 I want to show you how this concentration gradient is established. And I'm talking about why at the base of the descending loop of Henle, why the interstitial concentration is 1,200 milliosimals, like that's crazy talk. And it's a combination of the work of the ascending loop and the commonly pumping solutes out and something we haven't talked about yet, which is the capillaries and the setup of the capillaries which basically pick up the fluid, the extra fluid and the extra solutes as necessary and take them back into the bled stream. So watch this amazing process. Do you accept that this is my initial state? The filtrate that came out of my glomerulus, the filtrate is isosmotic to the blood, so it's at 300 milliosimals. And the concentration of the interstitial fluid, if we didn't do anything, would be 300 milliosimals. Like that's just normal osmolarity anywhere you go. Please notice this is proximal convoluted tubule, which means what is this descending loop of Henle? Which means what is this ascending loop of Henle? Which means what is this distal convoluted tubule? This is drawn differently. It's drawn differently just to clarify. We don't need to show the juxtapglomerular apparatuses. We don't need to do any of that stuff. What I want you to do is imagine the scenario before the concentration gradient is established. So here we are. And this fluid, we're going to follow this fluid, this chunk of fluid that's in the proximal convoluted tubule. We know we're just reabsorbing stuff, normally solutes and water, so we're going to stay isosmotic. So if we move forward, here's the scoop. You have transporters in the ascending loop of Henle that pump solutes out and they have a rule that they must follow. They can only pump solute out, no matter how much ATP is available, they can only pump solute out to a difference of 200 milliosimals. So if they pump solutes out, what's going to happen to the concentration inside? They're getting rid of solutes. This concentration should go down. What's going to happen to the concentration outside as solutes are pumped out? The concentration should go up. So let's see if that is indeed what happens. Look, it does happen. Can we keep going? No, because we can only have a difference of 200 milliosimals. If you have more than that, a bigger difference, you're going to have too much leakiness, you can't maintain that. Watch what happens next. I believe we're going to move the whole thing. No, we're going to get all these guys to establish their difference of 200. Did you see that? So now I just increased the concentration of the interstitial fluid just by pumping out, but also decreased the concentration of the filtrate. Now, let's keep going in response. What's going to happen in the one place where water can leave? Water is going to leave. Water is going to move down its... Water is going to move by osmosis to from the filtrate into the interstitial fluid. Now, here's what I'm going to tell you. In the next section, we're going to look at the blood system that picks up the water. So you can accept that the water isn't going to dilute the concentration that we're establishing here. The water is going to be picked up by the capillaries, and I'll show you why that is. So here it comes, it's coming out. What's going to happen to the concentration in here as water leaves? The concentration is absolutely going to go up to the water left, so it becomes more concentrated. Are you cool? Let's move the filtrate. So the filtrate, all of this, is going to move. So this 200 is going to move up here, this one's going to move up. This 200 is going to move up and replace this. It's not an actual visual, which is unfortunate, so I can't animate this thing. But here we go. Did you see my filtrate move down? This used to be 400, but now it's 300. This used to be 300, but now it's 200. Here we have our difference already established, 200. We can't do more than that. Can't do more than that. Here we can pump solutes out, so let's do it. We're going to pump the solutes out here. What's that going to do to the concentration? Dude, we can have a difference of 200, so let's pump them out until we get a difference of 200. Now look, my concentration just got crazier. In response, what's going to happen here? We don't have water that's going to come out. We don't have water coming out here because it's isosmotic. Does that work? But here we have it's hyperosmotic in the interstitial fluid, so water is going to come out of the filtrate. That's going to make the whole thing more concentrated, and we can just keep it going. We can move everything down. Look, we moved. Now, since everything moved, look, here we're equal. This, we can pump a little bit out. This has the difference of 200, so we're not going to pump out, so let's see what happens. Indeed, we're pumping out solutes. That's going to decrease the concentration inside and increase the concentration outside. Right? And look, there it is. We've established our 200 difference. Now, this is isosmotic, so water's not going to move. Water will move here, though, and then water will definitely move here and here. So let's see what that happens. See how the water is moving out. Water is being picked up by the bloodstream, and this is how we establish the interstitial concentration gradient. And the bloodstream, the blood supply, is going to come in and take out the water and some of the solutes so that we can maintain this. I could keep going for forever. We just moved the whole thing down, and I could keep going around and around and around until we get to that place where we've established 1200 milliosmoles down here. I don't have to. Maybe I can do it one more time to show you. Dude, let's establish a 200 difference. Once we've established our 200 difference, let's get the water that's inevitably going to come out. As the water comes out, the whole thing's going to get more concentrated until it reaches its isosmotic with the interstitial fluid. Water gets picked up by the bloodstream. Now the whole thing moves again. We continue and continue and continue until we have the concentration gradient established. That's why it doesn't get washed away. And when we talk in the next lecture about how we make concentrated urine and regulate the various substances that we're going to find in our urine, you will appreciate that, okay, yeah, you can accept that this does exist. Now I want to show you why we don't suck all the water and the solutes out of this gradient with our bloodstream, blood supply, the vasorecta.