Renal protein reabsorption

Transcription

What I want to do in this video is talk a little bit about the kidney-- and this is a big picture of a kidney-- and to talk about how it operates at its-- I guess you could call it its smallest functional level and that's the nephron. So we're going to talk about the kidney and the nephron. And I think you might already know the kidney. We have two of them. They're the organ that, I guess, is most famous for producing or allowing us to excrete waste. But part of that process, it also helps us maintain our water, the correct level, and actually the amount of salts or electrolytes we have and our blood pressure, but I'll just say maintain water. And it also produces hormones and things, and I'm not going to go into a lot of detail on that right now. I really just want to focus on these first two to kind of just understand the overview function of the kidney. And most of us have two of these. They're kind of closer to our back on either sides of our spine behind our liver. And this is a zoomed-in version of it. If you're watching this in full screen, it's not going to be as big as this picture is, but we've sliced it so we can see what's going on inside the kidney. Just to understand the different parts here, just because it will actually be significant when we start talking about the functional units or the nephron within the kidney, this area right here from here to here, this is called the renal cortex. Whenever we talk about something with the kidney, if you see a renal anything, that's actually referring to the kidney. So this right here is a renal cortex, that outer part right there. And then this area right here, this is the renal medulla. And medulla comes from middle. So you can almost view it as the middle of the kidney. Besides just understanding these words, we're going to see that they actually play a very important role in this actual filtration or this excretion of waste and this ability to not dump too much water or excrete too much water when we're trying to filter out our blood. So I've said before, and you might have heard it already from other lectures or from other teachers, that the functional unit of the kidney is the nephron. And the reason why it's called a functional unit-- I'll put it in quotes-- is because that's the level at which these two things are happening. The two major functions of the kidney: the waste excretion and the maintenance of the water level in our blood system. So just to get an idea of how a nephron fits in within this picture of a kidney-- I got this picture from Wikipedia. The artist tried to draw a couple of nephrons over here. So a nephron will look something like this, and it dips down into the medulla, and then it goes back into the cortex, and then it dumps into collecting ducts, and essentially the fluid will end up in the ureters right here and end up in our urinary bladder that we can later excrete when we find a suitable time. But that's about-- I guess you can imagine the length of a nephron. This is where it starts and then it dips down again. So multiple nephrons are going to keep doing that, but they're super thin. These tubes or these tubules, maybe I should say, are super thin. Your average kidney will contain on the order of one million nephrons. You can't really say, my nephrons are microscopic. They kind of have a-- at least their length when they dip down, you can say, I can see that distance. You can still jam a lot of them inside of one kidney. With that said, let's actually figure out how a nephron filters the blood and actually makes sure that not too much water or not too much of the good stuff in our blood ends up the urine. So let me draw here a nephron. So I'm going to start like this. We'll start with the blood flow. So the blood's going to come in an arterial-- that's an arterial capillary, you could say. So it's going to come in like that. This is actually called the afferent arterial. You don't have to know the names, but you might see that sometime. Blood is coming in. Then it goes into this big windy place. It really winds around like that. This is called the glomerulus. And then it leaves via the efferent arterial. Efferent just means away from the center. Afferent towards, efferent away from the center. And I'll talk about it more in the future, but it's interesting that we're still dealing with an artery at this point. It's still oxygenated blood. Normally, when we leave a capillary system like the glomerulus right there, we're normally dealing with the venous system, but here we're still an arterial system. And it's probably because arterial systems have higher blood pressure, and what we need to do is we need to squeeze fluid and stuff that's dissolved in the fluid out of the blood and in the glomerulus right here. So this glomerulus is very porous and it's surrounded by other cells. This is kind of a cross-section. It's surrounded like that by this structure, and these are cells here so you can imagine these are all cells over here. And, of course, the actual capillaries have cells that line them so there are cells here. So when I draw these lines, these lines are actually made up of little cells. What happens is the blood comes in at really high pressure. This is very porous. These cells out here, they're called podocytes. They're a little bit more selective in what gets filtered out, and essentially about a fifth of the fluid that's coming in ends up going into this space right here that's called the Bowman's space. Well, actually, this whole thing is called the Bowman's capsule. It's a sphere with an opening in here that the capillary can kind of wind around in, and the space right here, this is the Bowman's space. It's the space inside the Bowman's capsule, and the whole thing has cells. All these structures are obviously made-- or maybe not so obviously-- they're made up of cells. And so we end up having filtrate in it. Filtrate is just the stuff that gets squeezed out. We can't call it urine just yet because there's a lot of steps that have to occur for it to earn the name urine. So it's only filtrate right now, and essentially what get squeezed out, I said it's about a fifth of the fluid, and things that are easily dissolved in fluid, so small ions, sodium, maybe some small molecules like glucose, maybe some amino acids. There are tons of stuff in here, but this is just to give an idea. The things that do not get filtered are things like red blood cells or larger molecules, larger proteins. They will not get filtered. It's mainly the micromolecules that'll get filtered, that'll be part of this filtrate that shows up here in the Bowman space. Now, the rest of what the nephron does, the Bowman's capsule is kind of the beginning of the nephron, and just to get an idea of our big picture of our kidney, let's say we're near an arterial. This is a Bowman's capsule right here. It looks something like that, and the whole nephron is going to be convoluted like this. It's going to dip down into the medulla, and then come back, and then it's going to eventually dump into a collecting duct, and I'll talk more about that. So what I've drawn just here, this is a zoomed-in version of that part right there. Now what I want to do is zoom out a little bit because I'm going to run out of space. So let me zoom out. So we had our arterial go in. It gets all bunched in the glomerulus, and then most of the blood leaves, but one-fifth of it gets essentially filtered in to the Bowman's capsule. That's the Bowman's capsule right there. I've just zoomed out a little bit. So we have our filtrate here. Maybe I'll make it a little bit yellow. The filtrate that just comes out at this point, sometimes it's called the glomerular filtrate because it's been filtered by the glomerulus, but it's also been filtered by those podocyte cells on the inside of the Bowman's capsule. But now it's ready to go to the proximal tubule. Let me draw something like this. And obviously, this is not exactly what it looks like, but it gives you the sense. This right here, this is the proximal tubule. And it sounds like a very fancy word, but proximal just means near and tubule, you can imagine, is just a small tube. So it's a small tube that's near the beginning. That's why it's called a proximal tubule. And it has two parts. The whole thing is often called a proximal convoluted tubule. That's because it's all convoluted. The way I've drawn it is all curvy. And I just drew it curvy in two dimensions. It's actually curvy in three dimensions. But the reality is there's a curvy part and then there's a straight part near the end of the proximal tubule. So we'll call this whole thing the proximal tubule. This is the convoluted part. That's the straight part, but we don't have to get too picky. But the whole point of this part of the nephron-- and just to remember where we are, we're now at this point of the nephron right there-- the whole point is to start reabsorbing some of the stuff that is in the filtrate that we don't want to lose. We don't want to lose glucose. That's hard-earned stuff that we ate that was good for energy. We don't want to lose necessarily as much sodium. We've seen in multiple videos that that's a useful ion to have around. We don't want to lose amino acids. Those are useful for building up proteins and other things. So these are things we don't want to lose so we start absorbing them back. I'll do a whole video on exactly how that happens, but it's done actively. Since we're using ATP, and just as a bit of a summary, you're using ATP to actually pump out the sodium and then that actually helps bring in the other things. That's just kind of a tidbit on what's happening. So we're reabsorbing, so just imagine what's happening. You have cells lining the proximal tubule right now. And actually, they have little things that jut out. I'll do a whole video on that because it's actually interesting. So you have cells out here. On the other side of the cells, you have an arterial system, or a capillary system, I should say, actually. So let's say you have a capillary system here that is very close to the cells lining the proximal tubule, and so this stuff actually gets actively pumped, especially the sodium, but all of it, using energy, gets pumped back into the blood selectively, and maybe a little bit of our water. So we're pumping back some sodium, some glucose, and we'll start pumping a little bit of the water back in because we don't want to lose all of that water. If all of the water that was originally in the filtrate we were just leaving in our urine, we'd be excreting gallons and gallons of water every day, which we do not want to do. So that's the whole point. We're starting the absorption process. And then we'll enter the loop of Henle, and actually, this is, in my mind, the most interesting part of the nephron. So we're entering the loop of Henle, and it dips down, and then comes back up. And so most of the length of the nephron is the loop of Henle. And if I go back to this diagram right here, if I'm talking about the loop of Henle, I'm talking about this whole thing right there. And you can see something interesting here. It crosses the border between the cortex, this light brown part, and the renal medulla, this kind of reddish or orange part right there, and it does that for a very good reason. I'm going to draw it here. So let's say this is the dividing line right here. This right here was the cortex. This right here is the medulla. So the whole point-- well, there's two points of the loop of Henle. One point is to make the renal medulla salty, and it does this by actively pumping out salts. So it actively pumps out salts, and it does that in the ascending part of the loop of Henle. So it actively pumps out salts: sodium, potassium, chloride, or chlorine, I should say. Chlorine ions. It actively pumps out these salts right here to make the entire medulla salty, or if we think about it in terms of kind of osmosis, make it hypertonic. You have more solute out here than you have in the filtrate that's going through the tubules. And it uses ATP to do this. All of this stuff requires ATP to actively pump against a concentration gradient. So this is salty and it's salty for a reason. It's not just to take back these salts from the filtrate, although that's part of the reason, but by making this salty, the ascending part is only permeable to these salts and these ions. It's not permeable to water. The descending part of the loop of Henle is only permeable to water. So what's going to happen? If this is all salty because the ascending part is actively pumping out salt, what's going to happen to water as it goes down the descending loop? Well, it's hypertonic out here. Water will naturally want to go and kind of try to make the concentrations balance out. I've done a whole video on that. It doesn't happen by magic. And so the water will-- because this is hypertonic, it's more salty, and this is only permeable to water, the water will leave the membrane on the descending part of the loop of Henle right now. And this is a major part of water reabsorption. I've thought a lot about why don't we use ATP somehow to actively pump water? And the answer there is, there's no easy way to do that. Biological systems are good at using ATP to pump out ions, but it can't actively pump out water. Water's kind of a hard thing for proteins to operate on. So the solution is to make it salty out here by pumping out ions and then water, if you make this porous only to water, water will naturally flow out. So this is a major mechanism of gaining back a lot of the water that gets filtered out up here. And the reason why this is so long is to give time for this water to secrete out, and that's why it dips nice and pretty far down into this salty portion. So then we'll leave the loop of Henle and then we're almost done with the nephron. Then we're in another convoluted tubule, and you might even guess the name of this convoluted tubule. If this was the proximal one, this is the distal one. And actually, just to make my drawing correct, it actually passes very close to the Bowman's capsule, so let me do it in a different color. The distal convoluted tubule actually goes pretty close to the Bowman's capsule. And once again, I've made it all convoluted in two dimensions, but it's actually convoluted in three. And it's not that long, but I just had to get over here and I wanted to get over that point right there. It's called distal. Distal is further away. It's convoluted and it's a tubule. So this right here is the distal convoluted tubule, and here we have more reabsorption: calcium, more sodium reabsorption. We're just reabsorbing more things that we didn't want to lose in the first place. There's a lot of things we could talk about what get reabsorbed, but this is just the overview. And we're also reabsorbing a little bit of more water. But then at the end right here, our filtrate has been processed. A lot of the water's been taken out. It's a lot more concentrated. We've reabsorbed a lot of the salts, electrolytes that we want. We've reabsorbed the glucose and a lot of the amino acids. Everything that we want, we've taken back. We've reabsorbed. And so this is mainly waste products and water that we don't need anymore and then this gets dumped into collecting ducts. And you can kind of view this as the trash chute of the kidney, where multiple nephrons are going to dump into this. So that might be the distal tubule of another nephron right here and this is a collecting duct, which is just a tube that's collecting all the byproducts of the nephrons. And the interesting thing is that the collecting duct further goes into the medulla again. It goes into the medulla again to the salty part again. So if we're talking about the collecting duct, maybe the collecting duct's coming back into the medulla, collecting all of the filtrate from the different nephrons. And because it goes back through that super salty spot in the medulla, we actually have four hormones called anti-diarrhetic hormone that can dictate how porous this collecting tube is, and if it makes it very porous, it allows more water to leave as we go to the medulla, because this is very salty, so the water will leave if this is porous. And when we do that, what that does is it makes the filtrate-- and we can maybe start calling it urine now-- even more concentrated so we lose even less water, and it keeps collecting, collecting, collecting until we end up here, and it leaves the kidney and goes via our ureters to the urinary bladder. So hopefully, you found that helpful. I think the neatest thing here is just how we actively reabsorb the water and how we-- well, actually, in my mind, that is the neatest part in the loop of Henle.