Look at the juxtamagullary. Well, it's the same But we call these peritubular capillaries vasorecta. Great. There's still peritubular capillaries. So let me point out something to you really important. The afferent arteriole is bringing in all of your blood to your nephrons. So, I mean, everything in your plasma, everything in your blood is going there. And what's going to happen at the level of the glomerulus is we're going to filter into here. We're going to filter our blood into Bowman space. Now, look, what we want to get rid of is largely organic waste. like urea, uric acid, creatinine. I told you the human body can't really handle nitrogenous waste, not really good at metabolizing them. So it just excretes those. So that's the things we want to get rid of. So you would think that's just the stuff that we filter. But interestingly, the way that the filtration apparatus is set up is it only filters based on size and charge. And really the more important of the two is size. And the way that it works is that it works really only allows things that are small enough to be dissolved in plasma to be filtered and everything else stays behind. So in other words, when this blood comes in the afferent arteriole, what do we filter into Bowman's capsule or Bowman space? Well, the things that go into there are things like glucose, amino acids. vitamins, minerals. ions you know electrolytes, stuff like that So think about it. We just talked about the digestive system. And all of this good stuff like amino acids and carbohydrates and all that stuff. All this stuff we just digested that we want for ourselves, I'm telling you right now that we're filtering it all into Bowman's capsule Now, things that are not filtered that are too large are things like red blood cells, white blood cells, platelets, albumin, stuff like that. That stuff stays behind. And what also goes along with amino acids and all that stuff, which is all good stuff, is the bad stuff too. The urea, the uric acid, the creatinine, and that junk. And maybe some drugs and toxicants and things like that. So there's a lot of good and bad stuff being dumped. Now, if you follow the nephron. If we're in here now in Bowman's capsule. Or more specifically, we're in bowman space There's good stuff there. Let's say glucose and amino acids. Where's that stuff heading? Well, it's going to go along the PCT. descending limb of loop of Henle. ascending limb loop of Henley. DCT. collecting duct. Minor calyx, major calyx. pelvis, ureter. urinary bladder, urethra. Then what? toilet, right? So it's going to the toilet. So just think about that for a second. We just talked about an entire lecture about how we painstakingly digested food So that we could absorb it and get it into our bloodstream, right? And now I'm telling you, once that stuff circulates through the kidney. By the way, we just don't like direct it to the kidney. It just happens to be going there. there's blood going to the kidney to keep it alive too. But when it goes through the kidney, it gets filtered. And the kidney doesn't filter based on whether you're good or bad. filters based on basically size through the good and bad stuff go. So I'm telling you at some point hanging out in your nephron on its way to the toilet is amino acids. monosaccharides, electrolytes. all this good stuff that we want. And quite frankly, a lot of water that we don't want to lose because the water is the vector for the things to be dissolved in. But check this out. That's why we have an efferent arterial. So the efferent arteriole forms these peritubular capillaries that surround the nephron And what they do is they give you an opportunity here at the PCT. Hey, if there's something in here that you want and you don't want in the toilet. Put it here. And they tell you right here at the DCT, if there's something maybe you wanted to get rid of that you didn't with filtration. Put it there. So that's why the peritubular capillaries are there so that we can communicate with that tube along the way And we can reabsorb the good stuff and maybe dump some more bad stuff So at the end of the day, we're not getting rid of glucose amino acids and electrolytes and stuff like that. So that's the purpose of the peritubular capillary network. Now, don't forget that both of these are resistance vessels. So we can vasodilate, vasoconstrict, afferent and efferent arterioles. And that helps us regulate the pressure at which we're doing this, at which we're filtering blood. So here are the basic renal processes. One is filtration. So we're filtering things like water electrolytes organic nutrients Again, good stuff, but also waste as well. we're reabsorbing water, electrolytes, organic nutrients. So all the good stuff we reabsorb. And again, you might say, why do we do this? Why do we filter all the good stuff yet to just reabsorb it? Just because the filtration apparatus is largely based on size. that quality of substance, if you will. We also secrete things, so electrolytes drugs like antibiotics, toxicants like nicotine, that stuff's dumped at the level of the kidney. And then we excrete. And what we excrete is organic metabolic waste. And again, these are nitrogenous wastes So urea from protein metabolism uric acid from nucleic acid metabolism And then creatinine from creatine. metabolism. And then with the kidney, we also do a lot of regulation. So we regulate our plasma pH. Is that minute-to-minute basis or chronic? Yeah, chronic. So the kidney would be chronic, respiration would be minute to minute. plasma electrolyte levels, blood volume, blood pressure. calcium homeostasis. We talked about this, what hormone influences it at the level of the kidney? And we talked about endocrine. when hormone is working on the kidney to help regulate calcium. Very good. PTH, parathyroid hormone. Okay, so here we have some… solute that's coming in from the afferent arterial going into Bowman's capsule. And we're filtering it. So I keep talking about Bowman Space. This is it right there. Bowman Space, Bowman's capsular space, any of that is fine. And that stuff is accumulating there. And again, this is vascular pull. This is urinary pole. So that stuff's being dumped here into proximal convoluted tubule. Now, we call this fluid tubular fluid. We call this peritubular fluid, which is nothing more than ISF. And we call this IVF. or plasma. Those intravascular fluid or plasma. So the first process is filtration. The only place we do that in the nephron is at the level of Bowman's capsule with the glomerulus Because that's a fenestrated capillary network. It's not continuous capillaries. It's not sinusoidal capillaries. It's fenestrated capillaries. The ones with the little windows, if you will, the little holes in the plasma membrane. So now what we can do is we can reabsorb stuff. So that stuff we didn't want to lose, we can reabsorb it. And so by definition, the way you want to look at this is you want to say something is moving from the tubular fluid to the peritubular fluid And then from the peritubular fluid back to the bloodstream. So I know it would be simple to say, well, we just reabsorb it right into the blood, but that's not necessarily always the case. So some things are reabsorbed and just kind of like chill in the peritubular space. And then many other things will go from the peritubular space then into the blood as well. So remember when I was talking about the juxtamedular nephron in that long loop of Henle. we reabsorb salt and it just hangs out there in the medullary space instead of being picked up by the bloodstream. And then what we can do is we can dump some stuff that we didn't do with filtration. So kind of like a backup process to filtration, we can take some stuff here largely it's in the distal convoluted tubule And we can dump that stuff. from, again, the vascular fluid to the peritubular fluid. to the tubular fluid so that would be secretion. Finally, we excrete. So the only circumstance of excretion would be actually actually removing urine from the body during urination. So again, we talked about this with GI. excretion and secretion are not synonymous. Okay, this is a cool cartoon. I really like it a lot. It's pretty descriptive. I need to create just a better resolution one someday. But here is your glomerulus. And you can see that there's a bunch of junk in here. So some protein. I think there's like an apple in here, all kinds of stuff. And there's your filtration membrane, which we'll talk about in a little bit. But basically, here's all the stuff now we're filtering into Bowman space We call that at that point glomerular filtrate. That's what we call it. We don't call it urine yet. We call it glomerular filtrate. Now, remember, there's good stuff and bad stuff there. And what happens is it then goes into the proximal convoluted tubule So this is PCT right here. And there's a couple guys there. One of them's got a fishing net and the other one's got this beaker here that He's dumping some stuff there. So what they're trying to say is with the fishing net, we're reabsorbing stuff. And with the beaker, we're dumping some stuff. So we're secreting some stuff. Now, largely speaking at the PCT, we don't secrete much. We do a little bit. It might be like a little bit bicarb ion or it might be proton or something like that. So I don't want to say it doesn't happen, but largely what happens here is what I want you to know we reabsorb here. That's the big deal that's happening here. And by the way, you know this. You don't have to take my word for it. proximal convoluted tubule cells have microvilli distal convoluted tubule cells don't. So we're doing reabsorption here largely. Now, things that we're reabsorbing are like water glucose, vitamins, amino acids, stuff like that. So electrolytes, all kinds of good stuff. that we didn't want to lose. Things were letting go by urea, uric acid, creatinine. Now, how do we do that? Well, we have proteins in the membrane of the PCT that select for the things we want to take back into our bloodstream. So now this is a selective process of reabsorption whereas filtration wasn't very selective, right? It was only selective based on size. So then we go down the descending limb of loop of Henle, and you can see here we're reabsorbing water. And so we reabsorbed water here, but now we're reabsorbing a little bit more water here. But the only reason we're reabsorbing in here, really, there's two reasons. One is the epithelium is really thin, so it's a simple squamous epithelium. Two, is there's an osmotic gradient for it. Now, the question is, why is the osmotic gradient there? Well, something put all this salt out here. something created all this salt in this medullary tissue How do I get rid of that? I'm just going to get out of that. So something is creating all that salt in that medullary tissue of the kidney that is creating that osmotic gradient So that we can reabsorb this stuff. And we're going to get to that in a second what that is. So now when you reabsorb this water, look what happens to your filtrate. So your filtrate's not very concentrated here. So again, we call it glomerular filtrate at this point. But now it's really concentrated in that hairpin of the loop of Henley. Well, it's really concentrated because you've been removing water from it. And then what happens is that as it turns the hairpin and it goes up the ascending limb. here's this guy here and they say that he's running these salt pumps And this is a big I just think confusion in science and it's not by scientists, but it's by people that teach this stuff that call these things pumps. They're not pumps. These are secondary active transporters. We'll look at them in detail in a second. So nothing's pumping anything out, but by secondary active transport, that's what's moving the salt out here. So all this salt that is in your tubule, it's being moved out here by this guy. a secondary active transport. So what's concentrating all this medullary tissue assault I mean, I know my arrows look like the salt's just going here, but it's going everywhere. This guy's throwing salt everywhere, right? Look at him. He looks crazy. He's going nuts there, just moving all the salt out. The salt is all over the place. And again, it creates the osmotic gradient for things to move towards that area. So that is in the thick ascending limb, by the way, where this guy's hanging out. So the thick ascending limb, the reason why I said it's so important is that's where these secondary active transporters are working. reabsorbing salt. Now think about that. If we think reabsorbing salt, we think, okay, we're reabsorbing it into our blood. No, we're reabsorbing it just here into the peritubular fluid. Just hanging out here. Now, the question is, why does it stay there? Why doesn't it go into our blood? The answer is actually it does go in our blood and then our blood puts it right back there. And we'll see why in a little bit. So now we go up here and we're back to roughly the same concentration as we were. In the PCT, And then we got these guys hanging out here again. So we reabsorb very little. And you know we don't reabsorb much because there's no microvilli here. So we reabsorb a little bit like maybe bicarb proton relatives who are pH. But we secrete things here. So we often look as a DCT as a backup to filtration. So things that you wanted to filter that you didn't filter, you can hear like drugs and toxicants and things like that, we can dump selectively here. at the level of the distal convoluted tubule. There's your connecting tubule. Now we're in the collecting duct. And now, if… Big if. If ADH is present, and you guys know all about ADH, If ADH is present, we'll reabsorb some more water here as well. Now, normally ADH is not present. So normally it's not secreted. It's not tonically secreted. So for now, we can just get rid of these arrows. And we can say, well, we've just formed this urine now. This urine is pretty voluminous. It's a large volume. It's relatively dilute. You got normal urine, it's usually like clearish in color, maybe a little tinge of yellow. So large volume urine, very dilute is very normal. Now, if we're losing a lot of water from the body. Or if we're trying to regulate blood pressure, it's too low. Then what we might do is allow this. And we do that by ADH. ADH will cause the collecting duct to cause a reabsorption of water. But we'll get back to when that circumstance would exist. But normally, ADH is not there and we don't reabsorb water at the collecting duct. Let me point out one last thing, and I'll point it out again on another slide. The descending limb to loop of Henle is permeable to water but not solute. You don't have to write it down because it's actually coming up on a slide. But the descending limb is permeable to water but not solute. The ascending limb is permeable to solute but not water. The collecting duct is normally not permeable to water. but is under ADH hormonal stimulation. Questions? Yes. Yeah. And I like the way you worded it. So yeah, only the thick ascending limb has those salt transporters. Yes. Yeah, definitely. So the question is, do the juxtamedular nephrons have more of these salt transporters than cortical? Yeah. And quite honestly, I don't know if the cortical ones even have them But they probably do. But the expression is much higher in chunks of medullary. Cortical nephrons are not responsible for concentrating medullary tissue. Okay, so here's Bowman's capsule. You've already learned about this. You know that Bowman's capsule plus the glomerulus inside of it is called the renal corpus. So there's how that looks. So it's got two layers to it. This outer layer is a simple squamous epithelium. We call that the parietal layer. And then look at the visceral layer. It's weird. So it's got these cells that are called podocytes that form these little finger-like projections that are called pedestals. So here's a podocyte nucleus here And there's its finger-like projections that are called pedestals What cells did we see like this before anatomically speaking? and the blood-brain barrier, what cells astrocytes, right? Astrocytes form pedestals as well. Different function here. These pedestals are kind of lining up like your fingers against one another. and you spread your fingers a little bit and you create these slits between them. That's what's going on here. So we're creating what we call these filtration slits which is contributing to the selectivity barrier of the glomerular filtration membrane, which again, just largely selects based on size, but also charge as well. So the visceral layer of Bowman's capsule is quite weird looking, right? It's these anastomosing looking cells that are called podocytes with pedestals. There's your afferent arterial, there's your efferent arterial afferent is always larger than the efferent in case you care. I won't ask you on the exam, but you might see that later. And then you can see smooth muscle cells of the afferent arteriole Which we would expect. Eferent has them as well. But when you get closer here to the vascular pole, some of these smooth muscle cells here they change into these cells. So the smooth muscle cells become JG cells. So we say that modified smooth muscle cells of the afferent arteriole become juxtaglomerular cells. Let me say that again. modified smooth muscle cells of the afferent arteriole become juxtaglomerular cells now With blood, we talked about JG cells being responsive Did we say in a mechanosensitive fashion or a chemosensitive fashion? in the context of polycythemia. Yes. Not chemo. Actually, I take that back. You're correct. Yeah, it is chemo, right? So when they sense low oxygen, maybe if you're up in high altitude. What do they spit out? They don't spit out red blood cells. They don't spend on hemoglobin. What do they spit out EPO. So they spit out EPO. And then EPO goes to your bone marrow, makes you make more red blood cells, and now you increase the surface area to bind oxygen that's limited in the atmosphere. So thank you indeed. chemoreceptive cells. These cells are also baroreceptive, which we're going to see shortly. If they sense low pressure going to the kidney. They actually respond by spitting out a different hormone that's called renin. You don't have to write that down now. It's coming up later. So really cool cells, these modified smooth muscle cells of the afferent arteriole. Now, the JAG apparatus, the juxtalglomerular apparatus, is a little bit more complex than that, but it's above scope of this class. So it not only includes those JG cells, but also cells of the distal convoluted tubule that are called macula densa cells And then these cells between them that are called the mesangial cells. Don't worry about those. I won't ask you about them. But it's really like complex. So in other words The kidney can sense what's happening in your blood to regulate afferent efferent arterial vasodilation, vasoconstriction. But it also can sound to what's going on in your nephron. Because it's sensing via the distal convoluted tubules what's going on as well. Again, that's pretty complex for this class. Don't worry about that. Just know JG cells are both chemoreceptive And we'll talk about the mechanoreceptive nature of it shortly. look at your PCT really nice with microvilli there. And by the way, that's why I keep saying that that's the proper way to look at an Ephron. Everyone you see will draw it on the board like this. And again, that's fine for simplicity purposes, but you have to take this and you have to pivot at 180 if you want it correct. And the reason you want it correct is so that you can form the JG apparatus. I'm sorry. And stuff like glucose in the environment. Yeah, so I'll answer. Give me one second. I'll answer coming up. It's a great question. So the question is, what happens to individuals that have diabetes that end up with glucose in their urine. We'll talk about that. All right. So I'm trying to convince you to take iBio 408. Is that gorgeous? Yeah, kind of. Check this out. That's a glomerulus. there's Bowman's space of Bowman's capsule. What's that right there? proximal convoluted tubule, all that little wispy stuff is microbella. This is all PCT here. That's DCT right there. That's a little arterial right there. Not sure here. Probably DCT. No one fancies that image. So the glomerular filtration membrane is made up of a capillary endothelium. just typical endothelium. Well, I take that back. Not a typical endothelium fenestrated capillary endothelium, which is quite unique. basement membrane, which is basically a mat of protein that sits beneath a single layer of cells. And then those podocyte pedestals. So if we blow this up and take a look at it. Here we can see these endothelial cells. And what we can see here is holes in the membrane. Now, I know this looks like gaps between endothelial cells But these are actually holes in the plasma membrane. So kind of like aquaporins, if you will, but not like aquaporins but they are literally pours right through the plasma membrane that allow the movement of solutes through that. Question over there? I may help. None, I can help. And so what we want to do under pressure is we want to push solutes Like that. We want to push it from the blood vessel through those little holes, which is not much of a problem. We want to push it through this mat of protein, which is not much of a problem. And then we want to push it between these Not sure why. It's like a bigger issue than a bigger issue Let's take a break. By the way, that wasn't my computer. The computer crashed. Another acceptance. Okay, so again, we want to filter things out of the glomerulus through these fenestry Again, I know this looks like gaps between endothelial cells, but check this out. they only show one nucleus here. So this is all one endothelial cell that's got pores in its membrane. through this mat of protein, which is a couple basement membranes. And then between these filtration slits. So these are the pedestals of the podocytes. Now, if you look at these pedestals, it's actually really cool You look at one pedestal and you look at another pedestal here, they actually have integral membrane proteins that have these extracellular moieties that kind of connect to each other. And so it's not as simple as going through that little slit as well. You got to go through like this meshwork of protein as well. And that's got a lot of negative charges that repel things that are negatively charged. So we call this the filtration slit diaphragm. And that's really cool because these proteins are like called nephrons Or sorry, nephrins that are integral membrane proteins. Don't have to know for the test, but just kind of cool for the future. So this is an actual image of it. Again, a single cell, but you can see gaps between. or openings in, that is Endothelial cell membrane. There's your two basement membranes fused together And then there's your filtration slits between your pedestals of your podocytes. So things are filtered by size and charge, as I mentioned. So what things are filtered? Organic waste. organic good stuff. glucose amino acids. good stuff, electrolytes, really good stuff water And then hormones and drugs as well. things not filtered, red blood cells, white blood cells, platelets plasma proteins like albumin, really large proteins Fatty acids are not. They're a little bit too large. And then again, hormones and drugs, it depends on the type of hormone or drug. So that's scanning electron micrograph of a glomerulus. Does that get you excited? A little bit so this is the podocyte right there. There's its processes. a little filtration slits causes or forms. Not doing it for you. Look at this here. I mean, that is so cool. Anyways. So how do we get glomerular filtration to take place? Well. We have the Starling forces of the glomerulus. So, as we talked about before. with the Starling forces in the capillary, it's the same thing here. We are filtering. 180 liters a day of plasma. Just think about that. 180 liters a day. Your plasma is only three liters So we're doing like greater than 60 times of our entire plasma volume a day uh and you can say four to five times of your total body water male or female 35 to 42. So we have this glomerular filtration rate that we're going to be creating. The rate is what's the volume of blood we're moving through the glomerulus per unit time. So it's not a velocity, it's a rate. So it's the volume of blood per unit time In order for that to occur. We have to have some kind of pressure that is driving that. And so we have to calculate the glomerular filtration pressure we have this huge pressure that is favoring fluid to leave the glomerulus and go into Bowman space. And that should be… You tell me which one it is. E sub c, pi sub c, p sub i f Hi, Samaya. We'll just call them one, two, three, four. Which one is it? And people say one, the big fat green arrow. Some people say two. People say three. People say four. So we got one person that says one. Oh, what did you say? Four? A lot of people saying four and we got one person that said one. So it is one. So that's glomerular hydrostatic pressure, which is nothing more than what? Sounds fancy, but what is it? Glomerular hydrostatic. What is it? blood pressure, blood pressure in the glomerulus. So that's forcing fluid out. And then we got this small one there. What's the small one? One, two, three, or four. And one's gone. Two. So two would be two glomerular osmotic pressure. So is there a little bit of solutes in here that are drawing fluid out? Well, really not a lot, but it's a potential force. And then we look at the forces that favor fluid to stay in. What's the huge one? To which number? It's four. capsular osmotic pressure because what's in the capsule that's causing fluid to want to stay in. Sorry, I take that back. What's in the glomerulus that's causing fluid to want to stay in? This big arrow right here. means fluid wants to stay in. There's a draw for fluid to stay in. What's in the glomerulus causing that? Yeah, solutes, what solutes? Yeah, albumin, right? And some electrolytes as well, but largely albumin. And then we got this one. If we're moving fluid out here, there's going to be a little backlog of fluid that tries to push back in. So that would be capsular hydrostatic pressure. So again, we take the forces that favor fluid to stay. and we subtract them from the forces that favor fluid to leave. And then what we end up with is a net filtration pressure, which is our glomerular filtration pressure. which is 15 millimeters of mercury. Now, as a result of that, we'll have a certain rate And we're not going to calculate that in this class, but there's a certain rate at which blood's going to move per unit time. Sorry, a certain volume of blood moving per unit time, which is rate. Okay, so this is hemodialysis. Essentially what it is is an artificial kidney. So if someone has some kind of kidney problems. Maybe they only have one kidney. And it's not enough to handle the filtration of their blood. And what they can do is periodically go into a clinic And what we do is we take some blood out of their bloodstream And here it says artery typically it's a vein And what we do is we pump that blood into a dialysis bag. And this dialysis bag has this blue solution that has a certain concentration of solutes. We design it with a certain amount of solutes. We call it a dialysis solution. And the solutes are set up such that as this tubing that has your blood goes through that dialysis solution And really a dialysis solution just surrounds it. what happens is there's gradients set up so that the junk goes out. So you actually get rid of all the waste this stuff comes back, it's filtered, goes back to the venous side of your blood. Now, very often when people get dialysis, it's not an acute event. It's a chronic event where you're going in periodically to get this done. And again, largely the reason for this is you have some kind of kidney issue going on. So I've added these images and I'll make them available to you. So here's what they normally do for individuals that have to get chronic dialysis. they create something in their arm that is called a fistula. Anatomically speaking, a fistula is a connection between two bodily organs. So sometimes what happens with pregnancy is like the urinary system will have a a duct that connects it to the digestive system. In other words, women can end up with urine in their feces Because there's been a connection between their urinary tract In their digestive tract, their colon. So a fistula has formed. Here, we're creating a fistula. So what we're doing is we're actually taking an artery in your arm And we're stitching it into a vein. So we call these arterial venous fistulas. In other words, we're hooking the artery up to the vein. And what we're trying to do is we're trying to create high pressure in the vein. And we're trying to balloon that vein so also it's easier to access and poke. And when we balloon that vein, it gets strong and stuff like that. And now it's easily accessible. Also, you… create a little bit of high pressure in it. And by creating a little bit of a high pressure now, what you can do is draw blood out into the dialysis machine And then again, you can filter blood back in. So don't be alarmed if you see a patient someday that looks like that. So this is because of a fistula that was actually created by surgery underneath their skin of their forearm on the ventral surface of their arm. Sometimes… Because by the way, when you're trying to filter this blood with a pump. What happens is if people just have a vein that doesn't have high pressure in it. Let's say you don't have the fistula. the vein will just like suction close like a straw So we don't want that to happen. So we put some high pressure into it. That's the purpose of this. Sometimes people's vessels are very thin. And so what we'll have to do is put some tubing in here. So there might be some kind of prosthetic tubing in there instead of actual someone's of blood vessels. So GFR is the volume of blood filtered by the kidneys per minute. It's about 125 mLs per minute. which is 180 liters per day. Think about that. 180 liters Dave filter through the kidneys. glomerular filtrate reabsorbed is about 178. So that means there's about two liters a day. And you know that is our urinary output. So if we look at these images here. Substance A is a A good example of substance A would be inulin. Inulin is completely filtered. So when it gets into the glomerulus, 100% of it is filtered. And therefore, inulin is a good measure of your GFR. So we do something that's called inulin clearance. That is something you will be doing in your next level physiology class that you'll be freaking out about. People will want you to calculate inulin clearance. So we're not going to do it in here, but just know for here, and that'll be helpful for when you get to that next level. that it is an estimate of gfr And by the way, GFR is kind of like ejection fraction for the kidney. GFR is like how good your kidney function is so a good GFR, you know, normal GFR obviously is really important. Low Gfr is serious and indicative of kidney damage. Urea is a substance that is partially filtered and partially reabsorbed. And so you can see that Sorry, it's completely filtered. but partially reabsorbed. So you can see that not all of it makes it into the urine. There is some that is reabsorbed into the blood. Now, that sounds kind of counterintuitive, right? Because you would think that we would want to get rid of all the urea. basically a waste product to the body. But the reason we do this is for something called a urea trap. we want to trap urea not in our blood, but in the interstitial fluid of the kidney. So when I said that the medullary tissue of the kidney is concentrated with salt, it's not just salt, it's also urea. So urea and salt make that concentration gradient in the medullary tissue of the kidney. When we look at glucose, this is something that is filtered and completely reabsorbed. So unlike urea, where it's completely filtered But 50% of it's reabsorbed. For glucose, it's completely filtered, but all of it's reabsorbed. And where is all that reabsorption occurring? in the nephron. We're at. Are we going to wait to the DCT? Are we going to wait to the collecting duct? Where do we do it BCT right away. All that glucose is reabsorbed at the PCT. So much so people that all of that glucose that's in your blood, all of it was filtered into your kidneys. How much ends up in your urine? zip all of its reabsorbed right back into your bloodstream. Lastly, don't worry about this one. This is… periminohypuric acid. So it's an estimation of renal plasma flow and that is like way beyond the scope of the class. Don't worry about that. Okay, probably the coolest thing about the kidney is auto regulation. And it has to do with the purpose of the afferent efferent arterioles. So take a look at this here. This is renal arterial pressure. So this is the blood pressure in the kidney is basically what that is. Now, we all know it's going to fluctuate between these two, right? Between 80 and 120 because that systole and diastole. Now, if you look at that, as our blood pressure fluctuates between 80 and 120, Look at our glomerular filtration rate. It's constant. look at our renal blood flow, it's constant. And so renal blood flow is great, but I'm more interested in GFR. What's the rate at which we're filtering solute into Bowman space and therefore pushing it through the nephron as well. Take a look at this. What if your blood pressure increases to 160? GFR, constant. What if it goes to 180? GFR, constant. 125 mLs per minute. So what that means is that even if your blood pressure, even if you're hypertensive. and your blood pressure increases systole to 180 millimeters of mercury you'll still have a constant GFR of 125. And the reason why that's extraordinarily important is if you're filtering at too high of a rate. then there's not enough time to reabsorb stuff and things like that. So you had a bunch of waste that are still in your blood and you're dumping a lot of good stuff in the urine. So it's really bad to have a GFR that's too high. Which is not really that common. Which is much worse is to have a GFR that is too low. But that usually is an indication that there's a problem with the kidneys. So no matter all the way from 80 to 180, we have constant glomerular filtration no matter what the blood pressure is. The question is why? Let me just draw this really quick. here's the glomerulus. This is afferent arterial. This is efferent arterial. And look what happens. As blood pressure increases And really, I shouldn't be drawing that line up down here. As renal blood pressure increases. look what happens to your afferent arterial resistance. increases. Now, if the afferent arterial resistance increases, what does that mean? Is it vasodilating or vasoconstricting? The afferent arterial resistance is increasing. Is it vasodilating or vasoconstricting? Yeah, it's vasoconstricting. And so what that means is this. You got, let's say, 180 millimeters of mercury of pressure that is now pushing at a high rate blood this way. So how do you reduce that so that you can keep GFR constant? So what you do is you vasoconstrict the afferent arteriole. And now the pressure is still going to be high over here But on the downstream by the glomerulus. it's going to drop. And we can also play around with the efferent arterial. You can see that. efferent arterial resistance drops a little bit. We can also vasodilate this. So we vasodilate, vasoconstrict, afferent, efferent arterioles to regulate GFR to keep it constant. So here's how that looks. we have a high blood pressure that causes a high GFR. So look what we do. we constrict the afferent arterial that drops. the pressure here. in the glomerulus and the glomerular capillary and drops GFR. What if blood pressure is too low and GFR is too low? We vasodilate the afferent arteriole. that increases the pressure here. and increases GFR as a result of that. So that's the purpose of having a capillary network that's sandwiched by two arterioles. Not an arterial coming in and a venule coming out sandwiched by two resistance vessels is to maintain a constant gfr with not only changes in blood pressure, but also changes in renal blood flow as well. Okay, let's look at the PCT in more detail than the loop of Henley in more detail, then DCT in more detail, and the collecting duct in more detail. So here's the proximal convoluted tubule. And check this image out here. This is a simple squamous cell of the parietal lining of Bowman's capsule. And which one of these is podocytes? I don't know, but probably most of these are podocyte nuclei. That's actually red blood cells, red blood cells. There's Bowman space. That's the glomerulus. And check this out. In this image, we got lucky. we actually we don't have the vascular pull. Look, we have the urinary pole. part of the image. We actually see Bowman's capsule opening up into PCT. How do you know it's PCT? Wispy. Those little wispy microvilli. Okay, so there's proximal convoluted tubule for you there in purple. we take a slice out of it we look at it Please note our orientation. This is the apical surface of the cell. This is the basal. So that's the lumen. So the lumen's in yellow here Look out on the apical surface of the cell We have secondary active transporters, sodium glucose transporters, sodium amino acid transporters. We do secondary active transport to reabsorb all that stuff we didn't want to lose. So glucose and other organic solutes, that's how they get back into peritubular capillaries that are right here. secondary active transport. Now you can also see the bicarbonate buffer systems running here, so we can play around with pH as well. So what are we reabsorbing the PCT? Check this out, like 60 to 70% of water we lost with filtration Look, in order to filter those wastes in those unfortunately good stuff as well. We needed a vector. So we lost a lot of water. We don't wait to reabsorb most of it, 60 to 70%, we reabsorb right at PCT. 100% of glucose amino acids and vitamins are reabsorbed. 90% of bicarb is reabsorbed. 50% of urea. Again, we're leaving about 50% behind. for that medullary solute. And we can secrete some ammonium ions, proton, again, regulating pH. So just some terminology for you down there that I've explained before what reabsorption is. the movement of solutes from the lumen of the nephron to the kidney interstitial fluid. And ultimately, peritubular fluid will enter the peritubular capillary. Now, I'm sure you've heard that caffeine causes diuresis. In other words, make sure you urinate a lot. Well, so does theophylline, which is in tea. So caffeine and theophylline at the level of the PCT They cause diuresis by inhibiting sodium and water reabsorption. So by inhibiting sodium reabsorption, then sodium is going to continue past the PCT. And as it continues past, water will follow it. And so when water follows it, then we have this osmotic diuresis that's going on. Now, what's really cool is that there's a new drug on the market right now. It's called empagliflozin. Tempogliflozin or Jardian. So many people have heard of that on TV? So this new drug is really cool. It's an SGLT2 inhibitor. Now, the SGLT1s are in our small intestine. That's what we use to reabsorb Or let me take that back. That's what you use to absorb glucose in the small intestine. What do we use to reabsorb glucose in the PCT of the kidney We use SGLT2s. So what we do here is we use a drug that inhibits them for diabetes, type 2. Why? someone explained to us why this would be helpful for a type 2 diabetic. inhibiting their SGLT2s. Well, with diabetes, you have a poor regulation of blood glucose, right? So, and normally what happens is you have these episodes of hyperglycemia where your blood sugar is too high. So why don't we inhibit the SGLT so you can't reabsorb glucose? So where does it end up? So if we're blocking the reabsorption of glucose at the PCT with Jardians, where does the glucose end up? I'll give you a hint. Starts with a T. And don't help. Toilet. So it ends up in the toilet and that's good, right? Because it's not in your bloodstream So this is really good to help regulate people's blood sugar with type 2 diabetes. Now, what could be the downside of it? What do you got to be careful of? Say that. Potentially, hypoglycemia. What else? So when that glucose is cruising through the nephron on its way to the toilet, what is it dragging with it? water so you can become dehydrated, right? So you could have a diuresis that's going on. So here's the loop of henley. Actually, you can see that in a longitudinal view, which is kind of cool. That's Lupa penley right here. Right there as well. Really nice one with just two epithelial cells. So filtrate flows down the descending limb and up the ascending limb. That's why we call it countercurrent. And again, the descending limbs permeable to water but impermeable to solute. The ascending limb is permeable to solute but impermeable to water. Now, we've reabsorbed 60 to 70% of water at the PCT. And look what we have reabsorbed here in the descending limb, another 20. So like 80, maybe 90% maybe 85% of water has been reabsorbed By the time you get right to where that arrow is. And you might say, well, that's Jesus, most of water. There's not much less to reabsorb. Well, if you do 180 liters by the 15% left. It's still 27 liters of water that you still have to reabsorb. And so that will happen throughout the rest of the nephron. And obviously not all of it will be reabsorbed. We have to have some. or a vector to remove the waste from the body with urination. Okay, so here's the thick ascending limb where the big deal is. And again, all these people are getting it wrong, calling these pumps because there's the protein right there. The protein is called an NKCC2 So that stands for sodium potassium two chloride Simporter. Sodium, potassium, two chloride symporter. That's really cool, right? It's a simple order. It's four things in one direction, four ions in one direction. And what's driving it is sodium. So the sodium is driving the potassium to go and the chloride to go because on the basal side of the cell. sodium potassium pumps. So that you have the gradient to draw this stuff in. Now, what happens is you got the potassium here and you got the chloride here. But the sodium potassium pump moves potassium back that way So you end up with sodium chloride here. and of assault. But what's also going to be there from a different mechanism is urea because of the urea trap. Now, let me tell you something cool about this. How many people have heard of diuretics? People have heard of LASIK? So Lasix is like one of the most common ones. And so here it is. And the chemical name is furosemide. So what does it do? It blocks NKCC2s. to think about what would happen if you block an NKCC2. So if you block this. then you can't. reabsorbs salt here. That's blocked. So if you can't reabsorb salt here, that means what you're doing is normally the kidney looks like this with a lot of solute in the interstitium. Now it looks like this. So now what happens if you want to reabsorb water So remember, we're reabsorbing water at the PCT, we're reabsorbing water at the descending limb of the honey. What happens to that? It's impaired, right? The gradient's way down. So your ability to reabsorb water is impaired. So the water stays in the tube and ends up where? in the toilet. So what happens as a result of that? So your blood volume drops, right? And then what happens as a result of that? Your blood pressure drops. That's why furosemide people is a drug for hypertension. So it's a way of dropping blood pressure by way of dropping blood volume. You inhibit NKCCTs. We call these loop diuretics because they work on the loop of Henle. Now, the problem with this diuretic is that it's also going to cause potassium to be excreted in your urine. And some people are really sensitive to that. Let me say that your sodium potassium levels are all exquisitely regulated by your kidney. So if you ever get a metabolic profile from your doctor, look at your sodium levels, your chloride levels, your potassium levels. They're in a very, very, very tight range. And every time you go to the doctor, they're going to be right in that tight range. So the kidney is amazing at keeping them at really strict levels. And the reason for that is if potassium gets too high or too low and add that with sodium as well, but potassium in particular. then cells start freaking out. Their membranes become irritable. They start spontaneously depolarizing. And all of a sudden you got all kinds of arrhythmias going on. So it's really serious. So potassium levels are too high, too low, people have arrhythmias, they could have sudden cardiac arrest, all kinds of crazy stuff can go on. So some people are actually more sensitive to that than others. So we have to give them diuretics that don't also cause that. We call them potassium sparing potassium. diuretics. We'll get to that in a second. So this is the kidney current multiplier. Someone in a next level class is going to make you learn all about this and freak you out about it. And it's really a simple process. They're going to probably make you do math and all that stuff. But really, I think none of that is important in understanding the fundamental process of this. So this is the loop of Henle. And you got 300 milliosmolar of solute coming in. Big whip. I'm not going to ask you to remember that number. But look what happens. We reabsorb water here Because we have a gradient there. And why do we have the gradient here? Thanks to who? thick ascending limb and NKCC2s, right? Write that down. Thank you. And now the solute concentration gets really high, big whip. On the ascending limb, we were impermeable to water, but what we do is we move salt Sorry. We moved SALTA by the NKCC2, right? And we're moving it everywhere. So now we're concentrating the medullary tissue with solute. So that's the NKCC2 action right there. And now we're back to about the same dilution. Big deal. The point, though, is that loop of henley has allowed us to create a medullary concentration And the reason why the juxtamedullary nephron loop of Henle is as long as the medulla is because we want that gradient to run the length of the medulla. Now, let me say something here. We have to feed the nephron with blood, right? We have to keep the nephron alive, but we also need peritubular capillaries. Imagine that the peritubular capillary just did this. Imagine that the blood vessel came in and then just kept cruising. what would happen is all that solute would jump into your blood So first it would go to the interstitial space But then it would jump into our bloodstream. And then that blood vessel would cruise off to wherever and it would take all the salt with it. So as the blood vessel is coming down, there's more solute in the interstitial space than the blood vessel. All the solute goes in the blood vessel and the blood vessel takes off. So here's the reason why we have a vasorecta. So instead of the blood vessel being straight, we make it do a hairpin turn just like the loop of Henley. So indeed, as the blood vessel comes down, the descending limb of vasorecta Indeed, we pick up salt. we take all that salt out of the medullary tissue Well, look what we do on the ascending limb. we dump it right back out. So we still nourish the kidney. And we maintain that concentration gradient as well. And there's no washout of the solute in the medullary tissue. If it wasn't a hairpin turn like that, we would just wash the solute out. So that's what maintains the gradient there. Does that make sense? So again, people are going to want you to calculate numbers because it's called the kidney countercurrent multiplication system. I think that's important. I think what's important is just to understand that it's responsible Look, this is responsible for creating the gradient This is responsible for maintaining The gradient. So distal convoluted tubule. This is DCT, DCT, nice and smooth. Cells? No. wispiness. That's a huge proximal convoluted tubule right there. Another one there. Look at this guy right here is smiling at you. Couple eyes, a little nose there. has a little capillary right there. a couple little capillaries down there. And look, you can see the connective tissue there. That's collagen. And just to remind you, no images on the exam. I know I'm excited about it, but not on the exam. All right, so here's distal convoluted tubule. What's shown over here is entire distal convoluted tubule. And what's shown over here is just like the last portion of it before the collecting duct. Now let's talk some more about diuretics. Well, actually, before that, what does the distal convoluted tubule reabsorb? some sodium if you have aldosterone. Because aldosterone stimulates what? upregulation of? An increased activity of That aquaporins, good guess. Sodium potassium pumps. Sodium potassium pumps. Look at this. Someone mentioned earlier, which I believe it was that individual right there. that you've got a regulation of calcium homeostasis by PTH and calcitriol. here at the DCT. And then we can play around with proton and bicarb. Again, we can play around proton and bicarb by secreting it. And then drugs and toxins. Again, DCT is often thought as like a backup till filtration for whatever you want to get rid of that you didn't during filtration. We have drugs that are called thiazides that are also diuretics. How many people have a family member that says, hey, I take this along with my water pill? Yeah, so what they mean by that is this. thiazides. So the water pill is typically a thiazide. Maybe you'll hear about it as like a hydrochlorothiazide. So someone will be taking a beta blocker with a thiazide. Pretty common. Usually combination therapy is required to properly treat hypertension. So what do these thiazides do? So the thiazides inhibit sodium chloride supporters. Again, we're in the apical border. This is a sodium chloride symporter that would bring sodium into the cell But we're blocking that. Now, why is that important? Well, if we block that, then sodium is not going to go here And then sodium is not going to go here. And so the solute concentration of our blood is down. And moreover If the sodium is not going that way, it's building up here. that's the lumen of the tubule. So that means sodium is going to cruise along your tubule now into your collecting duct. What's it dragging with it? water by really we can say osmotic diuresis we call it natural recess because it's sodium that's dragging the water. Now, think about this. If you block this and sodium builds up here. That means that sodium is going to keep cruising along the distal convoluted tubule. So now you've blocked it. sodium is high in here now. But that means sodium's high in here now as well. So when it gets to the later portion. sodium comes in. drives the sodium potassium pump now you're losing potassium. So in other words. By blocking the sodium chloride supporters here, you're increasing what we call the sodium load in your nephron in the tubule. And by increasing that load, that's great. Water is going to follow it. But when that high load gets to later portions of the distal convoluted tubule. that sodium will come back in through these channels drive the sodium potassium pump and now you're going to lose potassium as well. So again, thiazides people are sensitive to because they get potassium loss. So how do we deal with this? Well, again, we give what we call potassium sparing diuretics. And again, for those individuals that are really sensitive to those changes. By the way, make no mistake about it, if a physician is giving someone thiazides, they're checking their blood for their potassium level. No questions asked. So we got a couple ones. One is called spironolactone and the other one is called amiluride. Look what spironolactone does. It antagonizes aldosterone. Now, I just said aldosterone upregulates and increases the activity of sodium potassium pumps. But we're antagonizing that. So if we antagonize that and sodium potassium pumps are not working as much Well, then you're not moving that potassium there. So that's good. And then there's another one called a milluride that just blocks these. That's called an epithelial sodium channel, an ENAC. If you block that, you just directly affect sodium. We don't affect potassium at all, just sodium. And by the way, this is just the aldosterone sensitive portion of the DCT. After this, you go into collecting duct. So very common, a potassium sparing anti Sorry, potassium sparing diuretics. Again, all drugs used for hypertension. Now, let me say that there's other reasons that people take diuretics So you could have other reasons where you have like some fluid volume building up in your body and you're trying to get water out of your body. Like heart failure, things like that. But generally speaking for hypertension. So collecting duct. Yeah, big deal. It's probably collecting duck. It's been too long, not sure. That is, that's really nice collecting duck. I'm going to tell you why. And someday maybe you'll thank me. Cuboidal cells the nucleus is right in the center. Because the cell is pretty much as tall as it is wide. columnar cells, their nucleus looks like this. It's towards the basal side of the cell. We say it's basally shifted. So look at these nuclei. They're close to the basal side. There's a lot of apical cytoplasm there. And when you know it's columnar, you know it's collecting up. Just in case. you want to know. So what's going on in the collecting duct? We got some reabsorption secretion of Proton bicarb to regulate pH. So now you've learned that every portion of the kidney can do this. help regulate our pH. Sodium chloride is being reabsorbed. water is being reabsorbed by the influence of ADH, antidiuretic hormone. And then urea because of the urea trap. So this is the normal situation right here with no ADH. Here we are using the NKCC2s to create a solute gradient. And that solute gradient is causing water to be reabsorbed largely at the descending limb of loop of Henle. Now, if for some reason our blood volume is down. And we need to get our blood volume up. Maybe our blood pressure is too low. We need to get our blood volume up for that reason as well. What we can do is we can secrete ADH. and ADH can bind to our collecting duct cells And when it binds to them, it puts aquaporins in their membranes. And when you put aquaporin in the membranes of these cells, these collecting duct cells. Now water can move. But here's the hitch. Remember from the beginning of the semester. In order for something to move across a cell, you need two things. You need a pathway and you need an energy source. ADH just created the pathway. It put aquaporins in the membrane. Well, what's the energy source? Well, it's an osmotic gradient. Well, who created that? this. So here's the deal. If you block NKCC2s. with furosemide, then this ain't going to do anything. ADH ain't going to do anything because you got the pathway, but you don't have a gradient for the water to move. So in a normal circumstance, our volume of our urine will be relatively high and it'll be dilute. But if we need to increase our blood volume for whatever reason. then the water output will be lower So our urine output will be lower, but it'll be very concentrated. Okay, so I think we've talked about this before. We got blood volume, blood pressure regulation at the level of the kidney. So we have an increase in plasma osmolarity, increases interstitial fluid osmolarity. And that stimulates superoptic neurons. So we actually believe that these super optic neurons are baroreceptors in and of themselves. So I think this slide, we looked at it before, but I think it should make much more sense now. So if for whatever reason your extracellular fluid osmolarity is high. I mean, there's a lot of solute floating around the superoptic neuron. then it'll stimulate this neuron to fire action potentials. It'll release ADH. herring bodies. ADH will go to your blood vessels, but also it'll go here to the V1, sorry, V2 receptors here and put aquaporins in the membrane of the collecting duct we reabsorb water and that dilutes out that extracellular fluid osmolarity. So good negative feedback. Meanwhile, the volume output of our urine is going to be low. But the solute concentration will be high. So that just means osmolarity of urine. Now, alcohol inhibits superoptic neurons, and that should explain to you diuresis with alcohol consumption. So people are known to urinate a lot when they drink alcohol. It's because super optic neurons are not firing like they should. When someone drinks alcohol. diabetes insipidus we talked about. We said it has nothing to do with diabetes, mellitus, and blood sugar. There's two forms, the central form, we're not secreting ADH properly. So clearly that's a problem with keeping blood volume up so we're losing volume in our urine And then there's nephrogenic form where our V2 receptors are jacked up. And the V2 receptors is where ABP binds to and causes aquaporins to be put in the membrane. So there's no upregulation of aquaporins, so there's excessive loss of water in the urine. So diabetes insipidus means basically to pass through tasteless. So something's passing through the body that has no taste to it, i.e. water. Okay, so the last thing is the most important thing. The renin-angiotensin-aldosterone system, which is called RAS. You're going to see this a million more times. So check this out. I said JG cells are chemoreceptive. But they're also baroreceptive. This is the baroreceptive thing. So if the blood flow that is coming into the kidney through the afferent arteriole is under too low of pressure. those GAG cells can sense that. So if your blood pressure is too low, your kidney is sensing that. Specifically, GAG cells. And what do they do in response? They spit out renin. And what does renan do when it's in your blood? they can convert this circulating zymogen called angiotensinogen to angiotensin 1. That's what renin does. Who do you think makes angiotensinogen? who's the altruistic organ of the body? Liver made sense. It's always circulating around. So look, blood pressure is too low in the kidney. JG cells sense that because the afferent arteriole is not stretched enough. Spits out renin. Renin converts angiotensinogen to angiotensin I. Great. Angiotensin 1 itself does nothing. But in your lungs, there is an enzyme I think I have it on the slide. In your lung, there is an enzyme called It's expressed on your endothelial cells in your lungs. What does it do? It converts angiotensin 1 to angiotensin 2. That is a big deal. Angiotensin II is a vasoconstrictor. It does all kinds of things. So let's look at the things it does. stimulates your zonal glomerulosis cells to produce aldosterone. Increased blood volume, increased blood pressure. basal constricts your vasculature, increased blood volume, increased blood pressure. stimulates the thirst centers in your brain. In other words, makes you go drink water to increase blood volume, increase blood pressure. stimulates the release of ADH. to increase blood volume, increase blood pressure. And probably the most important thing is this. It's a major vasoconstrictor or V1 receptors. Now, why is this all important? go to a pharmacy next time you pick up medication that you have. And just ask them, what's the number one blood pressure medication pumped out this window? And they'll tell you one of these two. So one is lisinopril and one is losartan. So lisinopril is an ACE inhibitor. If you block that, you can't convert ace one to ace two. So now you're reducing this vasoconstriction in your body and this reabsorption of water. You're decreasing blood volume and blood pressure. Another one is called losartan. And for Losartan, we don't care if angiotensin 2 is made. What we do is we block its receptor. So an ARB is an angiotensin receptor blocker. These are the like most two common drugs other than metoprolol pumped out the window. Now, last thing that's kind of cool, just a personal edification If you look at an endothelial cell in your lungs. it has ace has ace One, an ACE1 looks like this. It's an enzyme expressed on your endothelial cells. And it's got ACE2. Check this out. For some weird reason that nobody knows SARS-CoV-2. its spike proteins bind to ACE2 And this does receptor mediated endocytosis. That's how the virus gets into our body. So it binds to ACE2. By the way, ACE2 degrades angiotensin 2 and angiotensin 1

The kidneys are retroperitoneal organs located behind the peritoneal membranes, with the right kidney positioned slightly lower than the left due to the liver above it. Each kidney has a hilum where the renal artery and renal vein are located, as well as ureters that transport urine to the bladder. The kidney's anatomy consists of an outer cortex and inner medulla, containing renal pyramids. Nephrons, the functional units, filter blood and produce urine through processes in distinct segments: Bowman's capsule, proximal convoluted tubule (PCT), loop of Henle, distal convoluted tubule (DCT), and collecting duct. Filtration occurs at the glomerulus, where both waste and useful substances (like glucose) enter Bowman's capsule. The PCT mainly reabsorbs water and nutrients, while the loop of Henle creates a concentration gradient for water reabsorption. The DCT further regulates ion levels and contributes to blood pressure control. The collecting duct, under the influence of ADH, can adjust water reabsorption based on the body's needs. The renin-angiotensin-aldosterone system is critical for regulating blood pressure and fluid balance, responding to low blood pressure by triggering hormone pathways that increase blood volume and pressure.