Kidney Filtration and Reabsorption Overview

Don't memorize these numbers. This is just kind of showing you that, yes, we produce about 180 liters of filter today. We reabsorb 99% of it and excrete upwards of two liters. We reabsorb about 99.5% of all the sodium that's in that filtrate. Glucose. Yeah. We do actually get glucose in our filtrate, but in a healthy individual, that glucose should all be reabsorbed and you should not have glucose in your urine. We'll talk about that transport process shortly. And then urea is one of the major waste products that we're trying to get rid of through this process. Notice that some is actually reabsorbed and that's okay. that does kind of help manage some pH. It also does play a role in maintaining an osmotic gradient in the medulla as well, but we do excrete about 30 grams of that per day. We absorb about 44 percent, but anyway don't memorize those numbers they're just kind of for reference. Now if we're producing 180 liters a day, and I don't think this was on the video, This is more section 13. Still that same. Yeah, I think this is still section three. But we have to obviously reabsorb that. I want to make sure you understand that there's two kinds of reabsorption specifically for water. And we're really only going to focus on water and sodium and look at. those mechanisms for getting those back in, and glucose. That's really what we're going to look at. So there's two kinds of water reabsorption. There's what we call obligatory and facultative. Obligatory water loss is water that is always going to be... or sorry reabsorption obligatory water reabsorption is reabsorption that is always going to be reabsorbed and that based on where it's being reabsorbed we really can't change how much is reabsorbed in those places obligatory it's obligated those parts of the nephron are obligated to reabsorb water and the volume of re and the amount and quantity that they reabsorb can't be changed essentially. However, facultative water reabsorption is the process where we can adjust in certain places of the nephron the volume of water that gets reabsorbed. Now 85% of the water in the filtrate, so 85% of that 99% that gets reabsorbed, is reabsorbed in the proximal convoluted tubule and the nephron loop or the loop of Henle. That is all obligatory water loss. We can't change homeostatically. We cannot change the amount of water that's reabsorbed from those two places. We can with external means like medications. We can affect the amount of water reabsorbed, but we're not talking about that. We're talking about homeostatically, biologically. Which means then that the other 15% of water reabsorption that occurs is going to occur due to the facultative process in places where we can actually adjust that volume. That is the distal convoluted tubule, excuse me, and the collecting duct. And the collecting duct is not part of the nephron, but it is an important structure related to them because all those distal convoluted tubules feed into those collecting ducts. Remember the renal papilla? If you look at a... The very end of the renal pyramid where it feeds into that renal calyx. The renal papilla really are those openings to all of those collecting ducts. and they then empty into the minor calyx or major calyx into the renal pelvis and eventually out. So we're going to kind of follow sodium and chloride and water here. We talked about filtration, reabsorption and secretion are the other two processes, so we're going to focus on reabsorption. So obviously we have to reabsorb water. Water reabsorption is always going to occur by osmosis, meaning that there has to be some type of concentration, a solute difference. The concentration of solutes on one side of a membrane or the other has to be different because that's how osmosis works. Water's gonna move to where the solute concentration is higher. And our main solute is sodium. Keep in the back of your mind that where sodium goes, water is going to go. Wherever sodium goes in the reabsorption process, water is going to leave there as well. Most sodium is kind of actively transported out, more like secondary active transport, if you remember what that is. I'll show you. All right, so this is a picture from the book. This is what's happening in the proximal convoluted tubule. So here is the filtrate, okay, the lumen of the proximal convoluted tubule. The filtrate is going down this way. Here are the cells that make up the tube. We have these tight cell junctions here. There is some movement of sodium and other things through these. It's called... Paracellular reabsorption. We're really not going to focus on that one. We got to focus on these active mechanisms of sodium reabsorption So you can see here is that sodium is more concentrated outside the cell than inside the cell, but there's a reason for that is that over here on what we call the basolateral surface or basal surface, I don't want to say the bottom of the cell, but we could look at it that way. Think of that this over here would be the blood vessels where these things that are being reabsorbed are going into. So this basal surface here, we have the sodium potassium pump. We know that requires ATP, and we know that three sodium are going to leave the cell. How many potassium are going to be brought in? Two. So this pump is constantly working to keep as much sodium as it can out of the inside of the cell and pushing that into this interstitial fluid and eventually into the blood. That allows sodium. to move down its concentration gradient back into the cell. This is important because sodium is used in a co-transport mechanism to bring glucose or special glucose transporters that are powered by sodium. And glucose can't get into the cell on its own. it has to use the energy of something else. So we're using the concentration gradient of sodium to bring glucose into the cell. That only works if the concentration of sodium in the cell is lower than the concentration outside. And that sodium-potassium pump is what powers that process. This is called secondary active transport. Remember that? So we have to have the sodium-potassium pump, which is primary active transport. to create the gradient that allows sodium to diffuse down its gradient and bring in glucose at the same time. We also have this counter transport process where sodium can be moved in and hydrogen ions are moved out at the same time. That is not an active process. It doesn't require energy directly, but again we have to rely on a sodium gradient being created. I'm going to come back and talk about the sodium glucose transporter shortly. And you can see that that glucose is actually able to pass out through its own gradient through facilitated diffusion. Remember that? where there's another molecule that physically helps it move down its gradient. And then potassium obviously can leave through these leak channels on its own, but then it gets pumped back in, maintaining that gradient. That's how sodium gets reabsorbed in the proximal convoluted tubule. Now water is going to follow that sodium. Water can actually follow through these tight junctions in a paracellular process. There's also ways to get water into those cells as well. But water through the paracellular process is big because this interstitial fluid here is going to have a high solute concentration in it. And so water by osmosis. we'll be able to move that way. So that's the sodium reabsorption in the proximal convoluted tubule. Now we also have sodium reabsorption occurring in the ascending limb of the loop of Henle. Now remember if you looked at the loop of Henle, we have this thick and thin limb. very good but so the filtrate is going to be coming down here so let's say that this is the cortex and this is the medulla here's our thin limb Oh, good grief. Well, anyway, you should know the anatomy. I'm not going to draw it. So in that ascending limb, it is impermeable to water. Water does not leave the filtrate through the ascending limb. Water only leaves via the descending limb. But that ascending limb is important because, remember I said, water is going to leave the filter at biosposis, which means that there has to be a solute concentration somewhere. So what happens is that the solutes that are moving up that ascending limb of the nephron loop towards that distal convoluted tubule, the sodium and chloride that hasn't been reabsorbed, that the cells of that ascending limb, those are the ones that are pulling the sodium from the filtrate. They're putting it inside the cell. Again, what do we have here? Sodium-potassium pump maintaining a sodium gradient. So sodium is able to actually move down its gradient into the cells of the ascending limb of lupafenil. At the same time, it brings potassium in with it. pulling potassium against its own gradient and chloride actually moves in via an electrostatic. It's attracted and kind of gets pulled in at the same time because of its attraction to the positively charged sodium. So this is a sodium potassium chloride co-transport protein NKCC. Don't worry about knowing that name. Just know that there's transporters that are going to pull. sodium and chloride and potassium from the filtrate into that ascending limb cell. And then on the basal surface again, we have the sodium potassium pump getting that sodium out. We have chloride channels allowing chloride to simply diffuse down its own gradient. And the sodium and the chloride here stay in that renal medulla. This is in the renal medulla. If you didn't catch that from that drawing, I tried it. This is in the renal medulla. Those salts, that sodium and the chloride stay in there. That is what's going to allow the water to be pulled from the filtrate as it goes down that descending limb and end up back into the blood. And that's part of the process called the countercurrent multiple. fire system, which is in another section. And I'll go over that with you. Okay, so really what all this was talking about was how sodium is being reabsorbed and where. Okay, really it's reabsorbed exactly the same way. In this case, in the proximal convoluted tubule, it goes into the blood, it stays there. But over here, it stays in the medulla and concentrates. the renal medulla so that it's salty. I think I mentioned that last time. I've never eaten kidney, but I imagine it to be salty because of this process right here, keeping those salts in that medulla. Now, if we looked at the collecting duct, we're going to come back later and talk about the distal convoluted tubule. We see something similar. Okay, so this is now the collecting duct. We have the, at this point, it's urine. The urine, as it's making its way to the renal calyx through the collecting duct, there are sodium channels that allow that sodium to leave. Obviously, we don't take all the sodium from the urine in this case here. But sodium diffuses down its own gradient and then is pumped out again. with that sodium potassium pump into that renal medulla. Some of that is reabsorbed into the blood, but some stays in the medulla, keeping that solute concentration high. Now, this is going to be important later in the next section when we look at water reabsorption, because it's this concentrated interstitial fluid in the renal medulla. That is going to allow water to leave by osmosis. And we want to reabsorb that water. We need to reabsorb about 99%. Otherwise, you're going to urinate yourself to death. You'll dehydrate within a matter of hours if you don't reabsorb your water. Ask anybody that has diabetes insipidus. Anybody know what that is? It is an... A condition where the body is not producing anti-diuretic hormone and people are not able to reabsorb water from the collecting duct. So they got to urinate like every hour and they have to keep drinking water and fluids to stay hydrated. There was a professor here years ago that told me that she had a lot of health problems. She always made sure everybody knew that. She's no longer here for a variety of reasons. So she told me at one point she had this. And it was like to the point where she wanted to kill herself because she just couldn't handle it. Literally every hour or more or sooner, she was getting up to go to the bathroom in the middle of the night. She couldn't sleep just because there's no water reabsorption taking place. So that is a real thing. Now that's different from diabetes, mellitus, the glucose, where people can't get the insulin issues. That causes increased urinary output because of what having the extra glucose does and how that affects the osmotic gradient, keeping water in the urine and not moving out by osmosis where it should. That's where diabetes comes in. Okay. What's this here? Oh, yeah. Okay. So this is kind of a little bit about what happens in the collecting duct. And I really like this book a lot. I'm not sure why they put some of the logic in putting some of the things where there are. But what they're talking about here, also in this section, is the water reabsorption that takes place in the collecting duct. And there are special protein cells, protein structures, in the cells of the collecting duct called aquaporins. water channels. And there's always a certain number of these protein channels that allow water to move through them. Now the water can easily diffuse down its gradient into the cell and then out the other side because this medulla here is salty. There's a higher solute concentration. So again, we always have a certain amount of these. But sometimes we need to reabsorb more water from the collecting duct. And if we want to reabsorb more water from the collecting duct, we have to add more aquaporins. And antidiuretic hormone, which comes from the posterior pituitary gland, is the stimulating factor for adding more aquaporins to these cells of the collecting duct. Now if water moves passively because of osmosis, what's the limiting factor in how much water actually is reabsorbed? What limits the volume of water that's removed from the collecting duct back into the blood? How can we increase the volume of water leaving the collecting duct going back into the blood? having more aquaporins. So the number of aquaporins is the limiting factor, what limits the amount of water. So if we can increase the number of aquaporins, we can get more water. All right. And so this is what the antidiuretic hormone does. All right. So here's a receptor. And that receptor is a G, if it's a dentalate cyclase, remember, that's a G coupled protein receptor converting ATP to cyclic AMP, which activates Protein kinase A, is that all coming back to you now? Okay. Which then stimulates the membrane fusion of these vesicles that already have these aquaporins in them. And that vesicle fuses with that cell membrane, but basically like exocytosis, except it's not releasing anything. And so now we have extra aquaporins, and so we can increase water reabsorption. Let's look at that second graph. I'm going to add another slide here. So let's look at a couple things here. So let's say that this is our baseline levels of antidiuretic hormone. And that's our set point. And this color here, this blue, represents water reabsorption in the collecting duct. And at that baseline level, you know, we're always fluctuating up and down slightly. And what this also means is that we have to continually release a certain amount of anti-diuretic hormone to maintain a certain amount of reabsorption. So if you saw this on the graph that we saw. Sorry, that doesn't make sense over here. So this is water reabsorption on the y-axis. My fault. So if we saw an increase in water reabsorption, what should that tell you about the amount of antidiuretic hormone circulating in the blood and about the number of aquaporins in the collecting duct cells? If we saw the amount of water reabsorption in the collecting duct rise, reabsorbing more water. Started at this point here. What's that telling you about A, the level of antidiuretic hormone, and B, the number of aquaporins? Well, if increased water reabsorption is happening, water only can move through those aquaporins. Aquaporins are the limiting factor, so if we're increasing the amount of water reabsorption, there has to be more aquaporins there. How does more aquaporins get there? Increasing the amount of ADH. So then if you saw this, what does that tell you that's happening? Do my purple arrow again. So if we're starting to see this water reabsorption collecting duct decrease, well, now we're starting to see a decrease in the number of aquaporins due to a decrease in the amount of anti-diuretic hormone. And so depending on the needs of the body, Anti-diuretic hormone will be released. Now the stimulus for that is solute concentration of the blood. I'm going to draw brackets around solute because brackets is way of indicating concentration. Solute concentration of the blood is the stimulus for changing the amount of antidiuretic hormone that's released. Remember we said the maculodensa is a type of osmoreceptor? Well, this is not what triggers the release of ADH. In the hypothalamus, there are osmoreceptors. And if we have an increased osmolarity of the blood, that equates to a decrease in blood volume. Blood volume is going to be lower, not enough water in the blood. So what is one way? that we can get more water in the blood fairly quickly? Well, we can get it. We're filtering a lot of water through the kidneys, and there are ways to change that facultative reabsorption in the distal convoluted tubule in the collecting duct. So if we increase the amount of aquaporins due to increased antidiuretic hormone, then we can put more water back into the blood. And that ratio of salts to water changes, and now the blood won't be as concentrated with solutes because we added water back to it. It's like taking a gallon of water and mixing with it a pound of salt. You've got that ratio, right? One pound to one gallon. But if you take out a half, if you boil away a half gallon of water, it's more concentrated with salt. So you haven't changed the amount of salts. You change the water, which effectively changes the ratio. So we're not necessarily going to get rid of salts, although we may in certain ways, but really we have to add more water. And so the collecting duct will allow more water to be reabsorbed from the filtrate, put back into the blood. So if you're like one of those days, you just are so busy, you don't have really time to drink your normal amount of water, you're busy, you don't really go to the restroom till like five o'clock. go to the bathroom one time and it's really that concentrated urine okay and not a lot of it you're kind of dehydrated so your body would then be increasing the number of aquaporins because you don't have enough water in your blood because you're not consuming to allow more water to reabsorb therefore your urine volume will change now let's add this to our graph because changes in the number of aquaporins changes in the anti-diuretic hormone will in turn affect the volume of urine and the concentration of solutes in the urine. And it's an inverse relationship. So if the green represents urine volume, I'm just going to draw a straight line at this point. If we increase the number of aquaporins, which means that we increase the amount of water reabsorption, what happens to essentially the volume of urine we're producing? It's an inverse relationship. The more water you reabsorb from the collecting duct, the less urine you're going to have. It's going to decrease. It's an inverse relationship. As aquaporin numbers or antidiuretic hormone levels go up, the urine volume goes down. There's less water in your urine because more of that water that would normally be in your urine is getting reabsorbed back into the blood because there's not enough water in your blood. And so as the volume of water reabsorbed gets less, that means that the amount of water in our urine goes up. Now the amount of sodium and potassium that are in our urine for the most part at this point are pretty fixed. There isn't a lot of ways to change the amount of sodium and potassium in our urine once it's in the collecting duct. So what can we say about the concentration of solutes in our urine at the same time? If we were to measure the sodium and potassium or sodium specifically in our urine during this process. How would we see the relative concentrations of sodium change in response to the change in ADH level? Well, the water is getting reabsorbed, so the volume of water in our urine is less, but is there anything happening with the sodium? What did I just say over here? That once that filtrate is in the collecting duct, the amount of sodium and potassium that's being pulled and added to the filtrate doesn't really change. It's pretty much at a steady rate. So if this isn't changing, but the amount of water in the urine is changing, What that means then, if this is salt concentration, that as water is reabsorbed, we're going to see a rise in the amount of solutes in our urine. It's going to be like boiling the water away, but leaving the salt in the pot. And then eventually, as the amount of water reabsorbed gets less, well then the... relative amount of solutes in that urine is going to go down. So you can look at it like we're not really changing the amount of salt in there, but by reducing the amount of the ratio of water to salt, we have more salt. It's saltier. That's the idea. So we're not really removing the sodium, but we're changing the amount of water that's in there. But think of that. Pot on the stove with a pound of salt and a gallon of water. If I remove half the water, boil away half the water and keep the salt in there, if you were to taste that water after that, it's going to taste even saltier because we got rid of that water. That's what's happening with the urine. We're not changing the salts in the urine, but by removing that water, it's concentrating the amount of salts that are normally there. All right, and that's kind of what this slide is talking about here. You should have read about that. This is talking about antidiuretic hormone, concentrated urine. All right, I want to talk about glucose here and amino acids, but mainly glucose. Both of those are pretty easily filtered because they're small enough. But we don't want glucose in our urine. There shouldn't be glucose in our urine if we're healthy. And that's because in the urine, as I mentioned, or in the proximal convoluted tubule, in fact, all glucose should be fully reabsorbed by the time that filtrate reaches the loop of Henle. And there are what we call sodium glucose transporters. I mentioned that earlier, they are co-transport. It is a secondary active transport, meaning that on this basal surface here, basolateral membrane, here's the blood vessels, so here's the filtrate coming down this way. We're pumping. Sodium out into the blood. Potassium is secreted out and actually goes into the cells and then actually comes back out again. But we're maintaining that sodium gradient inside the cell. That's what the active transport pump does, the sodium-potassium pump. That allows sodium. to move down its gradient and using the energy in that gradient bring glucose in with it using this special transport protein. Now that's all fine and dandy. There is a fixed number of these transporters. There is no way for our body to homeostatically decrease or decrease the number of those. I don't know how many there are, you know, cubic nanometer of a cell. That's not important, but they're fixed. So if you have way too much glucose, and basically they kind of work one at a time, you can't get another glucose in until the previous one has gone in. So if you suddenly see a pretty big increase in the amount of glucose in your blood, And your insulin isn't working to stimulate the movement of glucose into your body cells so that they can use them as a fuel source, energy source. That means you're going to have a lot more glucose being filtered out in your urine. And because there's a fixed number of these transporters, if you have way more glucose in your urine, then there are transporters to move them all. out of the filtrate back into your blood, you're going to end up with glucose in your urine. Okay, so it gets to a point where there's what we call a transport maximum. Your book has a graph in there. I didn't mean to do that. I think I did. Page 501, it's kind of confusing. I didn't particularly like it. But basically, when you reach about 400 milligrams of glucose per minute being filtered out of your blood, that's the maximum amount of reabsorption that can occur. If you're filtering out more than 400 milligrams of glucose... per minute from your filtrate, you're going to end up with that in your urine. The difference, okay? Not all of it, but just the difference. On the bottom of the graph, they say normally there's about, you know, 100 milligrams for every 100 milliliters of blood. There's about we can reabsorb it all. And then if you follow that graph, the threshold is about 200. So once our blood sugar gets to about 200 milligrams per deciliter or 100 milliliters of blood, that's when we've kind of reached that maximum. We can't really reabsorb all of that. And that's what ends up in our urine. So we have a transport maximum. We're limited in how much glucose can be reabsorbed. by the number of transport molecules. All right. Just make a note here that reabsorption of water through the proximal convoluted tubule, remember this is obligatory, that we can't change the amount of water reabsorbed in that proximal convoluted tubule. And then secretion, that is a process where things leave the blood and go into where the filter is. So it can leave via the urine. One of the things... a lot of prescription medication or drugs in general, prescription or non, and the byproducts of metabolizing those drugs end up in the urine. That's why in a urine test, they can detect marijuana and whatever, certain kinds of things or others, because they may not get filtered from the blood, but they're added to the filtrate by the blood through the secretion process. There are mechanisms where we can change the amount of hydrogen ions in the blood by getting rid of. If blood pH is too low, it's too acidic, we can secrete hydrogen ions from the blood and put them in the filtrate to help manage pH.

Yeah. We do actually get glucose in our filtrate, but in a healthy individual, that glucose should all be reabsorbed and you should not have glucose in your urine. We'll talk about that transport process shortly.

And then urea is one of the major waste products that we're trying to get rid of through this process. Notice that some is actually reabsorbed and that's okay. that does kind of help manage some pH. It also does play a role in maintaining an osmotic gradient in the medulla as well, but we do excrete about 30 grams of that per day.

We absorb about 44 percent, but anyway don't memorize those numbers they're just kind of for reference. Now if we're producing 180 liters a day, and I don't think this was on the video, This is more section 13. Still that same. Yeah, I think this is still section three. But we have to obviously reabsorb that.

I want to make sure you understand that there's two kinds of reabsorption specifically for water. And we're really only going to focus on water and sodium and look at. those mechanisms for getting those back in, and glucose. That's really what we're going to look at. So there's two kinds of water reabsorption.

There's what we call obligatory and facultative. Obligatory water loss is water that is always going to be... or sorry reabsorption obligatory water reabsorption is reabsorption that is always going to be reabsorbed and that based on where it's being reabsorbed we really can't change how much is reabsorbed in those places obligatory it's obligated those parts of the nephron are obligated to reabsorb water and the volume of re and the amount and quantity that they reabsorb can't be changed essentially. However, facultative water reabsorption is the process where we can adjust in certain places of the nephron the volume of water that gets reabsorbed. Now 85% of the water in the filtrate, so 85% of that 99% that gets reabsorbed, is reabsorbed in the proximal convoluted tubule and the nephron loop or the loop of Henle.

That is all obligatory water loss. We can't change homeostatically. We cannot change the amount of water that's reabsorbed from those two places.

We can with external means like medications. We can affect the amount of water reabsorbed, but we're not talking about that. We're talking about homeostatically, biologically. Which means then that the other 15% of water reabsorption that occurs is going to occur due to the facultative process in places where we can actually adjust that volume.

That is the distal convoluted tubule, excuse me, and the collecting duct. And the collecting duct is not part of the nephron, but it is an important structure related to them because all those distal convoluted tubules feed into those collecting ducts. Remember the renal papilla? If you look at a...

The very end of the renal pyramid where it feeds into that renal calyx. The renal papilla really are those openings to all of those collecting ducts. and they then empty into the minor calyx or major calyx into the renal pelvis and eventually out. So we're going to kind of follow sodium and chloride and water here. We talked about filtration, reabsorption and secretion are the other two processes, so we're going to focus on reabsorption.

So obviously we have to reabsorb water. Water reabsorption is always going to occur by osmosis, meaning that there has to be some type of concentration, a solute difference. The concentration of solutes on one side of a membrane or the other has to be different because that's how osmosis works. Water's gonna move to where the solute concentration is higher. And our main solute is sodium.

Keep in the back of your mind that where sodium goes, water is going to go. Wherever sodium goes in the reabsorption process, water is going to leave there as well. Most sodium is kind of actively transported out, more like secondary active transport, if you remember what that is. I'll show you.

All right, so this is a picture from the book. This is what's happening in the proximal convoluted tubule. So here is the filtrate, okay, the lumen of the proximal convoluted tubule.

The filtrate is going down this way. Here are the cells that make up the tube. We have these tight cell junctions here. There is some movement of sodium and other things through these.

It's called... Paracellular reabsorption. We're really not going to focus on that one.

We got to focus on these active mechanisms of sodium reabsorption So you can see here is that sodium is more concentrated outside the cell than inside the cell, but there's a reason for that is that over here on what we call the basolateral surface or basal surface, I don't want to say the bottom of the cell, but we could look at it that way. Think of that this over here would be the blood vessels where these things that are being reabsorbed are going into. So this basal surface here, we have the sodium potassium pump. We know that requires ATP, and we know that three sodium are going to leave the cell.

How many potassium are going to be brought in? Two. So this pump is constantly working to keep as much sodium as it can out of the inside of the cell and pushing that into this interstitial fluid and eventually into the blood.

That allows sodium. to move down its concentration gradient back into the cell. This is important because sodium is used in a co-transport mechanism to bring glucose or special glucose transporters that are powered by sodium. And glucose can't get into the cell on its own.

it has to use the energy of something else. So we're using the concentration gradient of sodium to bring glucose into the cell. That only works if the concentration of sodium in the cell is lower than the concentration outside.

And that sodium-potassium pump is what powers that process. This is called secondary active transport. Remember that?

So we have to have the sodium-potassium pump, which is primary active transport. to create the gradient that allows sodium to diffuse down its gradient and bring in glucose at the same time. We also have this counter transport process where sodium can be moved in and hydrogen ions are moved out at the same time.

That is not an active process. It doesn't require energy directly, but again we have to rely on a sodium gradient being created. I'm going to come back and talk about the sodium glucose transporter shortly. And you can see that that glucose is actually able to pass out through its own gradient through facilitated diffusion.

Remember that? where there's another molecule that physically helps it move down its gradient. And then potassium obviously can leave through these leak channels on its own, but then it gets pumped back in, maintaining that gradient.

That's how sodium gets reabsorbed in the proximal convoluted tubule. Now water is going to follow that sodium. Water can actually follow through these tight junctions in a paracellular process.

There's also ways to get water into those cells as well. But water through the paracellular process is big because this interstitial fluid here is going to have a high solute concentration in it. And so water by osmosis.

we'll be able to move that way. So that's the sodium reabsorption in the proximal convoluted tubule. Now we also have sodium reabsorption occurring in the ascending limb of the loop of Henle. Now remember if you looked at the loop of Henle, we have this thick and thin limb.

very good but so the filtrate is going to be coming down here so let's say that this is the cortex and this is the medulla here's our thin limb Oh, good grief. Well, anyway, you should know the anatomy. I'm not going to draw it. So in that ascending limb, it is impermeable to water. Water does not leave the filtrate through the ascending limb.

Water only leaves via the descending limb. But that ascending limb is important because, remember I said, water is going to leave the filter at biosposis, which means that there has to be a solute concentration somewhere. So what happens is that the solutes that are moving up that ascending limb of the nephron loop towards that distal convoluted tubule, the sodium and chloride that hasn't been reabsorbed, that the cells of that ascending limb, those are the ones that are pulling the sodium from the filtrate. They're putting it inside the cell.

Again, what do we have here? Sodium-potassium pump maintaining a sodium gradient. So sodium is able to actually move down its gradient into the cells of the ascending limb of lupafenil.

At the same time, it brings potassium in with it. pulling potassium against its own gradient and chloride actually moves in via an electrostatic. It's attracted and kind of gets pulled in at the same time because of its attraction to the positively charged sodium.

So this is a sodium potassium chloride co-transport protein NKCC. Don't worry about knowing that name. Just know that there's transporters that are going to pull. sodium and chloride and potassium from the filtrate into that ascending limb cell. And then on the basal surface again, we have the sodium potassium pump getting that sodium out.

We have chloride channels allowing chloride to simply diffuse down its own gradient. And the sodium and the chloride here stay in that renal medulla. This is in the renal medulla. If you didn't catch that from that drawing, I tried it.

This is in the renal medulla. Those salts, that sodium and the chloride stay in there. That is what's going to allow the water to be pulled from the filtrate as it goes down that descending limb and end up back into the blood.

And that's part of the process called the countercurrent multiple. fire system, which is in another section. And I'll go over that with you. Okay, so really what all this was talking about was how sodium is being reabsorbed and where.

Okay, really it's reabsorbed exactly the same way. In this case, in the proximal convoluted tubule, it goes into the blood, it stays there. But over here, it stays in the medulla and concentrates.

the renal medulla so that it's salty. I think I mentioned that last time. I've never eaten kidney, but I imagine it to be salty because of this process right here, keeping those salts in that medulla. Now, if we looked at the collecting duct, we're going to come back later and talk about the distal convoluted tubule. We see something similar.

Okay, so this is now the collecting duct. We have the, at this point, it's urine. The urine, as it's making its way to the renal calyx through the collecting duct, there are sodium channels that allow that sodium to leave. Obviously, we don't take all the sodium from the urine in this case here.

But sodium diffuses down its own gradient and then is pumped out again. with that sodium potassium pump into that renal medulla. Some of that is reabsorbed into the blood, but some stays in the medulla, keeping that solute concentration high.

Now, this is going to be important later in the next section when we look at water reabsorption, because it's this concentrated interstitial fluid in the renal medulla. That is going to allow water to leave by osmosis. And we want to reabsorb that water.

We need to reabsorb about 99%. Otherwise, you're going to urinate yourself to death. You'll dehydrate within a matter of hours if you don't reabsorb your water.

Ask anybody that has diabetes insipidus. Anybody know what that is? It is an...

A condition where the body is not producing anti-diuretic hormone and people are not able to reabsorb water from the collecting duct. So they got to urinate like every hour and they have to keep drinking water and fluids to stay hydrated. There was a professor here years ago that told me that she had a lot of health problems. She always made sure everybody knew that. She's no longer here for a variety of reasons.

So she told me at one point she had this. And it was like to the point where she wanted to kill herself because she just couldn't handle it. Literally every hour or more or sooner, she was getting up to go to the bathroom in the middle of the night.

She couldn't sleep just because there's no water reabsorption taking place. So that is a real thing. Now that's different from diabetes, mellitus, the glucose, where people can't get the insulin issues. That causes increased urinary output because of what having the extra glucose does and how that affects the osmotic gradient, keeping water in the urine and not moving out by osmosis where it should.

That's where diabetes comes in. Okay. What's this here?

Oh, yeah. Okay. So this is kind of a little bit about what happens in the collecting duct. And I really like this book a lot.

I'm not sure why they put some of the logic in putting some of the things where there are. But what they're talking about here, also in this section, is the water reabsorption that takes place in the collecting duct. And there are special protein cells, protein structures, in the cells of the collecting duct called aquaporins.

water channels. And there's always a certain number of these protein channels that allow water to move through them. Now the water can easily diffuse down its gradient into the cell and then out the other side because this medulla here is salty. There's a higher solute concentration.

So again, we always have a certain amount of these. But sometimes we need to reabsorb more water from the collecting duct. And if we want to reabsorb more water from the collecting duct, we have to add more aquaporins. And antidiuretic hormone, which comes from the posterior pituitary gland, is the stimulating factor for adding more aquaporins to these cells of the collecting duct. Now if water moves passively because of osmosis, what's the limiting factor in how much water actually is reabsorbed?

What limits the volume of water that's removed from the collecting duct back into the blood? How can we increase the volume of water leaving the collecting duct going back into the blood? having more aquaporins.

So the number of aquaporins is the limiting factor, what limits the amount of water. So if we can increase the number of aquaporins, we can get more water. All right.

And so this is what the antidiuretic hormone does. All right. So here's a receptor.

And that receptor is a G, if it's a dentalate cyclase, remember, that's a G coupled protein receptor converting ATP to cyclic AMP, which activates Protein kinase A, is that all coming back to you now? Okay. Which then stimulates the membrane fusion of these vesicles that already have these aquaporins in them. And that vesicle fuses with that cell membrane, but basically like exocytosis, except it's not releasing anything. And so now we have extra aquaporins, and so we can increase water reabsorption.

Let's look at that second graph. I'm going to add another slide here. So let's look at a couple things here. So let's say that this is our baseline levels of antidiuretic hormone.

And that's our set point. And this color here, this blue, represents water reabsorption in the collecting duct. And at that baseline level, you know, we're always fluctuating up and down slightly.

And what this also means is that we have to continually release a certain amount of anti-diuretic hormone to maintain a certain amount of reabsorption. So if you saw this on the graph that we saw. Sorry, that doesn't make sense over here. So this is water reabsorption on the y-axis. My fault.

So if we saw an increase in water reabsorption, what should that tell you about the amount of antidiuretic hormone circulating in the blood and about the number of aquaporins in the collecting duct cells? If we saw the amount of water reabsorption in the collecting duct rise, reabsorbing more water. Started at this point here.

What's that telling you about A, the level of antidiuretic hormone, and B, the number of aquaporins? Well, if increased water reabsorption is happening, water only can move through those aquaporins. Aquaporins are the limiting factor, so if we're increasing the amount of water reabsorption, there has to be more aquaporins there. How does more aquaporins get there? Increasing the amount of ADH.

So then if you saw this, what does that tell you that's happening? Do my purple arrow again. So if we're starting to see this water reabsorption collecting duct decrease, well, now we're starting to see a decrease in the number of aquaporins due to a decrease in the amount of anti-diuretic hormone.

And so depending on the needs of the body, Anti-diuretic hormone will be released. Now the stimulus for that is solute concentration of the blood. I'm going to draw brackets around solute because brackets is way of indicating concentration.

Solute concentration of the blood is the stimulus for changing the amount of antidiuretic hormone that's released. Remember we said the maculodensa is a type of osmoreceptor? Well, this is not what triggers the release of ADH. In the hypothalamus, there are osmoreceptors. And if we have an increased osmolarity of the blood, that equates to a decrease in blood volume.

Blood volume is going to be lower, not enough water in the blood. So what is one way? that we can get more water in the blood fairly quickly?

Well, we can get it. We're filtering a lot of water through the kidneys, and there are ways to change that facultative reabsorption in the distal convoluted tubule in the collecting duct. So if we increase the amount of aquaporins due to increased antidiuretic hormone, then we can put more water back into the blood. And that ratio of salts to water changes, and now the blood won't be as concentrated with solutes because we added water back to it. It's like taking a gallon of water and mixing with it a pound of salt.

You've got that ratio, right? One pound to one gallon. But if you take out a half, if you boil away a half gallon of water, it's more concentrated with salt. So you haven't changed the amount of salts.

You change the water, which effectively changes the ratio. So we're not necessarily going to get rid of salts, although we may in certain ways, but really we have to add more water. And so the collecting duct will allow more water to be reabsorbed from the filtrate, put back into the blood. So if you're like one of those days, you just are so busy, you don't have really time to drink your normal amount of water, you're busy, you don't really go to the restroom till like five o'clock. go to the bathroom one time and it's really that concentrated urine okay and not a lot of it you're kind of dehydrated so your body would then be increasing the number of aquaporins because you don't have enough water in your blood because you're not consuming to allow more water to reabsorb therefore your urine volume will change now let's add this to our graph because changes in the number of aquaporins changes in the anti-diuretic hormone will in turn affect the volume of urine and the concentration of solutes in the urine.

And it's an inverse relationship. So if the green represents urine volume, I'm just going to draw a straight line at this point. If we increase the number of aquaporins, which means that we increase the amount of water reabsorption, what happens to essentially the volume of urine we're producing? It's an inverse relationship. The more water you reabsorb from the collecting duct, the less urine you're going to have.

It's going to decrease. It's an inverse relationship. As aquaporin numbers or antidiuretic hormone levels go up, the urine volume goes down. There's less water in your urine because more of that water that would normally be in your urine is getting reabsorbed back into the blood because there's not enough water in your blood. And so as the volume of water reabsorbed gets less, that means that the amount of water in our urine goes up.

Now the amount of sodium and potassium that are in our urine for the most part at this point are pretty fixed. There isn't a lot of ways to change the amount of sodium and potassium in our urine once it's in the collecting duct. So what can we say about the concentration of solutes in our urine at the same time? If we were to measure the sodium and potassium or sodium specifically in our urine during this process. How would we see the relative concentrations of sodium change in response to the change in ADH level?

Well, the water is getting reabsorbed, so the volume of water in our urine is less, but is there anything happening with the sodium? What did I just say over here? That once that filtrate is in the collecting duct, the amount of sodium and potassium that's being pulled and added to the filtrate doesn't really change.

It's pretty much at a steady rate. So if this isn't changing, but the amount of water in the urine is changing, What that means then, if this is salt concentration, that as water is reabsorbed, we're going to see a rise in the amount of solutes in our urine. It's going to be like boiling the water away, but leaving the salt in the pot.

And then eventually, as the amount of water reabsorbed gets less, well then the... relative amount of solutes in that urine is going to go down. So you can look at it like we're not really changing the amount of salt in there, but by reducing the amount of the ratio of water to salt, we have more salt. It's saltier. That's the idea.

So we're not really removing the sodium, but we're changing the amount of water that's in there. But think of that. Pot on the stove with a pound of salt and a gallon of water. If I remove half the water, boil away half the water and keep the salt in there, if you were to taste that water after that, it's going to taste even saltier because we got rid of that water.

That's what's happening with the urine. We're not changing the salts in the urine, but by removing that water, it's concentrating the amount of salts that are normally there. All right, and that's kind of what this slide is talking about here.

You should have read about that. This is talking about antidiuretic hormone, concentrated urine. All right, I want to talk about glucose here and amino acids, but mainly glucose. Both of those are pretty easily filtered because they're small enough.

But we don't want glucose in our urine. There shouldn't be glucose in our urine if we're healthy. And that's because in the urine, as I mentioned, or in the proximal convoluted tubule, in fact, all glucose should be fully reabsorbed by the time that filtrate reaches the loop of Henle.

And there are what we call sodium glucose transporters. I mentioned that earlier, they are co-transport. It is a secondary active transport, meaning that on this basal surface here, basolateral membrane, here's the blood vessels, so here's the filtrate coming down this way. We're pumping.

Sodium out into the blood. Potassium is secreted out and actually goes into the cells and then actually comes back out again. But we're maintaining that sodium gradient inside the cell. That's what the active transport pump does, the sodium-potassium pump.

That allows sodium. to move down its gradient and using the energy in that gradient bring glucose in with it using this special transport protein. Now that's all fine and dandy.

There is a fixed number of these transporters. There is no way for our body to homeostatically decrease or decrease the number of those. I don't know how many there are, you know, cubic nanometer of a cell.

That's not important, but they're fixed. So if you have way too much glucose, and basically they kind of work one at a time, you can't get another glucose in until the previous one has gone in. So if you suddenly see a pretty big increase in the amount of glucose in your blood, And your insulin isn't working to stimulate the movement of glucose into your body cells so that they can use them as a fuel source, energy source.

That means you're going to have a lot more glucose being filtered out in your urine. And because there's a fixed number of these transporters, if you have way more glucose in your urine, then there are transporters to move them all. out of the filtrate back into your blood, you're going to end up with glucose in your urine. Okay, so it gets to a point where there's what we call a transport maximum. Your book has a graph in there.

I didn't mean to do that. I think I did. Page 501, it's kind of confusing. I didn't particularly like it.

But basically, when you reach about 400 milligrams of glucose per minute being filtered out of your blood, that's the maximum amount of reabsorption that can occur. If you're filtering out more than 400 milligrams of glucose... per minute from your filtrate, you're going to end up with that in your urine. The difference, okay? Not all of it, but just the difference.

On the bottom of the graph, they say normally there's about, you know, 100 milligrams for every 100 milliliters of blood. There's about we can reabsorb it all. And then if you follow that graph, the threshold is about 200. So once our blood sugar gets to about 200 milligrams per deciliter or 100 milliliters of blood, that's when we've kind of reached that maximum.

We can't really reabsorb all of that. And that's what ends up in our urine. So we have a transport maximum. We're limited in how much glucose can be reabsorbed. by the number of transport molecules.

All right. Just make a note here that reabsorption of water through the proximal convoluted tubule, remember this is obligatory, that we can't change the amount of water reabsorbed in that proximal convoluted tubule. And then secretion, that is a process where things leave the blood and go into where the filter is.

So it can leave via the urine. One of the things... a lot of prescription medication or drugs in general, prescription or non, and the byproducts of metabolizing those drugs end up in the urine. That's why in a urine test, they can detect marijuana and whatever, certain kinds of things or others, because they may not get filtered from the blood, but they're added to the filtrate by the blood through the secretion process. There are mechanisms where we can change the amount of hydrogen ions in the blood by getting rid of.

If blood pH is too low, it's too acidic, we can secrete hydrogen ions from the blood and put them in the filtrate to help manage pH.

Transcript for:Kidney Filtration and Reabsorption Overview

Transcript for:
Kidney Filtration and Reabsorption Overview