talk about uh nephrons, the functional unit of the kidney. Those are nephrons. And you have about a million nephrons in the body. And we're going to see how those nephrons function. And we're going to pay special attention to what's called glomeular structure. This is a specialized vascular structure that's part of the nephron. And it seems really specific that I may be focusing on that, but that's really the the bridge between the cardiovascular system and the renal system. And because it is the bridge, that's where a lot of um mechanisms occur that help control things like blood pressure and blood composition. And of course, that would influence urine composition. So I spend a lot of time talking about this very particular area. There's endocrine functions here. There's um for those of you going into pharmaceuticals, target of drugs is here. It's one of those areas of the body where if you have a problem with the blood, you could control it possibly by f focusing or targeting on this one particular area. So, we're going to start as we normally do with some background information. I'm going to talk about this process called ultrailtration, which I will say a lot in this lecture. And so, as always, I like to make sure we know what that is. Otherwise, it's not a super impactful thing to talk about if you're not really uh comfortable with this term. So, ultrailtration is the process um it's an interesting process. It's the process of producing a fluid and in this case when it comes to the renal system that fluid is going to be called filtrate. So the process of producing a fluid in this case filtrate from blood specifically plasma. So we're going to take the plasma fraction of blood and we're going to run it past this filter and that is the glomemeulus. It's a the glomemeulus is a capillary but it also acts like a filter. And from this plasma, we're going to filter out certain components of the plasma, and that's what could become urine. So urine is really just plasma with some extra metabolites thrown in. So the composition of urine helps give you a lot of information about the composition of plasma. That's why you can do a year analysis and get a good idea of what's going on in the person's body outside of just the basic kidney function. Um, so that's one thing we'll look at today. Um when we think about what items should be allowed to leave the blood again specifically plasma at the glomemeulus this very particular tuft of capillaries via this process. So we're really managing three things here blood plasma the filter that is the glomemeulus and the process that pushes things out of the plasma from the glomemeulus and into the nephron. When we think about what should be allowed to leave here, the pla the plasma going into the filtrate, it's quite a few things. Um, so really we're going to be looking at um the answer and this seems probably very general, but most items most items that are dissolved in plasma can leave the plasma and become filtrate. Most items So the selectivity factor here things that cannot leave it's because they are too big or they have a negative charge. There's an interesting feature to the glomeular capillaries that makes them negatively charged. So they repel things that also have a negative charge. So when we talk about what can leave most items dissolved in plasma can leave. I also like to follow that up with what shouldn't leave. And so again, we should be able to filter this plasma pretty easily based on size of particle and the charge. Once we apply those um sort of filters or those um sort of um structural needs to the filter, we're going to see that there are things that should never So what should never leave the blood and enter the filtrate? That's maybe a little bit easier than what should. So, what should never leave the blood and enter the filtrate? Red blood cells, white blood cells, platelets, and large proteins, large blood proteins like albammen. And the reason why these should never leave the blood and enter the filtrate when it comes to most of these, it's a size issue. Red blood cells and white blood cells are pretty large. Albumin, as far as blood proteins go, it's large and it has a negative charge, so double negative there. It can't leave. And then platelets should be too big. Is it possible to find these items in someone's urine, though? It is. And if you do, it's a pretty good sign of some significant trauma or damage to the glomemeulus, the filter, and that it's sort of its sees, its pores have been blown open. They're too big, and they allow lots of things to pass. One reason that might occur is because of unregulated hypertension. high blood pressure for years smashing up against the walls of this glomemeilus will definitely blow open the holes of your filter such that things can pass through. Other things that could cause the pores to enlarge and let too many things through that shouldn't would be blunt force trauma. Athletes that participate in football or boxing of course could do that. Um so there's different reasons why we might see these items in the blood once they enter the filtrate of the nephron, there's no way to reabsorb them. So once they're there, they're there and they will end up in the urine. It is possible in many cases to heal the glomeulus and stop the loss of these things, but of course a lot of times that's going to require some pretty sophisticated medical intervention to get that happen. Let's talk about pressure within the ovarialis and ultra filtration and how that's actually controlled by an arterial called the eerant arterial. A lot of our physiology, just basic physiology for survival is really based on the ability to get a hold of blood pressure in this area. If you get a hold of blood pressure there, you create the right amount of urine and you manage the right amount of blood pressure for the rest of the body. So, I'm going to put a pen in this and say, I'm going to explain this on my drawing. This is something we can come back to or when you're studying, come back to this and see if you can answer it. But right now, I haven't really talked about enough details to really sort of um make this into a synopsis that's very understandable. But that will change. We're going to go through some details here and see how the nephron works. So, two things on this piece of paper. I'm going to talk about details of the nephron and its components. Remember, the nephron is the functional unit of the kidney. Once you damage a nephron beyond the point of repair, they don't come back. And if you damage too many of them, then you have kidney sort of dysfunction or you lose the function of the kidney. We're going to talk about why they are so incredibly delicate yet important. And then we're going to come over here and we're going to talk about the details of a nephron. And I'm going to pay special attention to this glomeular structure and something called GFR, glomeular filtration rate. And this is a a formula that we can use to figure out how much urine is being produced per unit of time and what that means to the rest of the physiology in the body. So that's our goal. Gonna sort of reset this the first um half of this on the left hand side details of the nephron component. Just sort of some background information. When you did your dissections in lab on Friday, you cut through a whole bunch of nefrons. Like a whole bunch. There's a million nephrons per kidney. Most of them are located in the cortex of the kidney. So think about the very outer rim or sort of rind of the kidney. That's called the cortex. It's only about the thickness of a a a dime or maybe a quarter. It's not very thick but that is where the majority of the nephrons are actually located. All about service area. The outside part of this of the kidney has more service area. So you can actually pack more nephrons in that particular area. So nephrons are the functional unit of the kidney. The functional unit. Again about a million per kidney. And these are again something that's produced during fetal development. And once they're damaged beyond the point of repair, they they don't come back. And that's because they have a lot of different cells and components. You can't really just expect them to heal themselves. There's a lot of different primary tissues involved in this. So we want to take care of the kidneys so that we can take care of the cardiovascular system. For example, such an integrated set of systems. Usually when you talk cardiovascular system in a way you're talking renal system. So as I mentioned each nephron since it's the functional unit of the kidney talk about what it does. Each nephron it's going to do a couple things all very important for homeostasis. First, as I kind of alluded to already, each nephron creates a fluid and that fluid is called filtrate and that comes directly from plasma. That's a really important job. In the beginning, when filtrate is produced, it has the same osmolality as plasma. At at the beginning, it's an identical fluid. And then the job of the nephron is to change that via osmo regulation. Take some of the components out, put some more components in. We'll see that the nephron is just this constant give and take, give and take, give and take between blood and filtrate until the nephron thinks it's balanced it just right. The blood then leaves, goes back into the renal vein, which dumps into the inferior vennea, and the filtrate becomes urine. But you get more than one shot. That's the nice part about this. It's not just a you got to get it right the first time or you're, you know, forever stuck with it. There's a lot of give and take between the blood and the filtrate, but when it's first created, and that's very important to make sure you understand, which I will diagram here in a minute, but when it's first created, plasma and filtrate have the same osmolality. Same osmolality. Another thing that the nephron does is obviously helps the body excrete waste products. What are some waste products that we might want to get rid of that we don't want to reabsorb? What could be pushed from the plasma into the filtrate and the kidneys are like, "Oh, get rid of that. Do not reclaim that. Do not put that back in the blood." What do you think? Excess of water can be reabsorbed, but if we have excess, it might end up in the urine. But what are some compounds that the body's like, "No, make sure that does not come back. All right. Well, we'll think about that. We'll think about that. It's a give and take. Some things can be reabsorbed and some things No. And we'll see that we're going to maintain a salt and water balance. And we think about maintaining salt and water balance. This really is the principle of blood pressure maintenance. Blood pressure maintenance. That's why we are so concerned with salt and water balance. Other ions are definitely going to be part of osmo regulation. But sodium and chloride play a huge role. The reason for that is if you get a hold of your salt levels, sodium chloride, then you can get a hold of your hydration levels because water follows sodium. And so if you want to move water into one area of the body or get rid of water in one area of the body, you're going to have to move sodium, chloride usually follows. So we just say salt. But sodium is really the driver there. And then as I mentioned, we're going to coordinate blood pressure regulation. The nephrons have the ability if blood pressure is too high, the nephrons will help rid the body of some of that water and that reduces blood pressure. There are pharmaceuticals you can give people that increase that. They're usually called diuretics, specifically loop diuretics. Loop diuretics are an old class of compounds. They target a very particular part of the nephron and they prevent that part of the nephron from reabsorbing water. They say, "No, we're not going to reabsorb that water." This compound does. It's lost in the urine. And that's the whole point of a diuretic. You want to pull water from the body. Maybe the person has some fluid accumulation and you need to get rid of that so the other cells can get what they need. You don't want edema to accumulate. So, diuretics, loop diuretics, help with that by honestly controlling sodium because water follows sodium. You move sodium in just the right way and water usually is very comp. follows. So, it's an interesting relationship. Even in your higher level physiology courses, you're still looking at diffusion. And that's a kind of a hard thing to get around your head because you're like, "Well, diffusion. I've had that since third grade." But it's still just that important. It's still about diffusion, getting a hold of who is moving what and when. We will also see that the kidneys play a big role in balancing acids and bases in the blood. So the kidneys play a big role in blood pH maintenance. What should blood pH be? Let me arrange. Healthy blood pH. Let's see here. Let me write this down first. I think I heard the right. We would expect 7.35 to 7.45. That's the homeostatic range. 7.35 7.45. Not exactly neutral. A pH of seven would kill us. So, we don't want that, but not too acidic. Sort of the Goldilocks principles. Not too much, not too little, just right. So, the renal system, the kidneys, are really good at helping with this, but they're slow. We have another organ system, I almost gave it away, that does it much more quickly. What is that? What is the principal organ for balancing blood pH quickly? Take a deep breath in and ponder that. The lungs. The lungs because if you can excrete carbon dioxide, then you can control pH levels quickly. The kidneys will help, but they're slow. So, the kidneys are really good at what they do, but they're not fast. So, if you're working with a patient that has some sort of disruption to blood composition, the kidneys may help them solve that. It may help you resolve the issue, but you're going to have to probably figure out a way to resolve it faster than the kidneys are going to have it happen because the kidneys filter blood and that's fairly slow process. So, pH management though, they do contribute. They can manage hydrogen and hydroxide levels and that's really the foundation of of blood pH. All right. As saw in lecture or lab, excuse me, last week, um the kidneys receive a lot of blood and we saw the hilum, the indented area on the medial aspect of the kidneys. And in that indented area, that's where we see urtors exit. We saw renal artery enter, renal vein exit. For those of you in my lab sections, I think we found arteries and urtors. The veins are a little tricky. Some people did find the veins. So, good job there. Um, but there's a lot of blood going into and out of the kidney. So, collectively the kidneys, so talking about two here, collectively they receive 20% 20 to 25% of total cardiac output. This is at rest. This would change if you're exercising, but just at rest, the kidneys are going to get 20 maybe 25% of total cardiac output. That's a lot. Total cardiac output. How many liters of blood in the average adult? Five. Five liters is a pretty good pretty good average. A little bit more in in larger people, but about five liters. So 20% of five liters is what's going to the kidney every minute. They are well perfused with blood. That's an understatement. I always thought it was strange they didn't get total protection from the skeletal system. You have a soft organ and a lot of you commented on how squishy they are, right? The squishy factor was very high in the kidneys. Um, they don't have protection from the body wall. They're considered to be retroparitinal. So, automatically not the same protection as parts of the GI system. And they only get about the top third, superior third of the kidney in humans is protected by the ribs. the rest of them are just sort of vulnerable. I always thought that was kind of um an odd feature for many mammals to have a organ that's not protected by the body wall that gets that much blood that doesn't get skeletal protection because their risk for hemorrhaging from trauma is certainly there and that's just how most mammals are designed though. Um but it is strange. So they get 20% of total cardiac output. So this is a liter per minute thing and they filter 180 lers of fluid from plasma every day. They make the kidneys collectively make 180 lers of filtrate. That's a lot. 180 lers. I don't know how many gallons that is, but it would be a lot. You don't lose that much fluid, right? You don't have that much fluid in the body. you only have about five liters, maybe six liters depending on your size. So that tells us the kidneys reabsorb a lot of what they push out. So their goal is to just push push push and then sort through all the stuff and then reclaim what they want. And so that's how they do it. In a healthy person, it works really well because you end up with um not much urine. So I'm going talk about how this works here. So my first question for you, kidneys collectively filtering 180 lers of plasma creating 180 L of filtrate per day questions you know discussion type question. How much urine is produced per day after filtering that? This is just a a guesstimate. I have not talked about this. So it's a wild guess is totally fine. You think the average mc duration or process of urinating? How much urine does an average person produce? 10 liters. 10 liters would be a lot. That' be a lot. It's not much. And again, this is the average healthy person only produce about a liter and a half a day. That's it. So, how good are the kidneys at reabsorbing all the water they push out? Well, in a healthy person, they're really great at that. If you have a lot of ADH secretion, like being secreted from the posterior pituitary, what happened to that amount? You have a lot of ADH in general circulation. How much do you produce? You expect this number to go up or down? we would down. So if the person's severely dehydrated, they would create much less. Much less. If they were overhydrated, they would create much more. Overhydration is not typically a problem. Usually, most people are chronically dehydrated, but every once in a while, you can encounter a person that is overhydrated. Uh they would have incredibly high blood pressure, usually somewhat of a dull headache. They can be confused. And it actually kind of looks like if a person's dehydrated, the symptoms can be the same. But you can get a pretty good indication by pulse pressure about how much blood volume they have on board. So um if you do uh mucal um mucal capillary refill time, you would know pretty quick if they have a lot of water on board or not. So when we talk about how the kidneys are going to do all of this, how are they going to do all this? So hopefully I've kind of set the stage for the fact that kidneys are kind of a big deal. This is what I want to talk about really for the rest of the lecture. How can nephrons, the functional unit of the kidney, selectively decide what are they going to keep and put back into the blood and what needs to be excreted. So obviously they produce a lot of filtrate at first. Filtrate has the same osmolality as plasma. and they're going to take back the vast majority of what gets pushed out. But some of it some of it's got to go. So they're sort of really smart for being just made of a collection of cells. Very very smart. So I'll be discussing this process in a healthy adult. This will be a discussion that does not have anything to do with diseases or trauma because that would change this a lot. So the endocrine system can change this for example quite a bit. As I mentioned before, pharmaceuticals can change this quite a bit as can past trauma. Um so that's a that's a whole another lecture, but we're going to keep it just really focused in on the average healthy adult. We're going to see there are three main processes at work in order to get all of this to happen just right. three main processes and I'm going to be defining these. These um are you know every concept that I talk about has weak points on the exam. These are the weak points on this exam. Not really understanding what these are u beyond a definition. I think most people are pretty good definitions but being able to apply it and figure out what happened that's where people get into trouble. So I wanted to be very clear about what these things are, what they mean, what they do, and what would happen if one of them doesn't work correctly. What would happen to urine volume or urine composition? And then, of course, blood volume and blood composition because those two are really tied together. So, processes that are always at work in the nephrons. And as I draw this out, I will be mentioning a couple of photos that influence this. So we are still sort of under the broad heading of endocrine system right now which is why I'd like to remind you this is very tightly controlled because as I've mentioned we've already talked about blood pH blood volume maintenance those are two important regulated physiological variables. So let's start with the process of ultrailtration. As I mentioned before this is a um a pushing pressure is what we'll see here in a moment. A pushing pressure creates filtrate and that pushing pressure is going to be blood pressure. We have pretty high blood pressure in the glomemeulus, much higher than we would see for sure in really any other capillary bed in the body. So we're going to see this high blood pressure in the glomemeulus. It's actually a good thing. We're going to push out some things across the bulus and that's filtrate and that is ultrailtration. Reabsorption and secretion. These are the two that usually get people more than ultrailtration. Reabsorption. A good way to think of that is we are reclaiming specific items from the filtrate. Very specific items in very specific amounts. And that can change. This changes all the time based on the status of the blood, the composition. Just because you're reabsorbing this amount of magnesium now does not mean you'll reabsorb that much magnesium tomorrow. It's based on diet which changes blood composition which has to be sort of parsed out by the nephrons. Secretion, this is where I don't have a good way of like connecting these words. it works here. But secretion, we will see items from blood um are for lack of a better term put back into the nephron, put back into the filtrative nephron. You have multiple options in the nephron to accomplish reabsorption and secretion. You only get one chance for ultra filtration because you only have one glary per nephron and that's where ultra filtration happens. When it comes to reclaming items or you need a second chance, need a second pass to get rid of some of those other metabolites. You have multiple chances to do this. But reabsorption is always taking things from the filtrate and putting it back into the blood. And secretion is always taking things from the blood and putting it back into the filtrate. That doesn't mean it couldn't be reabsorbed later. It's just that these two are defining directional movements going into the blood going back into the filtrate. It doesn't mean anything more than that. You can't read more into it than that. And then of course influenced by hormones like ADH or aldoststerone. Aldoststerone is a really interesting hormone that helps us um increase the reabsorption of sodium. Um, so there's a lot of different hormones that impact the nephron again because of its relationship to blood. So this is kind of some background type stuff about the nephron. I'm going to diagram and a particular type of nephron on the right hand side. But are there any questions about sort of the basics of a nephron? Nephron function nephron. Yeah, you briefly mentioned this and you might go over it later, but did you say there was one per one nephron? Yes, it's a good question and I will diagram this out but there every nephron has its own glomeialis other questions. All right. Well, we're going to start with um looking at the structure of a very particular nephron. And this nephron is called a jaxa medularary nephron. It's what you see in textbooks. It's what you've seen before. I used it in lab because this particular type of nephron is really great at reabsorbing water. But there's a catch. There's always a catch. Only 155 15% of your nephrons look like this. The vast majority of the nephrons in the human body don't look like this. So once again, we've been lied to. So I'm going to present this because it has the most physiological features. And then I will contrast that with what most nephrons look like. Most nephrons. So, it's an interesting study in evolution. Mammals that live in very dry climates like the kangaroo rat, the humble kangaroo rat, they have more of these types of nefrons, these dutyary nephrons. Mammals that live in a freshwater environment, like the humble muskrat, those are pretty active right now. They would have less of these. So, the kidneys are a reflection of our life history on a terrestrial biome, which is really cool. They're pretty adaptable, too. Desert mammals can change their nephron structure within one generation, which is an amazingly short amount of time. So, it's an interesting study again in evolution and where you lived and how much free water was available. But humans have um kind of an average run-of-the-mill type of nefrons which tell us we didn't have an abundance of free water when we evolved, but we had access to some. So, we're going to look at just again this is a basic line diagram as you can imagine. I'm going to add to this and I'm showing you I'm going to give you the name first. Jimeary nephron. Jax medularary nephron. Only about 15% of our nephrons look like this. So in other words about 85 that's an eight about 85% of nephrons they look very different they're called cortical nephrons they only exist in the cortex of the kidney the cortex of the kidney is not very thick so they cannot look like this so there's your title I couldn't fit it above so it's below um we're going to be talking about sort of a line diagram. We're going to be going over the components of the nefron. Um, and I'm going to be adding to this. So, I'm going to just give you a minute to work on this. Um, everything here is part of a nefron. I will be adding in little bits of blood supply and I'll be talking about collecting ducks and I'll be sort of overlaying this with what we saw for a dissection on Friday. So, you cut through a whole bunch of these. You just didn't know it. You cut through a lot of cortical nephrons as well, but it's all soft tissue, so there's no way to know. All right, I'm gonna Just start by labeling some things that you've drawn. And again, everything here is so microscopic. The walls of the nephron here are just one cell thick. And they're going to be really in direct contact as much as possible with some specialized capillaries. So the first um structure that you have here sort of this half moon shaped. This is called the Bowman's capsule and it leads so Bowman's capsule it leads to um a part of the nefron here called the proximal convoluted tubule. Proximal because it's nearest the Bowman's capsule. The Bowman's capsule will contain the glomeilus. You can see how it looks like a funnel or cup. It will contain the specialized capillary called the glomeilus. Everything in a nephron is named for its proximity to this area here. So this tubule is closest to the glomeulus. So thus the word proxal convoluted because in reality uh this thing would look like a telephone cord. I really miss the old phone cords and that everybody had a phone cord because everybody what that meant. You know, some people only have cell phones. They're like, "What are you doing?" Like, I just like to make gestures in the air. So, but convoluted because this would be very very twisted and that increases surface area. And then, of course, tubule because it is a small tube. This is usually abbreviated PCT. Just a lot easier to write PCT, but I think it's good to know why it's made. The next part of this, this giant loop goes down and it goes back up. This is unique to a jaxamemedary nephron. If this was a cortical nephron, it would just make a little dip and go right to our tuble and it would be a pretty short story and it wouldn't be too interesting. But in the juximilary nephron, we have this really long extensive feature called the loop of henley. And the loop of henley has one job and that's to reabsorb water. This is the reason we can exist on lands. I know people are like it's for skin, it's for legs. It's not the lube of Henley. This is what's allowing you to live on land and not instantly be dehydrated by the dry air that's around us all the time. So the lube of Henley, this whole thing, I'm going to put like a dotted line here that sort of illustrates where it begins. And I'll do the same thing over here. Where does it end? So everything between these dotted lines is the loop of Henley. So I will write that down here. Loop of Henley. Everything's named after people's names. The loop of Henley, as you can see, it's it's one continuous tubule, but we talk about it as though it's two distinct parts almost like it's not connected. Anatomically, it's definitely connected, but it has two very different features, and that's based on the flow of filtrate. The first part of the loop of Henley is called the descending limb. Usually and properly it's the descending limb of the loop of Henley. But that's kind of cumbersome. So I already wrote loop of Henley. So this is the descending limb and that's going to refer to the flow of filtrate. Over here we have the ascending limb. ascending limb of the loop of Henley. And again, this is just describing the flow of filtrate. So filtrate is going to go down. It's going to make 180° turn and it's going to go back up. So anatomically, it's one two filtrate flow dictates what we call it. Physiologically, these two limbs could not be more different. Could not be more different. This is going to be really great at reabsorbing water. highly permeable to water, not permeable to anything else. This is impermeable to water, but highly permeable to sodium. And that's going to set up a concentration gradient. It's going to be really great for pulling water out and putting it back into the blood. So again, one tube, two functions with some strange names thrown in. Moving to our last portion of a nephron. Everything else from here is shared with additional nephrons, but I kind of put a dotted line in. Again, this is about where your ascending limb ends. And we're going to be in what's called the distal convoluted tubule or DCT, distal convoluted tubule. And you probably can guess why it's called that, distal, because it's farthest from the Bowman's capsule and glomeulus. So distal convoluted because once again we have a very sort of twisted spiralally type tubule all about surface area and then of course it's a tubule. Our last portion that I have here this is the collecting duct and this is shared by many nephrons. So it's not technically part of a specific nephron. It's a collectively shared draining duct. So I'm going to just label this here. Um the collecting duct would have formed. It's a U. Let me try again. It just does not want to participate. This is a collecting duct. This is when you um cut through the renal pyramids on Friday. We were looking at those. And if you caught them in the light just right, they looked like they were fenistrated or had rays. You noticed that. That's a collection of collecting ducts that actually are bundled together. Even though they're microscopic, if you put enough of them together, you can sort of see their outline if the light's just right. So, that's kind of where they would lead. The collecting duct would lead all the way down to uh the renal pill, which drains into a minor calix and then a major cal. So, just connecting some of these back to things you saw last Friday. Again, we're at the microscopic level, so it's kind of hard to get your head around it, but you did see sort of the results of these All right. So that's the overview of a jaxameularary nephron. Again, only about 15% of our nephrons look like this. If this was a cortical nephron, you would not see this long loop of henley. You'd see just a little divot that connects this tubule to that tubule. Um, but hopefully you can understand or appreciate why talking about the jamemedary nephron is much more sort of um helpful for you in your future. If you understand this, then you'll understand a cortical nephron much more easily because it's much simpler. Is it still a loop of a cortical nephron? It depends on the textbook that you're consulting. Some textbooks show no loop of henley and some probably are just a straight branch. Some call it a truncated loop of henley. Some just call it a loop of henley. So, it's all over the place. It's a good question. So, just depends on what the author, I guess, decided to call it. I'm going to go back and add some physiological features to this and that's going to require blood vessels. So, we're going to take a step back from the tubule and talk about blood flow. Any questions on this before I do that? Any questions? Be adding a lot of stuff to the area nearest the Bowman's capsule. There's a lot of physiology that happens here. And honestly, we're just kind of starting to understand this area to the point where we can design some pretty sophisticated pharmaceuticals that get a hold of all sorts of physiological problems. It's it's kind of been an I don't want to say an underresarched area, but it it hasn't easily given up its secret. So, it's an interesting um sort of field to get into. I'm going to introduce to you um a portal system. And we saw a portal system when we looked at the hypothalamic hypothesal portal system. remember that in the brain. This is the second of three portal systems in the body. The third would be the hippatic portal system which carries blood from the small intestine to the liver for processing. So there's only three portal systems in the body. In the hypothalamus and pituitary, the kidneys and then the hippatic or liver portal system. Um, wherever you find them though, they share some similar features, which is you're going to have two capillary beds separated by a specialized set of of technically veins. Um, so some interesting things about this particular area. Our um renal portal system or um the glomemeulus is what we're going to be looking at starts with what's called an aerant arterial and that's what I'm going to draw here. This is our aerant. We've seen the word aerant before aerant arterial and we know that aerant whether we're talking about action potentials or flow of blood usually means we are advancing towards a point of reference. Aerant action potentials advance towards the central nervous system. Aerant blood flow advances towards our point of reference which is again the glomemeulus and the bowman's capsule. So the aerant arterial this would have blood in it coming from the renal artery. So it would be highly oxygenated. It would contain nutrients but it would also contain waste products and metabolites that need to be filtered. So the composition here is a little different than what would be leaving the nephron after all this osmo regulation takes place. So the aerant arterial has pretty thick walls. There's um a good amount of smooth muscle here and it has a pretty wide lumen. It is really designed to facilitate a lot of blood flow but it's also designed such that that blood flow could be constricted and slowed. So we see a high volume area that can also be controlled. So it's a very interesting area. Apher arterial apher arterial leads directly into the glomemeulus the specialized tuft of capillaries. I'm going to draw this. You do not have to follow the same pattern that I do. Uh it's just a twisted tuft of capillaries. So don't you know don't get too far into the weeds here about how I draw it. I am going to draw it rather simply to give myself some room to describe what happens here. But the glomemeulus is a twisted tuft of capillaries that has a lot of physiological implications. And again, I'm drawing it rather simply. We're going to see this twisted tuft of capillaries. Its goal is to provide a lot of surface area so that we can actually get the process of ultrailtration to happen relatively efficiently. So, our aerant arterial is going to lead to the glomearulus. So no matter how you draw that, you cannot draw it incorrectly. So that's the good news. You cannot draw this incorrectly. I'm going to label it down here. So there's the glomeilus and then draining the glomemeilus is another interesting blood vessel. This is called the eerant arterial eerants just like eerant action potentials led away from the central nervous system eerant blood flow leads away from this particular point of reference which again is the glomeulus. So I will label this up here eerants because we are moving away. Couple things about the eerant arterial just like I mentioned about the aerant arterial the eerant arterial really it's big difference on purpose how it differs from the aerin arterial is that the eerant arterial has a um compared to the other one it has a naturally um thin or decreased lumen size It also has smooth muscle in its walls. So we can make that even smaller. But compared to the aerant arterial, the eerant arterial has a naturally smaller orally. And I will remind you it still has smooth muscle. So before we go any further, let's talk about why are we so concerned about the luminal size of these arterials? Like that seems like a really specific detail, but it turns out which one you constrict and which one you open will control blood flow through the glarius. You kind of have like an on switch and an off switch. So let's test this out. If we wanted to increase blood flow and pressure in the glomemeulus because we needed to increase the amount of filtrate ultrailtration happened right here. If we need to increase the amount of filtrate produced we do one of two things. We would close this and we relax that. What you do is you're pushing more blood to the glomearial and you will inevitably increase blood pressure in the glomeulus and make more filtrate. The opposite would be true. you really didn't want to produce much filtrate. Maybe you're dehydrated and you don't want to lose any water any more than you have to. In that case, you can constrict this and open that because you want to decrease blood pressure here and then you'd have less pushing pressure. You'd produce less filtrate and that would help conserve water. So having smooth muscle cells in the walls here that can work at different rates or independently really allows you to kind of think of it as like a gas pedal brake pedal for increasing or decreasing blood pressure within the glomeulus. The eerant arterial will wrap around and create another set of capillaries. So, as I mentioned, this is a portal system, and it wouldn't be a portal system if we didn't have another capillary bed. So, I'm going to extend this and just introduce what are called the paratubular capillaries. I'm going to come back to the glomemeulus pretty quickly, but just for the sake of being thorough right now, I don't really have a portal system up here because I've only drawn one capillary bed. So, I'm going to at least finish that particular thought before I come back to the glomeilus. So the eerant arterial leaves the glomemeular area otherwise called the renal corpusle. I'm just going to condense this into one vessel here to make it easier to draw and it just absolutely wraps around this proximal convoluted tubule and then it goes in several different directions after this. But these seemingly simple red lines here are part of what's called the paratubular capillaries. So they too are a capillary bed. And once we have that sort of detail down, then we do have the basics of a portal system. Two capillary vents separated by a special set of vessels. In this case, But the blood flow is continuous from the glarus to the what I want to focus on is making again this is where a lot of physiology happens that helps maintain homeostasis in the body. For those of you going to professional school you're going to spend weeks here. So I at least want to give you like a background of what this is so you have some idea of why it's so important. Any questions before I continue talk about the process of ultrailtration and the creation of filtrate? Ultrailtration and the creation of filtrate happened right here. This is the only place that can happen. Okay, I'm going to zoom in pretty close on this area. We're going to be looking at blood flow coming up to the glomemeulus. We're going to see the process of ultrailtration is going to create what's called primary filtrate. Primary filtrate is the first filtrate produced has the same osmolality as blood. So it's not balanced. It's just been created. I'm going to see how far I can zoom in on this. And again, this is going to be a normal healthy person with no problems with hydration. Just an average person. So this aerant arterial is bringing blood at a pretty good pressure a pretty good rate and the glomemeulus has a blood pressure of about 55 millimeters of mercury. Like I said it's really high for a capillary. Most capillaries are between depending on which arterial side or venial side but just for simplicity sake most capillaries have a blood pressure of about 10 maybe 12 millimeters of mercury. So this is exceptionally high which tells us it's got a job on purpose and that is to push stuff out and create filter. So that's a high blood pressure for a capillary bed. When we bring blood to the glomemeulus, we will see certain things are pushed out. But we also have other blood vessels that we have to peruse. So you can't push everything out of the glomemeulus or your your pressure for the rest of this vessel system would fall too low to be viable. So we're going to push some things out but not all. So I just like to remind people we talk a lot about pushing things out and I think it can make it seem like we lose all the blood here but we certainly don't. So at the glomemeilus we're going to see the process of ultrailtration happen. And I'm just going to write you for that ultrailtration. And as a result of ultrailtration we get what's called primary filtrate. So first degree for primary primary filtrate that's what we produce. Same osmolality as plasma. If plasma is 300 millol this will be 300 mill. If plasma was 275 would be 275. All we're doing is creating it. Because the osmolality is the same, that tells us we have a lot of blood that we still have to deal with and it will be drained by the eerant arterial which right now still has the same osmolality as the filtrate. Then this all we've done is push some stuff out. So primary filtrate is not the same as urine at all. The composition between primary filtrate and urine is going to change a lot. But whatever we do push out, excuse me, through this process of ultrailtration will collect in the Bowman's capsule. So the Bowman's capsule collects fluid that we call primary filtrate. The Bowman's capsule, excuse me, I'm losing my voice. Um, the Bowman's capsule doesn't alter the composition of that filtrate at all. All it does is catch it like a funnel and send it to the next portion of the neop. So, Say that again real carefully. A Bowman's capsule does not, cannot, no way, no how, never will alter the composition of filtrate. It doesn't have that ability. It's actually made of some um epithelial cells here that are completely inable. So, it makes a great catch or a filter, but that's it. Once this filtrate though enters the proximal convoluted tubule, its composition starts to change dramatically. absolutely dramatically such that by the time the filtrate leaves a proximal compliment and enters the first part of this it is almost unrecognizable in composition. It's still a fluid of course. Questions on making filtrate and move into proximal convoluted tubule on our tour of the nephron. So whatever we produce here flows into our proximal convoluted tubule. A lot of change happens here. I'm going to hit the highlights in the interest of time. I'm going to talk about how this filtrate changes dramatically in the proximal convoluted tubule. So as our filtrate is pushed through here, the cells of the proximal convol tubule. So the cells that make up the wall here, they're very very complex cells. They have a lot of transporters and ion channels and pumps. They can do a lot. But a few things we could say for sure is that as the filtrate flows through here in a healthy person, 100% of glucose should be reabsorbed. I'm going to talk about things that should be reabsorbed, meaning put back into the blood. 100% of glucose. Whatever comes out here and flows into this, you should have cells here that can easily facilitate the reclamation or reclaiming of glucose and it should go right back into the blood. Remember, we should never have glucose in the blood. If person does have glucose in the blood from a cell standpoint, what's happening pathophysiology standpoint is if a person has glucose in the urine, excuse me, they have glucose in the urine, it's because the cells here are so overwhelmed trying to move the glucose out and back into the blood that they miss some. And once your filtrate comes into the loop of Henley and all the way out, there are no other chances to reabsorb glucose. Our only option for reabsorbing glucose from the filtrate and putting it back into the blood is here. So this is what happens when people have for example type two diabetes. It isn't regulated. Their blood glucose levels are high. They have too much um glucose in the filtrate and you do not have the ability to reclaim all that from the cells here. So inevitably it ends up in the urine. So 100% of glucose is reabsorbed here put back into the blood. Other things we see reabsorbed here, most amino [Music] acids, most amino acids, if you're going to reabsorb amino acids, they too get pushed out. If you're going to reabsorb them, it's going to be here. Some amino acids do not get reabsorbed. Some of them don't get reabsorbed because you produce them in the body. And if you eat them, you'll have too much and they end up in the urine. Asparagene is an example of that. This is why you have stinky pee. If you eat asparagus, it's because you've got too much asparagene already. You get a lot of asparagene in asparagus and it ends up in the urine. So for you vegetable fans out there, that's what's going on. Um, other things that can be reabsorbed in the proximal convoluted tubule include some water and some ions. Let me write water more clearly. Water and ions. How much amino acids? How much water? How many and what type of ions though? This is all conditional on the composition of the blood. The only thing we can say for sure is that 100% of glucose should be. The rest really depends on the what the person ate and the composition of the blood. We can also see secretion happening here as well. We can have things go from the blood and go back into the proximal convoluted tubule. This is not unusual. We can see secretion of things like water. Maybe we reabsorb too much ions, ura, ura protein metabolism byproducts. So it's a give and take. As I mentioned, just because you push it out doesn't mean it's that way forever. you have a chance to reclaim those things and maybe secrete some extra things. So by the time our filtrate enters the loop of Henley, it just looks so different than in composition than it did when it was first produced. So let's talk take a look at what happens as our filtrate moves down the loop of Henley. Any questions so far, including handwriting, which It's been unusually bad for me. Yes. Okay. So, I don't know maybe this is always interest, but how does how do the molecules know when to diffuse um like that are in the blood? How come they don't diffuse like before that proximal comple? So, the glomeulus has allows a lot of stuff to be pushed out molecules once it enters the capsule. So get a choice. No secretion happens here. Once it hits the primary or the proximal tubial cells here are very specialized. Some have glucose transporters, some have amino acid transporters, some have ion transporters, but the cells here will sort of sort through that. Does that make sense? your question. Other questions before I continue talking about the loop of enlightening? Okay, we're going to see that the filtrate is going to change dramatically as it goes down this loop of Henley. Let me give you a couple numbers. Osmolality is something that we talk a lot about. In the blood, we're going to go with 300 millos mole. Primary filtrate. I'm going to write this in a different color just so you can see it. Primary filtrate 300 millosmo. Even the filtrate that's about to leave the PCT, it's still 300 millosmo. We changed the composition, but we didn't change the concentration. We may have more ura, more hydrogen here, but we reabsorbed a constant amount. So, we're still pretty much balanced. I'm going to give you another number, though. This is very dramatic and helps really illustrate what this first limb does. By the time we get down to here at the bottom of Lubam Henley, our milliosmold is about 1,200. That's dramatic, isn't it? We went from 300, which is kind of in our consistent number, down to,200. What must have happened to get that number to occur? Remember, we were at 300 here and now we're 1200. What must have happened? You got two options. you get rid of water and that is what happens here. You could have added a lot of things if this was just a hypothetical like two solutions in a beaker kind of thing. You could add salt but in this case what are we doing? We're getting rid of water. That is the entire purpose of this limb of the loop of Henley is that we are going to suck out as much water as possible and down here we're just really left with a salty sludge. There are of course other compounds here but salt is the main contributor to this osmolality change. So as our filtrate leaves the proximal convoluted tubule comes down the descending limb of the lubam henley. The cells here that comprise the walls of the lub of Henley, they are absolutely chocked full of aquaporons. AQP. Aquaporons are the key to getting water out. We lose an awful lot of water from the filtrate here. Where do you think that water goes? Back into the pair tubular capillary wrap back around. That's how truly that's how we're doing it. But water doesn't move on its own. We have to convince it. What does water follow? Can you remind me? It's sodium. I'm just going to like collectively make it salt. We have to convince this water to leave. Just because we have aquaporons, water channels, doesn't mean water will leave. We have to motivate it. What's motivating it? Sodium. But again, I'm going to combine it with salt. So the next question is where is that salt coming from? Before you answer that, I'm going to give you another number. This is like math and physiology on the last day of lecture. Who doesn't love that? When we come back up here to the distal convoluted tubule, the osmolality is 100 millosol. We went from 1,200 back to 100. What must we have done to that filtrate to make those numbers happen? We lost salt. You got two options to change these numbers like this from 1200 to 100. You got two options. You can either pull out salt and that indeed is what happens here. If this was just a beaker example, you could also add water. But that's not what we're doing here. We just like to be clear about how we could change these numbers. Both of these are options. But in Henley, we're going to see that the ascending limb is impermeable to water. It won't deal with water at all, but it's really permeable to salt. And not just permeable to salt. It has pumps that move sodium. It's like just get out. I just cannot tolerate sodium right now. So it turns out as this filtrate comes back around, comes back up the ascending limb of the loop of Henley, the cells that make up the walls here are absolutely permeable to sodium and then again chloride follows. So you end up with a bunch of salt in your extracellular fluid and that's what these red dots are. All sorts of ways to get this salt out. Passive diffusion, active transport, you name it. The ascending limb of a lube of Henley is just all about getting that salt out. And as molecules tend to do, they wander around. They impact the extracellular fluid environment in other areas like the descending limb. And if we have a lot of salt here and we introduce a filtrate that's got a lot of water and we have aquaporons, you've got all you need to pull water out. You've got a method which is or a way which is aquaporons and now you've got motivation which is salt. So the loop of even though it's one tubule it works so differently. salt leaves pulls water out both go back into the blood. So, it's a really great way to conserve water. They believe this again is what really allows us and most mammals to survive on pretty aid, dry terrestrial environments. This is how we conserve most of our water. It's an amazing system with a lot of cool evolutionary history. I'm going to move into the last part of our nephron. The last part of our nephron, the distal convoluted tubule. At this point, we've done a lot to the filtrate. We created it. We reabsorbed some stuff, secreted some stuff, we reabsorbed some stuff, absorbed some stuff. We have spent a lot of time carefully balancing osmo regulating the filtrate. By the time it gets to the distal convo tubule, we don't want to change it that much because we changed it drastically in the DCT. You're basically negating everything you just did. So, we don't want to mess with it too much, but we would like to have a little bit of opportunity, just one more chance to finally manipulate the composition of that filtrate. And that's really what the DCT is for. we see sort of what I call final chance, the last chance for reabsorption or secretion. You're not going to change a lot though. Final chance for reabsorption or secretion. We may reabsorb or secrete some ions. That's about it. Little bit of water, but not much because this is our final chance. Last call. balancing. This is a great place for pharmaceuticals to target because if you change the composition of filtrate here, the nephron has no chance to change it back. You're basically like manipulating it. Like I will change your filtrate and you can't get a say back. And that's really helpful for drugs that target things like high blood pressure for example, they usually old classes of drugs works here because if you pull water out and put it into the urine, then you don't get a chance to read it. So that's kind of nice. By the time filtrate leaves our distal convoluted tubule, it's going to enter the collecting duct and at that point it's mostly urine. Mostly urine. The only time that could change is if ADH is present. So if ADH is present, your ADH receptors are actually here. ADH receptors ADH receptors actually exist on the cells that comprise the collecting duct. This is really the only chance, only way you're going to change that filtrate at that point. So if we have ADH that's been secreted from the posterior pituitary and if it binds these receptors here, it will allow water to leave. That's what ADH does. It causes whatever water may still be in that filtrate. It causes a portion of it to be pulled out, reabsorbed, put back in the blood, so you don't lose so much of it. And that concludes our tour of the Nefron and of our lecture class. Of course, you still have lab tomorrow. Please make sure you wear appropriate footwear since we're doing dissections. You have any questions, let me know. Otherwise, I'll see some of you tomorrow. Have a good afternoon.