Urinary Physiology - Module 10 - PDF

Record. All right. Awesome. So module ten is urinary physiology. Now, when I first took physiology, I thought that learning about the kidneys was going to be super boring. But it's actually one of the most complex and intricate systems that we're going to learn. And it's very intuitive and it follow...

Record. All right. Awesome. So module ten is urinary physiology. Now, when I first took physiology, I thought that learning about the kidneys was going to be super boring. But it's actually one of the most complex and intricate systems that we're going to learn. And it's very intuitive and it follows a lot of patterns. So I think you're going to find this unit, um, quite satisfying. And we're going to start off with some anatomy review. Just so we're all on the same page. So the urinary system consists of a few key structures. This picture might look familiar from an anatomy lecture. So let's review those key structures in the urinary system. First really the stars of the show. We have two kidneys in the lower abdominal region of the body. So they are shaped like little kidney beans. Or I think the bean was named after the organ. But anyway, here we have our two kidneys, one on the right, one on the left, extending out of the kidney. Let's do green. We see this long tube coming out of both kidneys. We call that the ureter. So the ureter is what brings the urine that was formed by the kidney out of the kidney and directly into this collapsible muscular sac down here, which is the urinary bladder. So the bladder is made out of smooth muscle that can distend. It can stretch as the bladder fills with incoming urine. And then coming out of the bladder, we have the urethra. Now the urethra is going to transport all of that urine out of the body through the external urethral orifice. And so the kidneys are pretty cool because they are responsible for removing waste from the body. Now, there's a few other systems that participate in this. So the removal of waste products is accomplished by our respiratory system. Right. Breathing out carbon dioxide. That's what we talked about last week. Our digestive system gets rid of waste products right as fecal matter. Our sweat glands get rid of waste products in our sweat. And then of course, the urinary system gets rid of metabolic wastes through urine. Now, out of all of these systems combined, if we want to think about the one that is like the primary way of getting rid of waste in your body, that's the urinary system, which may be you might not think you might be inclined to say respiratory or digestive, but it's the renal system. Okay, so like I said, the kidneys then are the major organ of the system. They are the organ that's actually responsible for forming urine. Now think back to that lecture that I gave on blood. I told you, there's so many different things found in our blood. We have water. We have red blood cells. We have hormones, waste products, ions. So there's really so much in our blood at any given moment. And so the role of the kidney then is to go through our entire blood supply, all five liters of it and pick out the waste and then return the stuff that we want to keep back to our general circulation. Okay. So all of the blood in our bodies is going to pass through the kidneys at some point in time. Multiple times every single day. So how do we welcome in blood initially into the kidney. That's going to be through the renal artery. So the renal artery is hidden here. It's this red vessel in the back. So the renal artery is bringing blood that has not yet been filtered or sorted through by the kidney. And then you'll notice that the renal artery is going to split and branch into smaller and smaller blood vessels or arterials we call them. And the purpose of that is inside of the kidney. We have individual cells or functional units that are going to go through your blood. They're going to sift through it, pick out the waste products, make sure that those get removed, and then help you keep the stuff that you need to keep. And so that functional unit of the kidney, the cells that actually accomplish this, we call those nephrons. And so the nephrons there's at least a million of them in each kidney. And so we could just picture microscopically that deep in the kidney we have a lot of these nephrons that are sorting through your blood. And in fact we're going to talk about how the nephron is mostly contained in this outer region of your kidney, which is called the renal cortex. Part of the nephron is going to dip down into this middle portion, which we called the medulla. Right. Medulla means middle. So this right here is the renal medulla that will contain part of that nephron. And so the goal what's happening out here in the kidney millions of times is we are sorting through your blood. Now, once you've sorted through your blood, there are, you know, the majority of what we sort through, we want to keep. Right. Because think about how many times you urinate a day right there. You know, it's a decent amount, but you're not urinating every five minutes, right? So all of the blood that we've filtered through, we've decided what we want to keep. That's going to go back to our general circulation rate to the rest of the body. And so that blood that we've decided to keep is then going to pile or be compiled into veins. And so all of these blue vessels are carrying that's now filtered blood out of the kidney. We want to leave. And that newly filtered blood is going to leave the kidney through the renal vein. The renal vein then goes back to your heart and then circulates that blood all over again to the rest of your body. So that's blood. What do we do with the urine that we formed that has all the waste that we want to get rid of? So, like I said, the nephrons are going to be mostly localized to the outer cortex and a little bit of that renal medulla. And so the urine that we do form, it's going to then be emptied into this opening in the kidney called the minor calyx. And then eventually it's going to open up into this renal pelvis. All of the urine is going to collect and kind of congregate here in the renal pelvis. And then we want to get rid of that urine so that urine will be excreted out of the body. Well I should say it will be taken out of the kidney first through this ureter which we saw in the previous slide. Now the ureter is going to carry that urine to the urinary bladder, where it will be stored until you're ready to urinate. So that's just the general idea. We are doing two things in the kidney. We're filtering through all of the blood in our bodies. Getting rid of the waste and then excreting that waste as urine. But the kidneys do so much more than just generate urine. Their actions are going to have major consequences on our cardiovascular system, um, as well as our blood. So functions of the kidney. The first is that it's going to filter blood plasma. Okay, so plasma is the watery part of your blood. The part that has water, ions, hormones, nutrients and waste. So what your kidney is doing is it's looking through that plasma. Well, it's looking at all of your blood. But what it's really going to filter out are things that are small, like things that are in your plasma. So the kidneys are separating waste from anything that's useful in the blood plasma. And we're going to return the useful substances back to our blood supply, back to our bloodstream, and then get rid of what we don't need. Get rid of the waste. That first function is probably the most intuitive. You're like, yeah, that makes total sense. The second one, though, might be pretty shocking. So the second function is that the kidneys are going to regulate your blood volume and your blood pressure. How does that work? Well, we know that plasma has water in it, right? Blood contains water. What the kidneys are doing is they are going to regulate how much water we retain, how much water we end up holding on to versus how much water is in our urine. So the more water that's in our blood plasma. If the kidney is allowing us to retain a lot of water. We have more water in the blood. So that means that blood will have a higher volume. There will be more of your blood. So the higher the blood volume is, the more blood you have, the higher your blood pressure is going to be. Why is that Will? Because if you have more blood, your heart is going to need to generate more force to push that blood throughout your body. So I know we talked about pressure and volume last week, but that was relating to gases. Now we're talking about a liquid. So here for this lecture. The higher your blood volume is, the more water there is in your blood, the higher your blood pressure will be. Your heart has to work harder to send that blood out to other places in your body, because you have more blood to send. All right. And so this third function is very closely related to water retention. So the kidneys are going to regulate the osmolarity of our body fluids by controlling how much water and solutes. So think ions are excreted out in your urine. So I'm going to show you in a later slide just how the contents of your blood, how much water is in it, how much salt is in it, is going to impact the extracellular fluid that surrounds your cells. Um, so the amount of salt in water we retain in our blood will impact that extracellular fluid. And I'll show you this in a later slide. Right. Because osmolarity is asking how concentrated is this solution. If we're looking at the big picture with how much water is in it, how much salt is in that solution. So we're going to play around with that. The kidneys also secrete an enzyme called renin, which we will talk about today. And renin is going to activate this whole system that helps you maintain your blood pressure and to increase your blood pressure, your blood volume. And it's going to help you retain salt. And then the kidneys also secrete the hormone erythropoietin, which we talked about when we talked about blood. And erythropoietin stimulates the production of new red blood cells every single day. So the kidneys do so much more than just make urine. All right. So what we're going to do first is we are going to zoom into this picture and we're going to review one more time what's going on in the kidney here. So like I mentioned the kidneys are sorting through all of your blood that is in your body, all five liters or 4 to 5l depending on how tall you are. So the unfiltered blood enters the kidney through the renal artery. The renal artery is going to split and branch into smaller and smaller blood vessels. And it's the smaller blood vessels that are going to feed into the functional unit of the kidney, which is called the nephron. Once the nephron has done its job and it's filtered through blood, the filtered, now filtered blood is then going to enter these blue vessels. The blue vessels come together and then eventually leave the kidney through the renal vein. And the renal vein goes back to the heart to circulate that blood all throughout your body. The job of the nephron is to eliminate waste from your blood. So the waste products are then going to leave the kidney as urine through the ureter. It's going to go to the bladder. So if we were to take a cross section here. Through this portion of the kidney. This tiny little sliver. We can observe what's happening on a smaller scale. So this right here on the right this is our nephron. Now the nephron gets a little crazy because there's two components to it right. Because let's think big picture. What is the kidney doing. Filtering through our blood and generating urine. So there's going to be two components to it. There's going to be the blood component where all of our blood vessels are. And then there's going to be a series of tubes that I usually put in a tan or gold color that contains urine. Right. Because there's two things going on here. So this nephron is this entire thing. It's the functional unit of the kidney because it's the smallest component that can actually make urine. And so each nephron has a vascular component and a tubular component. All nephrons. If we zoom back in. All nephrons start in the outer cortex of the kidney, which we call the renal cortex. And then part of their structure will dip into this middle area, which we call the renal medulla. All right. So what do I mean by vascular component to the nephron. The vascular component is basically anything that's a blood vessel. So it's either going to be red or blue or like a mix of the two. So the vascular component that's the part of the nephron that will be continuous with your blood supply. These are things that your body is going to keep. The tubular component are the gold or tan colored tubes that have a very like distinct shape. And so the tubular component is going to hold on to the fluid. That's eventually going to be urine. Okay, so the tubular component is continuous with what eventually becomes urine. Now we're going to talk a lot about fluid today. And I'm going to use these words kind of just like loosely. So I want to make sure that we're all on the same page here. So. The fluid that's in the vascular component of the nephron. That's your blood. Whole blood. So the part that has red blood cells, white blood cells and plasma. So the vascular component is continuous with your blood supply. It's eventually going to return back to your general circulation. Now as we go through this lecture, if at any point we're talking about, you know, the vascular component or if something is in the blood supply, anything that's in the vascular component, I want you to equate that with. That's the that's the thing that my body is keeping. Those are the weights or solids or whatever that I will hold on to after this whole process is said and done. These are things that are kept by the body. The tubular component, the structures that are gold or beige, that contains the stuff that you filtered out, that's your filtered blood plasma. Okay. Remember, plasma is the watery component of blood. It has a lot of waste products. So anything that's in the tubular component you've sorted through you want, you're most likely will want to get rid of it. And here's the thing. We call that fluid that's in the tubular component the filtered blood plasma. We call that filtrate. And I'm going to use that word a lot in this lecture. So the filtrate is what will eventually be excreted out of your body as urine. So if fluid is within the tubular component of the nephron. I want you to think, oh, that's what's going to be removed as urine. That stuff that my body is getting rid of. Okay. So now that we laid the groundwork. Now let's actually look at each component in more detail. So let's look at the vascular component of the nephron right. So that's basically all of the blood vessels that are part of this structure or functional unit. So first we'll start off with the renal artery. So like I said the renal artery is bringing in blood that has not yet been filtered by the kidney. And then the renal artery is going to split and branch into smaller vessels. And we'll zoom in for this so we can see. Now, the blood vessel that's actually bringing in unfiltered blood into the nephron is this little guy down here, which is not labeled. Shame on me. This blood vessel is called the afferent. Arterial. We know that arterials are smaller blood vessels and afferent means coming at. So this afferent arterial is going to bring blood into this little cluster here. And this cluster of capillaries in the nephron is called the glom malleolus. Okay. So the afferent arterial is the blood supply that's coming at the glomerulus, which is this tuft or a collection of blood vessels here. The glomerulus is one of the most important parts of this entire thing. So the glomerulus. Like I said, it's a tuft or collection. Of capillaries here. And it's the blood that's in the glomerulus that's being filtered. Okay. So the kidney is then going to filter through some of the blood in the glomerulus. And we begin the process of forming urine. Okay. Next, leaving the glam list. We have this tiny blood vessel back here. This is called the Efferent Arterial. Which is labeled as number four on the list, but I'll just write that out. E Ferencz. Arterial. So this is exiting the amaryllis. And then you'll notice that surrounding the rest of the nephron, we still have blood vessels. We have capillaries that are surrounding the entire thing. So all of these blood vessels here that are surrounding the rest of the nephron. They're red and purple and blue. Everything. Those are your Perry tubular capillaries. And so just to really drive home this point. All of the blood vessels that I'm highlighting in green. Those are all Perry tubular capillaries. So it surrounds the majority of the nephron. Like. 80% of it. Okay. So this is a blood supply that's going to surround the entire nephron. And these capillaries are important because it's going to be involved with some communication some some back and forth communication between the blood supply and what's going to be in the tubular component of the nephron. So the gold part, the gold tubes. So we're going to have some exchanges going on which we'll talk about. And then eventually the Perry tubular capillaries come together to form venules in the kidney. Uh, but the part that I care about is that all of those Perry tubular capillaries come together to form the renal vein, and then it's the renal vein that leaves the kidney entirely. So these Perry tubular capillaries are super important. Hey, they surround the entire nephron. Now what we're going to see is some nephrons have a really long loop of hennelly which we'll talk about. Um, so in certain nephrons there's going to be an additional blood vessel network called the vasa recta. But we're going to put a pin in this and we're going to come back to it. Right. Now let's look at that tubular component. So again anything that's in gold or yellow that's the tubular part. So the tubular component of the nephron, it's basically a hollow tube that's going to be filled with fluid. Now what fluid is inside of the tubular component? It's everything that was filtered from your blood. I'm going to tell you specifically what those things are in just a bit. So things were pushed out of your blood supply into this network. This tube network. And what's really cool about the tubular component is it's made out of a single layer of epithelial cells, which makes it ideal for diffusion. So the key here is like once something is in the tubular component, it's not a done deal. There is a potential for things to leave the tubular component to go back into the blood supply. How does it get back into the blood supply? Well, we saw here that there is a capillary network that surrounds the entire thing. So the kidneys are very flexible, right? It can decide what things it wants to hold on to or get rid of. So diffusion is going to happen a lot here. And so the tubular component is continuous, which means that one part seamlessly blends into the next. Um, it is divided into different segments, and each segment is going to be permeable to different things. Certain things are going to happen in some areas. So it is divided into different zones. And so let's look at those zones now. And for this we're going to zoom in. So like I said, the nephron originates in the cortex, in the outer cortex. So that's what this area up here is the cortex down here this represents the renal medulla which is that middle segment of the kidney. And so we start with the glomerulus. Right. The amaryllis was that tuft, that collection of capillaries. That is the start to the nephron. Our first component of the tubular component is this double World Cup that surrounds the glomerulus. And we call that double World Cup Bowman's capsule. So think of it as the cup that's catching all of the things that we're filtering out of the glomerulus and pushing into the tubular component. So Bowman's capsule is the cup that's catching all the remnants that we're filtering out. Okay. So it's going to collect fluid and waste products that were filtered out of the glomerulus. And then straight off of Bowman's capsule we have the proximal convoluted tubule also known as the p c t. The PCT is within the renal cortex. It's a pretty short area, and it's going to help us retain some salt and some water, which we'll see. And then the PCT is going to form a new segment. So the next segment. Is this U-shaped hairpin loop that dips far into that renal medulla. We call that loop the Loop of Henley. Okay. So the loop of Henley, which you can already tell has some differences in its structure. Right. So this descending part here that dips down into the medulla is thinner versus this part up here that's ascending back up to the cortex is thicker. And there's going to be different things going on in each region. So the loop of Henley goes down into the medulla. It goes right back up. It's going to go back up to the renal cortex. And then this outer portion here is called the distal convoluted tubule. Okay. The distal convoluted tubule is still within that renal cortex. And then the distal convoluted tubule is going to become the final zone of the tubular component, which is this entire duct here which is called the collecting duct. So the collecting duct is once again going to plunge into that renal medulla. And then be collecting ducts of multiple nephrons are going to come together and empty that urine that they formed into the renal pelvis, which I showed you. Earlier at the start. Okay. So the renal pelvis is going to collect that filtrate or that urine from multiple collecting ducts that belong to different nephrons. All right. Now this slide here, it gives an overview of the function of each region of the tubule. But we're going to go through everything in detail. So it's a bit redundant if I tell you this now. And we haven't even talked about it. So I'm going to skip this slide. And we're going to move on because we'll cover it in more detail. All right. So again filtrate is a big word I'm going to be using today. So filtrate. Is your filtered blood plasma. So this is these are the things that were filtered out of your blood stream and are hopefully going to be excreted out of your body as urine filtrate contains a lot of water. Salt, NaCl and waste products. So if you take in Advil or an aspirin new metabolize a certain medication, the waste products get removed. Waste products from metabolism, from muscle contractions, from building proteins all of that will get removed from your body. So how how does that filtrate flow throughout the kidney? Well, we saw that filtrate is initially formed in Bowman's capsule in that double walled hub. That's where things first started. From there it goes into the proximal convoluted tubule, which was that next region, then into the loop of Henley. People also call it the nephron loop means the same thing. You can use either term. Then from there it goes into that distal convoluted tubule and then the collecting duct. And then as I mentioned, the collecting ducts of multiple nephrons are going to carry that filtrate into the renal papilla first. Which is this initial segment here. Then it goes into the minor calyx, which then feeds into the major calyx here. Which then goes into the renal pelvis. From the renal pelvis. It's going to leave the kidney through the ureter. Then goes to the urinary bladder, which stores urine, and then the urinary bladder excretes that urine out of the body through the urethra. Okay. All right. Now there are different types of nephrons, and what distinguishes them really is how long the loop of hennelly is. There are some nephrons that have a really short list of hennelly. Some of them have a longer one, and that's going to play a role in water conservation. So we'll start here. So in both of these pictures, the area that's shaded in light pink, that's corresponding to the renal cortex the outer portion of the kidney. The darker color down here corresponds to the renal medulla, which is getting into the middle part. And let's take a look at this nephron here. And I'm going to zoom in. So this nephron is what we call a cortical nephron. It makes up about 80% 85% of all of the nephrons in your kidney. We call it cortical because they have a pretty short loop of hennelly that, you know, doesn't really dip too far down into the medulla. So the majority of the nephron is in the cortex. That's why it's called cortical. Now what's important to note is in these cortical nephrons they are smaller. They are shorter. The blood vessels that surround the rest of the nephron, or I should say the majority. We just call those hairy tubular capillaries. Okay. So the Perry tubular capillaries surround the PCT. The loop of hennelly the DCT. And then we have the other type of nephrons. Which are these ones? We call them just medullary nephrons. And what you'll notice right off the bat is that they have a long loop of hennelly that goes pretty far down into that renal medulla. These nephrons are pretty rare. They make up about 15% of the total nephron population in your kidney. And they have a long loop of Henley. Now, what we're going to discuss today is the loop of Henley. Helps us to concentrate. It's going to make sure that the urine that we do put out has to make sure that it doesn't have too much water or too much salt. Which we'll talk about. And so this long loop of Hanley is going to help us maintain a salty gradient in the medulla. So I'll just say this now the renal medulla is a very salty place. It gets saltier the further down you go. And we'll talk about this a bit more. And so these long loops of hennelly are going to make it so that we retain, that we hold on to as much water and as much salt as possible. Now remember I said those Perry tubular capillaries? In these jokester medullary nephrons. When they surround that long loop of Henley. We call that blood vessel network. The vasa recta. And this is also on the next slide. So the key to know in these jokes DiMaggio Larry Nephrons with the long loop of Henley, the capillaries that surround that long loop of Henley has a special name, because there's a special process that's going to be going on here. You call that the Vasa rectum? Whereas in the cortical nephrons, the blood vessels that surrounded everything, was just the Perry tubular capillaries. Now there are some animals that live in places that don't have a lot of water, right? Like the desert rat. It's a cute little animal of the desert rat would have a high proportion of these just imaginary nephrons because they live in the desert. They don't have access to water as readily. So, you know, based on evolution and how they've evolved, um, they're able to retain as much water as possible, as much salt. So there are some animals that have a significantly higher proportion of these jugs to medullary nephrons, if based on their environment, which I think is pretty cool. All right, here we go. So like I said in these jokes, the medullary nephrons, you can see just how far down into the renal medulla that loop of hennelly gets. Perry. Tubular capillaries surround the proximal convoluted tubule in these nephrons, um, as well as the distal convoluted tubule. But surrounding that long loop of hennelly. That blood vessel network is called the vasa recta. Cool. Now let's talk about how urine is actually formed. Part two the process of urine formation. Ooh, we're making good time. Okay. All right. So there are three basic processes that are involved when we form urine. The processes are called glomerular filtration. That's the first thing that's going to happen. Then we have something called tubular reabsorption. And then we have something called tubular secretion. And we're going to go through each one in detail. So the first step that we need to tackle when forming urine is glomerular filtration. As you can probably imagine, where is this going to happen in the Lamarre Alice. Right in that collection of capillaries. So glomerular filtration. This is our very first step in forming urine. And so what we can see here in this picture is we have, you know, one of those smaller arteries that branches deep into that renal cortex. The afferent arterial, remember that's the blood vessel that's going to feed into the amaryllis. So the glomerulus is a collection or a tuft of capillaries. We call them glomerular capillaries here. This is the blood or I should say the blood in these capillaries is what we're going to sort through. We're going to look through see what we want to keep, what we want to filter out. And then that blood is going to leave the glomerulus, and it exits here through this efferent glomerular arterial. And then that blood vessel network is going to surround the rest of the nephron tubule. Okay. So first step, we are going to be pushing things out of these tiny capillaries into the surrounding Bowman's capsule. Right. That double World Cup that's going to catch whatever we filtered out. What things are we going to filter out. We are mostly going to be filtering out into Bowman's capsule. These smaller components of the plasma. So think. Hmm, can't even really see that water. Water is a big one. Let's do it. And white. Hopefully it'll show up. Water. We're going to filter out ions. Like sodium. Potassium. And chloride. And then we're also going to be pushing out some smaller waste products that we don't need. And so as it states in the slide, you know, what is it that we're filtering out. It says protein free plasma. What does that mean. Well, we know that in blood as a whole we have red blood cells. We have larger proteins. So any kind of molecule or component in our blood that tends to be larger, like bigger proteins or red blood cells, that's going to stay behind, that's going to stay in the capillary that does not get pushed into Bowman's capsule. Only the really small things are able to get through. So again this type of filtration only happens in the glomerulus. And what's cool to know is that out of all of the blood that enters the glomerulus, only 20% of it actually gets filtered into Bowman's capsule. So it's not a lot that we're pushing out. It's only 20% of all of the plasma that entered. And then we already answered this question in the bottom. What is being pushed out of the glomerular capillaries and into Bowman's capsule? We said water. Small islands. Like sodium. Potassium chloride. And other small waste products. All right. How do we feel about that so far? We're pushing things out of the hold. One of the smaller components that'll fit into Bowman's capsule, and Bowman's capsule is catching it like a catcher's mitt. Almost. More so being at home, filtering 20%. Part of that has to deal with the pressure, the size of the capillaries, how big they are, surface area. Uh, but if I was to generalize it to one thing, I would say size. Size of the of the collection. All right. So that's the first step. Informing urine. Actually, before I move on to that, I want to emphasize one more time what are things that we want to leave behind? Things that we want to leave here in the glomerular capillaries that will then exit through the efferent arterial. What staying behind red blood cells, larger proteins or just anything that's bigger in size. Okay. That was the first step. Next step in forming urine is called tubular reabsorption. Okay. So we've successfully pushed some things into Bowman's capsule. We now call that fluid filtrate. Once it's in the tubular component that filtrate is then going to continue along down the path of the other parts of the nephron. So it's going to be pushed into the proximal convoluted tubule. Then the loop of hennelly then the distal convoluted tubule. And so when fluid is in the tubular component, remember our bodies are preparing to let that go in urine. But the thing about glomerular filtration is that it's not that great at filtering stuff. And so we need another way to help fine tune what ends up being excreted out of the body as a urine. So that's where tubular reabsorption comes into play. So as filtrate is flowing through the rest of the tubule, there could be things that are in the tubule that we actually want to hold onto that we maybe don't want to get rid of. So tubular reabsorption is the process in which something that's in the tubule is going to be moved back into the bloodstream. It's going to be moved back into those Perry tubular capillaries that surrounded the entire nephron. Reabsorption. I want you to think your body has decided to hold on to it. You are re absorbing it. This process is selective, so you are choosing what you want to hold on to. So it's the selective movement of substances from inside the tubule back into your bloodstream. Those reabsorbed substances are then going to return back to your general circulation. So that's the second step. We call that tubular reabsorption. Think of things like, um, aliens or we are going to talk about that. I have a whole list of things that you guys will need to know what gets reabsorbed. Okay. The other way that we fine tune here, and this is just the third way, we call it tubular secretion. Now, this is the opposite, okay. Because remember, the glomerulus only filtered about 20% of the blood that came in through that collection of capillaries. Sometimes you leave things behind in the blood that your body's like, oh wait, no, I actually really don't want to hold on to this. I want to get rid of this in the urine. So that's step three. That's tubular secretion. So it's the selective transfer of substances. From the bloodstream. Into the tubule. Your body is saying, yeah, I'm ready to get rid of this. And so this is the second way that substances can enter the tubules from our bloodstream. This is the second route. That first route was glomerular filtration. Okay, so this is the direction in which things are flowing. So here's how I remembered this. Tubular secretion is the movement of things from your blood into the tubule, because you want to secrete these things out in your urine. So these three processes are going to help us form urine. And we're going to go through each process in painstaking detail in each part of the nephron so we can see what's happening. So step one, how is blood first filtered into the glomerulus? Okay. So this kind of relates to Kim's question why is it only 20%? Well, the anatomy and the size of the glomerulus is going to impact what is being filtered. Okay. So the anatomy is going to Matterson is the size. And that's because we have a pretty sophisticated filtration membrane that surrounds the glomerulus that's going to decide what things are being pushed out of the capillary and into Bowman's capsule. And so we have a little barrier. Let's zoom in on this. So this is our glomerulus. Right here we have our afferent arterial that's bringing in unfiltered blood into the glomerulus. The glomerulus is this collection of capillaries. And then blood can leave the glomerulus through that efferent arterial. Surrounding the glomerulus. We have Bowman's capsule. All right. So MaryAlice forms a barrier that's going to decide what particles are able to go from the inside of the capillary into Bowman's capsule. So the barrier includes the actual lining of the capillary itself. So the glomerular capillary has gaps in it which we call fenestration. So it's spaces in the actual blood vessel itself. So that's the first part of the barrier. Then we have another basement membrane that's going to be directly outside of the blood vessel. And then the third barrier is, you'll notice that there are these funky looking cells that sit on top of the glomerular capillary. These cells are called poteau sites. And they look like little feet. Right. Because poto means foot. And so these poteau sites are going to sit on top of the capillary, and they're going to leave little spaces in between them. And so we're going to have little slits that form little openings that can allow particles to be pushed into Bowman's capsule. So all three of those components are going to form our filtration membrane, which are the barriers that fluid and particles need to get through in order to make it into Bowman's capsule. Okay, so like I said, the lining of the capillaries themselves have holes in them or fenestration. There's a basement membrane involved. And then there are filtration slits between those adjacent sites, which I'll show you in a different slide. Here we go. Okay, so this is zooming in to what's happening in the amaryllis. So here on the left we have our glomerular capillary. So the capillary contains your blood that has not yet been filtered. So again what does blood have. Blood has red blood cells. Water. White blood cells. Waste hormones. So many different things in it. You'll notice that the blood vessel itself, the capillary, has holes in it. Right. These little gaps. So those holes are called fenestration. You could see those striations here. These Finnish stations are pretty small. Okay. So that's going to allow the larger things like red blood cells, large proteins or just larger molecules to stay in the capillary because they physically can't get through that gap. After that, we have this basement membrane in the middle. And then these guys here, these are the photo sites or the cells that sit on top of the capillary. And the way that these poteau sites sit on top of the capillary, they leave a tiny little space in between adjacent poteau sites. And we call those spaces filtration slits. And then what's hanging out surrounding that will now you're in Bowman's capsule. You have made it to the tubule. So you can see that there's some hurdles that these particles need to get through in order to actually make it into Bowman's capsule. So what things stay behind in the capillary. Again red blood cells. Large plasma proteins that are in the blood like albumin. Globulins. Large anions, um, hormones that are bound to proteins. Uh, pretty much anything that's greater than eight nanometers. It's going to stay behind. But the things that actually make it through the barrier are smaller particles. So what passed through that filter? Water. Electrolytes like sodium. Potassium chloride. Glucose is small enough to get through. Uh, amino acids, fatty acids, vitamins and small waste products like urea, uric acid, and creatinine. All right. So that's the first thing that you have to consider when you think about glomerular filtration is can the thing actually get through. The next thing you have to think about is what's the motivation to be pushed into Bowman's capsule? So glomerular filtration is heavily reliant on the blood pressure inside of the glomerular capillaries. Okay, so there are a few different pressures that are going to be at play here. So here in my drawing. Just kidding. I did not draw this. I traced it. I wish I drew it, but I did not. Um, so this is our apparatus. Right here we have our afferent arterial bringing in unfiltered blood into the glomerulus, which is our collection of capillaries. Once blood has been filtered, it leaves through the efferent arterial and then surrounding the amaryllis, we have Bowman's capsule that's catching that water and those electrolytes. So our first pressure is denoted by this blue arrow. And that's called the glomerular capillary blood pressure. I tried to color code things. So this is the pressure that's exerted by the blood in the amarilla capillaries themselves. Right. Because all blood vessels have pressure to them. They have a blood pressure, which is the, you know, motivation with which blood is flowing through the vessel. Higher pressure, the more motivation there is to push that blood through. Now typically this pressure is 55 mgs, which is I mean, that's pretty strong for the glomerulus because those capillaries are so tiny. And so this is the pressure that's actively pushing plasmas, water and solutes out of the glomerular capillaries and into Bowman's capsule. So think of it. This is the driving force that's actually pushing those things out. So again, this is, um, a relatively high pressure for such tiny capillaries. And then what I also want you to notice is notice how I drew the afferent arterial larger than the efferent one. That was not on accident. That was intentional. And that's because the diameter of the afferent arterial usually is bigger than the efferent arterial. But we can manipulate that. Okay. So again what is driving filtration. What is pushing water ions out of the glomerular capillaries and into Bowman's capsule. It is this glomerular capillary blood pressure. We're going to play around with this later on. And I shorthand it to GCB BP. Okay. So make a note of that. That's going to come back JK BP is equal. Marylou. Capillary blood pressure that is actively driving filtration. And how do we know it's favoring filtration? Because it's favoring the movement of particles into Bowman's capsule, which is indicated by this arrow. All right. The next pressure that is going to impact filtration is called the plasma colloid osmotic pressure. We actually talked about this before in a previous lecture. And this had to deal with proteins right. So when we talked about this in a previous lecture, I said, you know, water follows salt by principles of osmosis, right? Water also likes to follow big proteins. Water likes big proteins and it cannot lie. So, uh, let's think about how this works. What are we leaving behind in these glomerular capillaries? What did I say? Does not get pushed out into Bowman's capsule. What are some things? You can also refer to the previous slides if you need to. Red blood cells and what else? Big proteins. Right. So what we're leaving behind as we're doing glomerular filtration is we're leaving big proteins in these capillaries. What did we push out into Bowman's capsule? A lot of water. So what happens is water in Bowman's capsule sees the big proteins that are left behind. And it's like, wait. I kind of want to go back. I kind of want to be where the proteins are, right? And so then this is a tiny pressure, the plasma colloid osmotic pressure, where water kind of wants to go back a little bit. It's a very, very small pressure. But it does exist. And it does oppose filtration. Okay. So this pressure is the tendency for water to move where there's a lot of proteins. We left a lot of proteins behind in those capillaries. This pressure opposes filtration because water wants to go back. And this pressure is typically 30 mgs. This stays pretty constant most of the time, but it's just something that happens because we're dealing with water and proteins. And that's denoted by the pink arrow here. All right. And then our third pressure that's involved is called Bowman's capsule hydrostatic pressure. Basically what this says is as we've pushed out water, solutes, waste products into Bowman's capsule, Bowman's capsule starts to get full. Right. And so what happens here is all of the components that have been filtered. They push back a little bit on filtration because they say, oh, we're full. We don't need any more water. We don't need any more salt in here because we are reaching capacity. So it's a tiny, tiny, small, small pressure that does inhibit filtration a little bit. So all of the water and solutes that are in Bowman's capsule already give a little pushback. It's like, no, you can't come into Bowman's capsule because I'm here. And so that's denoted by that small purple arrow. And again that pressure is small. Okay. It does oppose filtration. And it's typically 15 mg. It also is usually pretty constant. So let's think about this. Okay. We have three pressures involved. One favors filtration, favors the movement of water and solutes into Bowman's capsule. The other two do not. Let's think about this. If a pressure favors filtration because that's what we want. We want to make urine. We are going to give it a positive sign. If a pressure opposes filtration, which we don't want, we are going to give it a negative sign. All right. So we know that the glomerular capillary blood pressure favors filtration. And it's usually 55 mg. Right. Because we're thinking about all of the pressures involved. All right. Actually, no, let me not do parentheses because then this is going to get weird. Okay. Now we had the plasma colloid osmotic pressure which opposed filtration. So we're going to give it a negative sign. And that was 30. Amaechi. Actually, no, I will do a parentheses. And then we had our Bowman's capsule hydrostatic pressure which also opposed filtration. So we'll give it a negative sign. And that one was 15. All right. So we have a pressure that favors filtration. That's 55 mg. 30 and 15 together make up 45. MMR HG. So in total there is a pressure of 45 MGS that oppose filtration. So taking this into account, what we end up with. Is a ten m m h g pressure. That is favouring filtration. So out of all of the pressures combined, what we get at the end, the one who won the fight was the favor of filtration. But that pressure was a little bit smaller now because we had to take into account the other two that were fighting. So what this tells us at the end of all of this is that 20% of the plasma that entered the glomerulus is going to be filtered, pushed out into Bowman's capsule at a net pressure of ten mh gs that favors filtration. I'll stay here for a second. Does that make sense? Okay. Hello. All right. So. The pressure then in the glomerular capillaries is essential. That's going to have a huge impact on what you filter and how quickly you filter it. Now there's another component to glomerular filtration. We call it glomerular filtration rate or GFR. Ah. So GFR is basically the rate in which blood in the glomerulus is being filtered into Bowman's capsule each minute. So it's basically saying how quickly are you pushing blood out of the capillary into Bowman's capsule? So that's GFR. It's rate. It's speed. Okay. So GFR is dependent on three things. The major thing that's going to impact GFR. You guessed it is the filtration pressure. Okay. So the glomerular capillary blood pressure is going to impact GFR. Now let's think about that. For a second. So glomerular capillary blood pressure is the pressure inside of these vessels. We know that there are other pressures involved, but we are getting a net filtration pressure. Of ten mgs. And the speed with which we are collecting things in Bowman's capsule and moving it on to the other parts of the tubule that's going to be impacted by how quickly things are being pushed out of the capillary. And we're going to play around with this. So the major determinant of GFR is the glomerular capillary blood pressure. We are going to see ways that we can manipulate the glomerular capillary blood pressure. And how we're going to do that is by manipulating the diameter of the afferent arterial. There's other things that are going to affect GFR, like the surface area of the glomerulus or how leaky or holey the glomerular membrane is. But these last two things are pretty constant. We we really can't change those. So the major factor that is going to impact GFR will be glomerular capillary blood pressure or GC BP. So what you should take away from this slide is that. GFR, so rate depends on pressure. And you'll see why. So what the kidneys can do. The kidneys are so smart they can adjust the GFR. At any given moment. They're constantly adjusting GFR depending on what your body's doing right, what your blood pressure is. So what it's adjusting is the rate or effectiveness with which blood is being filtered in the memory lists. So let's lay some ground rules before we start to manipulate things. If your glomerular filtration rate is too high. What that means is that you are pushing out a lot of things into Bowman's capsule. Think of it as you're just carelessly and quickly just going here. Bowman's capsule, you get all the water, you get all the salt, and then Bowman's capsule is getting a lot of water, salt and waste and like, oh, okay, then let me hurry up and push it to the next place. So when GFR is really high, that creates this sense of urgency and carelessness in the kidney. So fluid aka that filtrate is then going to flow through your tubules too quickly to rapidly. So your kidney doesn't even have time to reabsorb or retain the things that it needs to. So the kidney is not. Taking the time to reabsorb the things that it wants to. So what this means for the person is that their urine output increases, so they are going to urinate more frequently. What's in their urine? A lot of water and a lot of salt. Because the thing about the kidney is that we actually, out of all of our blood that gets filtered, we retain 99% of our salt and like 87% of our water. So we actually hold on to most of our water and our salt. So if GFR is too high, we just urinate everything out and we don't want that because that increases your chances for becoming dehydrated. You lose a lot of those ions in your urine that you need. So you get electrolyte depletion. Now that's if your GFR is too high. You don't want that. If your GFR is too low, that could also be a bad thing. And let's think about it. The opposite happens. If your GFR is too low, your kidney is in chill mode because things are moving slowly. So when your GFR is low, the filtrate is going to move through the tubules to slowly. And when the filtrate moves too slowly, what ends up happening is you start to reabsorb waste products that you normally would want to get rid of. And this could cause something called azo tinea, which is when you have really high amounts of nitrogen and waste in your blood because you reabsorbed it when you were not supposed to. And here's my analogy for a low GFR. You know, at these stores like Sephora and Ulta and Target. What's near the checkout line? What do they have? They have candy, they have a bunch of little things that you don't need, but that it's so easy to go, oh wait. Yeah. Okay. Let me add that on. If you are in a line, let's say you're shopping and let's say that the line is taking a longer time, like you're standing there for a longer period of time. I don't know about you, but I'm more tempted to look at what's next to me, and I'm more inclined to buy things that I actually don't need. Right? Because I'm like, oh wait, that's cute, should I okay, yeah. Why not? Right. And so that's what the kidney is doing. If the fill treats moving too slowly, the kidney sees all the waste and the blood supply is like, should I. Yeah. Okay. Let me reabsorb that waste. Maybe I actually really want it. So that's the same thing here. Think about the checkout line. If you're moving through a checkout line pretty quickly, or let's say you're doing some shopping and you're moving too fast, you're not consulting your list. You're more likely to forget something when you're moving quickly. You don't give yourself time to check. Okay. What did I want to buy? Did I get everything? And you leave the store and you're like, oh, I forgot to buy x, y, z, whatever. Yeah. And so how are we going to regulate GFR? Well, we are going to manipulate the thing that impacts GFR, which is the glomerular capillary blood pressure. And we manipulate that all the time. And GFR will be regulated by two key mechanisms. Uh which we'll talk about. Hormones are going to play a role. And then there's an auto regulatory effect. All right. We're going to do this part. Then we're going to take a break. So let's let's manipulate this. So if we want to adjust GFR, what we really want to change is the glomerular capillary blood pressure. Right. Because that's the thing that affects heart rate is affected by pressure. All right, let's think about this. So. When you constrict the afferent arterial. We can see that here. We've constricted it. What happens to the diameter of the blood vessel when you constrict it? Did it increase or did it decrease? Feel free to shout it out. The diameter. Oops. Decreased. Beautiful. Okay. All right, let's think about our blood flow lecture. What happens to the resistance in a blood vessel when you reduce? The diameter. Is it harder for blood to flow through a vessel that's smaller? It is, right? So the resistance to blood flow is going to increase. Exactly. Okay. When there's a lot of resistance to blood flow. Is blood flow going to increase or decrease if there's a lot of resistance and a lot of opposition? Blood flow decreases, right? Because resistance is opposing blood flow. Okay, so what this means is that there is less blood flowing into the glomerulus. When we did that. When there's less blood in these capillaries, what do you think's going to happen to pressure when there's less blood available? Pressure is also going to go down because you're letting in fewer milliliters of blood. So the glomerular capillary blood pressure also decreases because you're letting in less blood. All right. Now, if there's a lower pressure in these capillaries. Do you think GFR is going to be super high or is it going to also go down? What do we think? It's also going to go down right. Because Flo or I should say pressure and GFR go hand in hand with each other. When the pressure is lower right, the line is slower. The glomerular capillary blood pressure is also going to be slow. Right. You're slowing things down. There's no rush. So glomerular filtration rate will be lower. Or we could say it decreases. So through this afferent arterial or vasoconstriction. We slowed things down. How did we slow things down when we just let in less blood? And that forced us to kind of like take a step back. All right, now let's try the opposite. Let's say that we dilated. The afferent arterial. When you dilate that afferent arterial, what happened to the diameter? Did it increase or decrease? Yes. It increased. All right. When we have a bigger blood vessel. What happens to resistance when there's more space? Exactly. So resistance decreases. When there's less resistance, what happens to blood flow? It increases, right? Because resistance makes it harder. So when there's less resistance, it's easier for blood to flow. I like that. All right, so we are bringing in more blood into the glomerulus. So if we're bringing in more blood, what do you think is going to happen to the capillary blood pressure. If we're bringing in more. It's also going to increase. What do you think is going to happen to GFR when we have high blood pressure, where we're creating a bit more of a frenzy? GFR will also increase. Does that make sense? Perfect. So here what we're doing is we are speeding things up. So filtrate is going to be pushed into the tubule at a really high speed. All right. So this is glomerular filtration in a nutshell. This just really describes what we've been talking about. What is being filtered. Basically everything that's in the plasma that can fit. Except for large proteins. So what is then going to be found in the filtered fluid in Bowman's capsule? So we are going to have some waste products being pushed in there. We have things being pushed in there, materials that the body doesn't have a receptor to reabsorb, like drug metabolites. If you took an Advil or an aspirin or something. But we are also going to push into Bowman's capsule some materials that our bodies cannot afford to lose, like nutrients and electrolytes and water. So we have filtered some things that we actually want to hold on to. How are we going to reclaim those things through tubular reabsorption? So this is the very first step to all of this. Your information. And so this chart just summarizes what I said. All right. So with this we are going to take a five minute break. We'll come back at 1027. And we'll pick up the rest of the lecture. All right. So we just covered in the first step in your infiltration there are two other processes. And then we have 1234 for regions of the kidney to get through. So the important thing to keep in mind when we're forming urine is that we actually want to hold on to most of the things that originally get filtered in legal, memoryless. So the overview of your information is that 99.5% of all of the sodium that was initially filtered out in England, Mary Alice gets reabsorbed. So our bodies actually want to hold on to 99.5% of the salt that was pushed out in these Lake Mary lists, 67% of that salt is going to be reabsorbed in the proximal convoluted tubule in the PCT. 25% will be reabsorbed in the loop of Hennelly. An 8% will be reabsorbed in the DCT and in the collecting duct. Okay, so you can already see that the bulk of sodium reabsorption happens in the PCT. And then another huge component that I said gets filtered is water. And we retain 80% of all the water that was filtered in the glomerulus. So that gets reabsorbed. 65% of that water is reabsorbed also in the proximal convoluted tubule. Whereas 15% gets reabsorbed in that loop of Henley. Now what you can see here. This chart highlights the things that get reabsorbed and secreted in each of these regions. The things that are color coded in blue represent all of the things that get reabsorbed or retained by the Perry tubular capillaries in each region. Everything in pink represents the factors that get secreted by those Perry tubular capillaries back into the tubule. So the things in pink are the factors that are going to be eventually excreted out as urine. All right. So let's start with that proximal convoluted tubule. So the proximal convoluted tubule reabsorb 65% of all of the salt that was initially filtered. How does it do that. So this picture here shows us this. Here on the right would represent the inside of the PCT. So all of the fluid in here would be the filtrate. The stuff that would eventually get excreted out as urine. And then remember I said that the tubule is made up of a single layer of epithelial cells. So these are the cells that form the lining of the tubule. They're pretty small. They're pretty thin. They're ideal for diffusion. And then surrounding the tubule, we have the extracellular fluid called tissue fluid. We also call this interstitial fluid as well. Or you could think of it as the ECF. Right next to that ECF, we have the Perry tubular capillaries that are eventually going to go back and form the renal vein. So these are things that our bodies will hold on to. All right. So the first step here is a type of trans cellular transport. So that's when we are going to be moving factors across the epithelial cell into the Perry tubular capillary. Right. Because this is reabsorption. And so let's view some things that we're really absorbing. So this side of the epithelial cell is facing the inside of the tubule facing the inside of the PCT. So one of the first transporters that we use is a sodium glucose sim Porter that we learned about at the very start of the class. And so the sodium glucose in Porter is going to push sodium and glucose out of the tubule into our at the filial cell. Glucose will then be transported back into the bloodstream through this glucose transporter or glute. That's just facilitated diffusion. So we are transporting glucose back into the bloodstream. The next thing that we are transporting is sodium predominantly. So we transport that through a sodium hydrogen, um, ante port, where we bring in sodium into our epithelial cell and kick out a hydrogen ion back into the tubule. Sodium is then pushed out into the Perry tubular capillary. You are sodium potassium pump. Okay so the sodium potassium pump kicked out three sodium ions. So it's kicking out three sodium into the bloodstream and bringing in two potassium into our cell. Okay, so what did I just say? I said that we pushed glucose and sodium back into the Perry tubular capillary. We also have a chloride anion anti port as well. So we are going to push chloride into our cell. And then we have a potassium chloride some water that pushes potassium and chloride. Into the bloodstream. And then we have water channels are aquaporins. That transport water just directly across the cell. So water will also get back into the Perry tubular capillary. That's H2O. All right. So what did we reabsorb here. We reabsorbed glucose sodium potassium chloride and water to all of those different pumps and channels. And that's just across the cell itself. We have another way to reabsorb stuff, which we call para cellular transport. So para means near. So this transport happens in between our epithelial cells. So this is how we move particles in between our epithelial cell lining. So what are some things that we are pushing through Paris Cellular. We are going to be pushing through things like water. Waste products like urea uric acid. And then we're also going to continue to push ions like sodium, potassium chloride, magnesium, calcium phosphate. So we are just continuing to push water and solutes aka ions into the blood here. We call that a solvent drag because we are moving ions just in between the cells. They're being dragged. So that's reabsorption in the proximal convoluted tubule. But we're also going to be secreting certain things here as well. So again tubular secretion is a process in which chemicals are extracted from the blood supply. And pushed into the tubule, so we get rid of it as urine. So what are some things that we are secreting into the tubule in the PCT specifically? Well, we are going to remove any waste products that were maybe left behind in the peri tubular capillary. Um, so again, things like urea, uric acid, bile acids, which is a remnant of digestion, which we'll talk about next week. Ammonia some creatinine basically metabolites byproducts of life. Uh, we're also going to clear the blood of any pollutants, any drugs like morphine, penicillin, aspirin, anything that we may have taken. And then we also are going to secrete hydrogen ions into the tubule to help regulate the pH of our bloodstream. If it becomes too acidic. Right? Because if something is acidic, it has a lot of hydrogen in it. So we could maybe get rid of those hydrogens in the urine. Okay, now on to the loop of Henley. So this loop dips far into the renal medulla. And just if I was to summarize it in one sentence, I would say that the loop of Henley's function is to make our urine concentrated. What that means is through the loop of Henley, we want to reabsorb a lot of water and a lot of salt. So that way the urine only contains waste. We want our urine to have as little water and salt as possible, because we need water and salt for other processes. So the goal, what we're going to accomplish here is we are going to create a saline gradient, a salt gradient that's going to help us conserve water and salt. So that way our urine mostly has waste in it. And so this is our loop of Henley again. It dips down into that renal medulla. I told you that the renal medulla is a salty place. And that will make sense in a bit. And something that I want to mention is how we can express the concentration of urine that's going to be through milli osmosis. Okay. Lowercase m capital o. And then S.M.. So million dollars. Most represents how concentrated a solution is, which basically says how many salts are there? Given how much water is in the solution. So let's take two solutions. Let's say we have a 900 milli Osmo solution and then a 100 million small solution. Which one of the two would you take to be the more concentrated one? The 900 or 100. 900, right? Because the 900 says you have 900 salutes in how much water there is versus 100, you would only have 100 salutes. So here 900 would be the more concentrated solution. All right. So. When the filtrate first enters the loop of Henley, it has a concentration of about 300ml moles per liter. That's okay. Right? It's not super concentrated. Um, but it's not like 100 either. Okay. And so what we're going to notice is that the descending limb of the loop of Henley is only permeable to water. Now remember I said this medulla. This surrounding area is super salty. Water loves to follow salt. So if you principles of osmosis in this descending limb water is like by I am leaving the filtrate. I want to go to the salty medulla. So water is going to leave the filtrate down this descending limb. So then what are you leaving behind in the filtrate? You're leaving behind a lot of salt and a lot of waste. So as the filtrate dips down into that descending limb of the loop of Hennelly, the filtrate becomes more concentrated. Look, now it's at 1200 milli moles all the way at the bottom. There's good and there's bad to that. Remember I said that we actually want to hold on to the majority of our salt. If we were to urinate this out as 12,000, there'd be a lot of salt in there that we want to hold on to. Now, the ascending limb of the loop of Hanley is only permeable to sodium and chloride. So through a process called counter current multiplication, NaCl is going to leave the tubule and be reabsorbed by the Perry tubular capillaries. So as NaCl are leaving the filtrate as we go up the loop of Henley, what you'll notice is that the filtrate starts to become less concentrated. So what are you leaving behind in the filtrate? Just the waste now. Just the things that you actually want to get rid of. Maybe a little bit of salt, but mostly waste products. All right. Again. The thin descending limb of the loop of Henley is only permeable to water. Whereas the thick ascending limb is going to help us reabsorb about 25% of sodium chloride. All right, let's go through that again. So this right here is a simplified drawing of our loop of Hanley. We have the descending limb and then ascending limb. Now let's think about the surrounding tissue. The surrounding tissue is the middle of the kidney. We call that the renal medulla. So I will color that in salmon. Now the renal medulla gets saltier and saltier the further down you go. So here this portion would have a concentration of 500ml moles per liter. Then it increases to 700 and then 900. So the point is that you get saltier and saltier. The further down you go the concentration gets higher. There are more salts then there are water molecules here. Surrounding the loop of Henley. You have capillaries. Right either the Perry tubular capillaries or the VA's erector. Here. We'll just say, Perry. Tubular capillaries. All right. So we have two things going on here. We have a salty tissue. We have our blood supply that's surrounding the loop of Henley. This entire process of how water and salts move in the loop of Henley is called counter current multiplication. So it's basically a process in which we created this vertical osmotic gradient. So the fact that the medulla gets saltier and saltier the further down you go. That's going to drive. The reabsorption, the retention of water and salt NaCl. This is going to help us form urine that is concentrated and contains mostly waste products, and it allowed us to reabsorb most of the water and salt. All right. So let's go through this counter cream multiplication. So the filtrate when it enters the descending limb of the loop of Henley, it has a concentration of about 300 million moles per liter. Okay. Now what counter current multiplication says is as this filtrate goes down further into the medulla, remember that tissue gets saltier and saltier the further down you go. In the descending limb of the loop of Henley. Only water is moving. Water is going to follow principles of osmosis, and it's going to diffuse into. That Perry tubular capillary until the blood and the tissue are equal, until they equilibrate. So what happens is water is going to be pushed into those capillaries that surround the loop of Henley, such that the filtrate is going to be equal concentration to how salty the renal medulla tissue is. So water continues to be reabsorbed as we get further down the descending limb. The actual filtrate gets saltier and saltier because we left behind nothing but the salt. All right. So again I'll just leave it at that filtrate becomes more concentrated the further down you go. Now the counter current multiplication also says is as that filtrate is coming back up through the ascending limb. It wants to create a 200 million Osmo per liter difference between the medulla interstitial fluid, which is this like salmon shaded area, and then the actual filtrate itself that's in, uh, the tubule. And I'll show you how it does that. So at the bottom of the loop of Henley, the filtrate is highly concentrated. It has a concentration of 1200ml moles per liter. Now along the ascending one, the ascending limb is only permeable to sodium chloride and potassium. Because here is what happens. So along that ascending limb of the loop of Henley. We are going to find a bunch of these sodium chloride potassium transporters. And of course, we have our blood supply surrounding the entire thing and our salty medulla. All right, so what happens through this transporter? Sodium. And chloride are going to be pushed into the Perry tubular capillary that surrounds the nephron loop. And potassium. Is going to be secreted into the tubule. So this transporter is pushing NaCl in the same direction and potassium in the opposite direction. Okay, so here it says that the sodium chloride potassium cotransporter pushes NaCl into the vasa recta. Actually, yes. This specific blood vessel network around the longer loops of Hennelly. We'll just say it's the vasa recta. And we push out enough NaCl until there's a 200 million mile per liter difference between the fluid and the medulla interstitial fluid. So if the medulla has a concentration of 700 million moles, we will push out enough NaCl until the filtrate has a 200 million small difference, which would make it 500 million moles. Okay. And then I mentioned that potassium is also being secreted into the tubule. And so then what are we leaving behind in the filtrate as it gets further and further up the loop of Henley? We get urine with not as much salt in it. It has mostly waste products. Uh, so we're really fine tuning just how concentrated urine is. So an overview of this in the loop of Henley. The descending limb is only permeable to water. So we are going to reabsorb water back into our bloodstream down the descending limb that leaves behind mostly salt in the filtrate. So the filtrate gets more and more concentrated the further down into the lipase. Finally you get. The ascending limb is only permeable to NaCl and potassium, and NaCl is going to be reabsorbed back into the bloodstream through this NaCl potassium transporter. NaCl and potassium. And then as that's continuing to progress. The filtrate becomes less and less concentrated because we're holding on to all that sodium and, you know, chloride. So what we get at the very end is filtrate that has mostly waste in it, which is good because we want to retain most of our salt and most of our water. And so this chart here on the right does describe what's happening as well. Uh, I will not test you. So the chart talks about active transport versus secondary active transport. I will not test you on those details, but instead I want you to know everything else which we went over verbally. I want you to know what's being reabsorbed and what's being secreted here. In the loop of Henley. So again, the types of transport. I don't want you to worry about that. All right. Does that make sense? Okay. Counter current multiplication. I didn't tell you guys this before we started talking about it, but it's one of those things that haunts physiology students because it sounds a lot scarier than it is. So I have like my favorite video ever, but I'm going to play a single clip of handling and the way it helps to concentrate urine in the kidneys. The loop of Henry is found between the proximal convoluted tubule and the distal convoluted tubule in the nephron. There are actually two types of nephron in the kidney cortical and just in medullary. This happens to be a gypsum medullary next one. Because of its lonely posteriorly and the fact that it dips down into the medulla of the kidney, this type is well-suited to the role of helping to concentrate urine. As discussed in my function of the nephron video, filtrate moves through the tubules and eventually exits the collecting duct as urine. But what we want to know is why does the concentration of filtrate increase as you go further down the loop of osmolarity is the concentration of a solution often expressed as merely osmosis. Peter filtration. The proximal convoluted tubule has a osmolarity of 300 million osmosis per liter, the same as the surrounding interstitial fluid. This means that the filtrate is either osmotic with the surroundings, but it's a very different story in the loop handling. Let's zoom in. Let me give you a brief recap of what happened here. But if you want more details, including information about permeability, do go back and watch my previous video. Okay, so in the thick ascending limb, sodium ions are pumped out and negative ions such as chloride follow, making the medulla a quite concentrated and salty region. Water these passively from the descending limb because of the surrounding salty environment. And as the water leaves infiltrating, the descending limb becomes significantly more concentrated. In addition, the salty metal is also a major reason why water is able to move passively out of the collecting duct and be reabsorbed back into the blood source, leaving behind more concentrated urine. But let's pretend that the fluid traces entering the loop of handling for the very first time. Naturally, because the filtrate is coming from the proximal convoluted tubule, it will have the same 300 milli Usmle put into it as the narrative, and the eyes are osmotic with the interstitial fluid. However, this situation is not ideal for creating concentrated urine. So in the latter part of the loop of healing, our aim is to create a difference of 200 million Osmo per liter between the ascending limb and the interstitial fluid. The only way to do this is by pumping out sodium ions. So let's pump. As you can see, the osmolarity in the ascending limb has decreased due to a loss of sodium, whereas in the interstitial fluid it has increased due to a gain of sodium. And if you look closely at the values, you will see that we have achieved the 200 million or more per liter difference, otherwise known as a gradient. But what's happening with the descending limb? Here the filtrate needs to equilibrate, meaning that the water will leave passively until the filtrate in the descending reaches the same osmolarity as the interstitial fluid. Time to equilibrate. Note equilibration does not change the osmolarity of the interstitial fluid to treat moves through the nephron continuously. But I'm going to break this down into steps for you. Let's advance the fluid in the loop of handling. When running 300 million or more per liter filtrate enters the descending limb from the proximal convoluted tubule, and filtrate already in the loop of handling is pushed further along, bringing back our values for the interstitial fluid, we see that our gradient has been messed up, so we need to reestablish the ideal 200ml more per liter difference. Let's pump house and surgeon ions. Okay, although the values vary, there's still a difference of 200 at all levels, so we're content not to equilibrate the descending limb of the interstitial fluid and advance to treatment in the loop of Henle. A little low and behold, the gradient is messed up again. But we know what to do. Let's pump and establish that 200 milli Osmo per liter gradient equilibrate to much osmolarity and advance the fluid. Okay, one more time to get the point across our gradients is messed up. Pump out sodium to restore the gradient and equilibrate. All right. So looking at our values for the interstitial fluid we can see that the osmolarity increases the deeper you go into the medulla. As all that pumping and equilibrated continues we eventually reach a maximum concentration of around 1200. The utmost burrito. The entire process that I have just described is called counter current multiplication counter current, because the filtrate flows in opposite directions in the limbs of the loop of handling and multiplication. Because this counter current flow enables the effects of the gradient to be increased, i.e. applied. So in summary, the loops of Henle objects to medullary nephrons are involved in the process of counter current multiplication, which enables the interstitial fluid to become more concentrated, i.e. increase in osmolarity. The deeper you go into the medulla, the high concentrations in the middle the facilitate the passive movement of water out of the collecting duct and result in more concentrated urine. Okay, hopefully this tutorial was helpful to you. If so, don't forget. All right. I love that video. I like the illustrations. Now, I know you're probably thinking, am I going to have to write all those numbers and describe all of that? No. But the key takeaway that I want you to know from this is what's moving in each part of the loop of Henley. Right? Which part is permeable to water? Which part is permeable to salt? And then what's happening in each region? So as you go down the descending limb, the urine is becoming more concentrated. And why as you ascend, the filtrate becomes less concentrated. I want you to know why, and to know that the goal of all of this is to fine tune the filtrate. So it has mostly waste in it, because we're reabsorb being mostly water and salt here, because we want to retain that. We want to hold on to that. All right. Okay. So the fluid that is now in the ascending limb of the loop of Henley, it's now going to enter the distal convoluted tubule. And that collecting duct. So the fluid that has just arrived in the duct from the loop of Henley. Yes. We've concentrated urine. It has mostly waste in it, but it's not a perfect system because that filtrate now that's coming into the duct. It still contains 20% of the water and 7% of the NaCl from that glomerular filtrate. If you were to leave it as it was, if you were to leave the filtrate as it was coming out of the loop of Henley, uh, you would be urinating 36l of fluid per day. That's a lot of leaders, right? So the deceit and the collecting that are going to additionally fine tune that filtrate. So that way you're urinating not 36l. So both the DCT and collecting duct are usually considered together. I usually group them together. And here's what they do. Both regions are responsible for secreting variable amounts of hydrogen and potassium, AKA that means the Perry tubular capillaries that surround both areas are pushing hydrogen, potassium, and ammonium into the tubule to then be excreted out as urine. And then the DCT and the collecting duct are going to reabsorb variable amounts of water. NaCl and the DCT and collecting duct are subject to manipulation by three hormones that we're going to talk about. So both these regions, the DCT and the collecting duct, are responsible for re absorbing or allowing us to retain more water and more salt. And that's basically what's written here on this summary slide. But let's talk about the three hormones that are going to act on the DCT and the collecting duct and what they do. So the first hormone is Al Doster Rone, which we've talked about before. And when we first talked about it I just generalized and I said, you know it helps with sodium retention. Right. Think about that exam question. I was like, what is the function of aldosterone? Because I was prepping you for this moment. Right. When we think about what it is that this hormone is doing. So aldosterone is the salt retaining hormone. So it's a steroid that's produced by the adrenal gland that sits right on top of the kidney. It's made specifically by the adrenal cortex. And this hormone is secreted when the concentration of salt in your blood drops. Or for some reason, if the concentration of potassium in your blood skyrockets, like you've been eating too many bananas or something. So here's how it works. We're going to zoom in to the side picture here. This I did draw, so I'm very proud of this picture. Uh, what we see here on the left, this would represent the inside of the tubule, specifically the collecting duct and the distal convoluted tubule. This cell right here represents the epithelial cell lining that covers the tubule in the duct and collecting duct. And then this orange cell is a special type of cell that lines the duct and collecting duct, which is called principal cells. So these orange cells are special. And then surrounding the tubule, I have the Perry tubular capillary drawn to the side. So when aldosterone is secreted, this is how it works. Aldosterone is going to increase how much salt is reabsorbed in these two regions. Normally the duct and collecting duct are going to reabsorb 8% of the total that was initially filtered. But this hormone is going to make it so that we reabsorb more than that 8%. And it's going to do so by acting on those principal cells that line the collecting duct and the distal convoluted tubule. How does it do that? It's going to increase the expression of sodium leak channels on the side of the principal cell that faces the lumen of the tubule. So we are going to incorporate more sodium leak channels. So sodium will be motivated. To move from the inside of the tubule into the principal cell. This hormone is also going to incorporate more sodium potassium pumps on the side of the principal cell that faces the Perry tubular capillary. Again. What is the sodium potassium pump? Two. Why did I make you write an essay on it? Well, because now we know that this pump is going to push out three sodium out of the cell, and that sodium is going to go into the Perry tubular capillary. And then we are going to extract from the blood two potassium ions that are then going to go into our principal cell through that pump. And then aldosterone is also going to increase the expression of this potassium channel down here, which is going to push that potassium into the filtrate. So what you get at the end of this at the end of this hormone action? Is you get a lot of sodium in the blood. And a lot of potassium being excreted out in the urine. Okay now when sodium is being reabsorbed. Chloride likes to passively follow. So it's not just na, but it's NaCl being reabsorbed here. And like I said, aldosterone is also going to regulate potassium secretion as well. All right. And so I want you to know. This mechanism in the level of detail as it's written on this slide here. Know what channels are being inserted, where and what the outcome of that is. Right. So that's aldosterone. What is the outcome of this hormone. Well it stimulates the kidney to reabsorb more sodium and also passively because of that chloride. And this hormone is also going to stimulate the secretion of potassium into the urine. Water and chloride are going to passively follow sodium here. So if we're thinking about it specifically, aldosterone is directly manipulating the reabsorption of sodium only, and it's directly manipulating the secretion of potassium, water and chloride. That happens as a consequence. So I need you to know that distinction. All right. So then what is the outcome of re absorbing more NaCl. Well remember anything that's in the capillary gets kept by us right. It goes back to our general circulation our general bloodstream. So our bodies our blood will have more NaCl in it and more water. When blood has more water in it that increases the blood volume. How much blood we have. When we have more blood, our blood pressure goes up because we need more force to push that blood throughout our body. We will urinate less because we are removing water from urine and removing the salt. So you will urinate less and then whatever you do, urinate will have a lot of potassium in it. So that's Al Dawson, the other hormone that's going to manipulate the collecting duct. And DCT is antidiuretic hormone ADHD also known as vasopressin. All right. So how does this work. So antidiuretic hormone is going to make sorry just the collecting duct just the collecting that only more permeable to water. How does it do that? Well, this hormone vasopressin is going to insert more aquaporins or water channels on the epithelial cells that line the collecting duct. So these little dark navy circles are water channels. Called Aquaporins. Who? Cannot spell today. So it increases how many aquaporins we insert onto both sides of the epithelial cell. That's going to drive the reabsorption of water in the collecting duct. And so something to note is that diuretics are a class of therapeutic agents or medications that are going to cause diuresis, and diuresis just means to urinate to increase urinary output. And so a diuretic is going to promote fluid loss by the body. So someone is losing more water in their urine. So anti diuretic hormone does the opposite. It's going to cause you to hold on to your water. All right. So when does this hormone get released? Vasopressin aka antidiuretic hormone. Well. This hormone is produced by a neuron. In the hypothalamus. It was produced by a hypothalamic neuron in the supra optic nucleus. Of the hypothalamus. And so this hypothalamic neuron produces vasopressin and it releases it into the posterior pituitary. The hormone then goes out into the general circulation. So unfortunately. For y'all love it for me because I love hormones. But a little bit of the endocrinology is coming back. All right. So when is this hormone released? It's released in cases of severe dehydration if your body does not have a lot of water. Because let's think about it. If you're dehydrated, you don't have enough water in your tissues. What your kidney says is, oh, wow, this person does not have a lot of water. Let's hold on to whatever we do have. And let's not just throw it away. Flush it down the toilet in urine. Right? So we want to hold on to as much water as possible. Or if your blood becomes salty for some reason. Let's say you had some French fries. Potato chips. Maybe there's a day where you're just eating things that are a bit saltier than usual. You will secrete this hormone so you reabsorb more water to help balance out how concentrated your blood is. And again, vasopressin is made by neurons in the super optic nucleus of the hypothalamus, and that's then released into the posterior pituitary. The third hormone that's going to act on the collecting duct and DCT is called atrial natriuretic peptide or ANP. So this hormones actually pretty cool because it's produced by your heart muscle, the myocardium around your right and left atrium. And this hormone is secreted in response to high blood pressure. So your heart muscle is sensing how hard it has to work to push blood throughout your entire body. So if your blood pressure is really high, your heart muscle picks up on that and it's going to secrete AMP. And there's four outcomes of this hormone. Big picture. What ANP is going to do is it's going to try to lower your blood pressure. Let's think about this with the kidney. All right. If you want to lower your blood pressure by manipulating the kidney. Would you want to reabsorb or secrete water? Secrete more water because when you secrete more water, your blood volume decreases. Right. Because you're getting rid of that water in your urine when your blood volume decreases. Your blood pressure. Also decreases. So. What is ANP going to do? It's going to dilate your afferent arterial and slightly constrict the efferent one. So it's going to increase your GFR. Remember when GFR is really high. Things are rushed. You're moving, moving, moving, moving. And your urine output is increased because you're just rushing through. So increasing your an output here. ANP is going to inhibit the secretion of renin, which we'll talk about. ANP is going to inhibit aldosterone because aldosterone wants you to retain water and salt. ANP is going to inhibit antidiuretic hormone. And basically we're just going to inhibit the reabsorption of NaCl. And because we're inhibiting sodium reabsorption, we are inhibiting. Which inhibits. Water reabsorption. Right. Because water follows salt. All right, I like that. That makes sense. Okay. So those are the three hormones that act on the collecting duct and the duct. So blood pressure is going to play a huge role in the function of the kidneys. Now we're going to talk about how the kidneys check themselves before they wreck themselves through a process called renal auto regulation. This is going backwards a little bit to GFR. And then we'll call it a day. Once we finish this part. So renal auto regulation is basically the ability of the nephron to adjust their own glomerular capillary blood pressure, adjust their own blood flow going into the glomerulus and to adjust GFR all in house without the use of anything external. This renal auto regulation allows the kidney to maintain a pretty stable GFR, um, even when there are changes in your blood pressure. Let's say you're exercising, you're stressed out about something, and your blood pressure is rising. These mechanisms keep your kidneys stable. That's pretty cool. And so there's two ways that the kidney does this auto regulation. The first is called the myo genic mechanism. The second is called tubular glomerular feedback. And then I'm going to teach you about one final system. So everything's coming together. So this myo genic mechanism, the prefix myo means muscle. And so this mechanism is built on the idea that smooth muscle, when it is stretched significantly smooth muscle, has a tendency to constrict. So you stretch smooth muscle a little too much. It has an automatic system that's going to trigger contraction to help counteract that stretch. So here is how that would work. Let's say you just had a bunch of caffeine, or you're thinking about the unit three exam in two weeks and your blood pressure increases for some reason. Well, then the pressure of blood that's going into your kidneys is higher, right? So that increased blood pressure is going to cause your afferent arterial to feel that pressure. So your afferent arterial is going to stretch a little bit because of your own high blood pressure. And the lower that brightness all too bright for me. Um, so what happens then? Because of that? The arterial after it expanded because of your high blood pressure. The arterial is going to constrict. That's going to prevent too much blood from going into your glomerulus because of your high blood pressure. So that way the glomerular capillary blood pressure stays pretty constant. And then the opposite could happen when your blood pressure falls too low. For some reason, let's say you fainted or I don't know, your blood pressure just went down for some reason. The afferent arterial is going to relax so its diameter will get larger. So that way it allows blood to flow more easily into the glomerulus so your GFR doesn't fall down too catastrophically. Okay. So it's basically a way of saying when your systemic blood pressure changes, when it gets really high or really low, we manipulate the diameter of the afferent arterial to keep GFR constant. And we played around with that earlier. And if you're curious how this works, the afferent arterial is lined with smooth muscle. And when that smooth muscle stretches, there's actually calcium channels on the smooth muscle that are stretch gated. So when the tissue stretches it causes I love that says nonspecific cation channel. It's actually a calcium channel that's going to open that depolarize the, um muscle and then the muscle contracts. So in case you were curious, I will not test you on the details in this picture. But I will test you what's written out as the text in the slide. All right. Now let's talk about renal auto regulation. The tubular glomerular feedback mechanism. So for this, I'm going to go back. All right. So. In a few drawings that I've shown you. Or in a few of these illustrations, they've shown the DCT as being further out away from Bowman's capsule, right? That's not what it actually looks like in the body. Instead, it looks like this. Instead, it looks like this. To where the loop of Henley curves the other way. So the ascending limb is on this side. And so the distal convoluted tubule, when it curves back up into the cortex, it is in direct communication with Bowman's capsule and the arterials. So this is what it really looks like. Okay. Let's go back down to that. Slide where we were at. Okay, here we go. So this is another view of that. Here we have the glomerular capillaries and the zoom in. We have the glomerular capillaries here. We have Bowman's capsule. Surrounding it. And then this little loop right here. This represents the start of the distal convoluted tubule as it comes back up into the cortex. So the DCT is in direct contact with the glomerulus and Bowman's capsule. And so this tubular glomerular feedback is actually pretty funny. It's pretty silly because the glomerulus is receiving feedback about how good of a job it's doing at filtering things out. So the glomerulus is getting feedback on its GFR, if it's too high or if it's too low, because the filtrate that's in the DCT at this point here, it's being monitored. We're looking at that filtrate and saying, okay, is there too much water in there? Is there too much salt in there? What's going on? And so we will adjust GFR based on what is in that filtrate. And so how this is accomplished is through a group of cells called the jug stud glomerular apparatus, or GG apparatus, which is a complex of three cells that's found at the very end of the nephron loop, right where the DCT starts when the DCT starts in the cortex. So the DCT, aka the very last bit of the nephron loop, is going to come in contact with the afferent arterial and the different arterial. There are three special kinds of cells found here. The first type are called the macula dense cells. These cells are the snitches. That's literally all that they do. So the macula denser cells. I put a pink. Can you guys see that? I put a pink little box around. So the macula, denser cells actually form part of the wall of the distal convoluted tubule. And what these cells are doing is they're monitoring the filtrate. They're saying how much salt is in here? How much water is there? How good of a job did the kidney do at filtering this filtrate? All right, so they're the snitches. If something's wrong. Oh, you best believe they're going to tell the police that something was not done accurately. Okay, so the immaculate, denser cells are going to sense any variations in the filtrate composition. Now, let's say for some reason that something's wrong. Okay. And the macula, denser cells are going to tattle on the amaryllis. They are going to stimulate a group of cells called Jocasta glomerular cells or JG cells. We also call them granular cells. And so the granular cells here. Oops. What it really is, is smooth muscle. That surrounds the afferent arterial. So that's what I'm highlighting in blue. Okay. So again granular cells they're also called the G cells. It means the exact same thing. All right. So it's smooth muscle cells around the afferent arterial only. And they will be stimulated by the macula denser cells okay. These granular cells also contain the hormone renin. So they will secrete renin um when that system gets activated. But I'll tell you more about that later. And then another cell type involved are Masango cells. And the Masango cells are actually found in between the glomerular capillaries here. And they can control the diameter of those glomerular capillaries. They can cause the capillaries to dilate or to constrict. Uh, but they don't play as huge of a role as the granular cells do. So they can constrict or relax the glomerular capillaries. To regulate blood flow. So how does this system work? Well, it works in a few different ways. So let's say for some reason that the GFR is too high. When the GFR is too high, your urine is going to have more. What in it? Than normal. It's going to have more. NaCl. More salt and more. What's the other major thing that we like to hold on to? Salt and. Water. So if your GFR is too high, the filtrate is moving through too quickly. We're not giving the kidney enough time to reabsorb that 99.5% of the salt in that 80% of the water. So our urine. We'll have too much water. And salt than normal. So the macula denser cells, they sense that. And they're like that is not right. Okay. So the filtrate is just flying through the tubules. There's going to be more salt and water in urine. Because of that, the macular dense, denser cells, they sense that they're going to stimulate the JG cells with a para xn signal. That's going to tell these granular cells, aka the G cells to contract. Right because the JG cells are smooth muscle. When the JG cells contract, that's going to constrict the afferent arterial. Which is going to help bring GFR down to normal. It could also tell them if Sanjeev sells to contract, which reduces the capillaries themselves, which can also reduce GFR. If GFR is too low. What's the issue with that? It means that the filtrate is moving too slowly. So our urine. Will have little to no. Water. NaCl. Or waste. Right? Because when the GFR was too low, we actually started to reabsorb waste. So the macular denser cells are like there's no waste in here. This GFR is too slow then. So then the macular denser cells are going to relax and calm down, and they are going to relax the afferent arterial. And the Masango cells, which is going to help increase blood flow into the glomerulus and it's going to increase GFR. Back up to normal. So that is how GFR is actually regulated. So we're just building on the system that we talked about at the start. All right. We have our very last system. We're not going to get through all of the slides today, but that's fine. Um, our last system, we're going to go out with a bang. We're going to talk about the renin angiotensin aldosterone system. Super fun. So the Raas this is a hormonal system that's going to regulate salt reabsorption. It's going to involve the granular cells. It's going to involve aldosterone and all these things that we've been talking about. So. Remember I said that those j g cells, those granular cells, they're made out of smooth muscle. They control the diameter of the afferent arterial. They also secrete a hormone that's also an enzyme called renin. So renin is only secreted. When there is a significant drop in how much salt is in your blood. If there is a significant reduction in your ECF volume. So that means if for some reason you've lost a lot of water right in your extracellular fluid. Um, and both of these components reduce NaCl and reduce DCF volume. That's caused by a significant drop in your blood pressure. So basically running is secreted. If there is a drop in your blood pressure or if you lose a lot of blood suddenly. So what renin is going to do is it's going to trigger a system that's going to help you increase. Salt reabsorption by the DCT and the collecting duct. And the benefit what you get out of this renin angiotensin aldosterone system. It's going to help you retain more salt by your body, which is going to help you retain more water. That's going to help restore your plasma and blood volume. Which is going to help raise your blood pressure, because the thing that triggered this whole system was a dramatic lo