17. Renal Physiology - Cont.

Professor Mark Saltzman: So, I'm going to continue talking about renal physiology today; again, this is covered in Chapter 9. You will have noticed as you're reading Chapter 9 that there's more covered than just renal physiology there. It also talks about biotransformations and the role of the liver in getting rid of substances. We're not going to cover that part in class but I encourage you to read it as a whole to get a broader perspective of how kidney function fits into the overall ability of your body to maintain what we call homeostasis or a constant environment. As I talked about last time, one of the important elements of this constant environment is to maintain sodium, potassium, bicarbonate, and the levels of other key molecules at a constant level throughout the day and throughout your life. It does that--and you're able to do that not by regulating how much you eat of those things, but they kidney does that for you by sensing what concentrations are in your body, keeping what you need and getting rid of what you don't need. We started talking about how the kidney is able to accomplish this remarkable task. Hopefully, the main point I wanted to make in the last lecture was how grateful you ought to be that your kidneys do function properly, because as one of the results of that is that you only have to produce about 1 L or 1.5 L of urine per day to get rid of all the waste products that are produced by metabolism in your body. Without that concentrating ability of your kidney, I mean the ability of the kidney to produce a urine that's very concentrated in waste rather than dilute in waste, you only have to relief yourselves of 1.5 L of fluid everyday instead of the 100 or so liters that you'd have to in the absence of that ability to concentrate. That makes possible a lot of the things that we enjoy in life like sitting through a 50 minute lecture. What I want to talk about today is some of how the kidney does that and I'm going to go back a few steps because I covered a lot. I wanted to give you an overview at the end of sort of the last half of the lecture last time, about how the nephron functions and I'm going to go back now and step through it a little bit more slowly and talk about some of the details. Now, the--like the other systems we've talked about the brain, the heart, the circulatory system, the kidney has a very sort of rich and complex physiology which now we understand fairly well. We're only going to scratch the surface of that and if you get excited about it, there are ways for you to learn more in your time here at Yale and certainly beyond. This is a picture that I showed you before, sort of to orient you again; I have this picture of a kidney lying on its side. It's a layered structure, the outer layer or the sort of shell around the outside of the kidney, this fibrous capsule which sort of distinguishes what's inside the kidney from what's outside the kidney, the layer below that is called the cortex, the inner layers that have these sort of striations is called the medulla. All of this comes together in this region here called the renal pelvis, this region where the renal artery enters, the renal vein leaves, and the ureter exits the kidney as well. Everything collects sort of at--what's at the bottom of this diagram but it would be on the inside or medial surface of the kidney and it's in its anatomic position. I mentioned last time that the functional units of the kidney are this structure called a nephron. Each kidney has about a million of these nephrons and that they're oriented within these layers, so a nephron is going to sit sort of this axis here, going up and down in this diagram. That's the reason why I turned this kidney on its side so when you look at the nephron here you can think about it sitting in this orientation in the kidney. Of course, the kidney has this sort of curved structure so the nephrons are going to sort of radiate out from the central portion through the medulla and up into the cortex, with the glomerulus near the cortex, and the Loop of Henle stretching down into the medulla. I also mentioned several features of the nephron. One is the glomerulus where the place where filtration takes place, this tuft of capillaries that's surrounded by a capsule. The capsule is there to catch this filtrate that's produced by high pressure inside the arteriole system forcing some fluid out through these leaky capillaries. The capsule, called Bowman's capsule, is there to catch this fluid and start it on its way through this series of tubules. I talked about different regions of the tubules, the proximal convoluted tubule, proximal because it's near the glomerulus, the Loop of Henle, this structure that stretches down through the cortex into the medulla and then back up again, and the distal convoluted tubule which is farther from the glomerulus and empties into the collecting duct which then moves down through the cortex, through the medulla, and into this region of the renal pelvis where all the collecting ducts empty into the ureter and then onto the bladder. A filtrate of plasma is produced here in the glomerulus and as this filtrate of plasma, this fluid that is going to be urine at some point, moves through this series of tubules, it gets processed, it gets modified, it gets changed. In particular, the cells of these tubules are able to reabsorb the molecules that you need. They reabsorb a lot of water, they reabsorb a lot of sodium, potassium, bicarbonate, and they do that without reabsorbing a lot of the waste products you don't need like urea; as you might guess given this configuration that there's some interplay between the activities that happen at different parts of the tubule. That is, if sodium is being reabsorbed in the proximal tubule, which it is, then where does that sodium go? It's pumped out of the tubule and into the space around--into the space of the kidney surrounding it and so sodium is going to accumulate out here. Now, where does that sodium go? Well, eventually it's going to back into the blood so there must be a lot of blood vessels around there as well. They're not shown in this diagram; they'll be shown in the next one. This sodium leaves the urine through the walls of the tubules and is reabsorbed back into blood vessels. That leaves some sodium out here in this space, and one of the really interesting things about the kidney, which we won't be--about the nephron, in particular, that we won't be able to talk about in so much detail, is how one part of its tubule system uses the result of the other in order to establish gradients to produce this concentrated urine. We're not really going to talk about that but I wanted to mention it on this diagram here, that there are real important reasons why the tubules are arranged in the anatomical pattern that they are. An additional thing, which I mentioned last time, is that if you looked, as cell biologists did, at the cells that make up these linings of these tubules, you'd find that they look different in different parts of the nephron. This has to do with their different functions. Some are very good at reabsorbing sodium, some are very good at reabsorbing water, and some are good at other functions. The function of each--of these groups of cells that make up different portions of the tubule is critical for overall nephron function. I'll say a little bit about that just to give you a flavor for how that happens without talking too much about the details. This shows a collection of nephrons, sort of in a more complex arrangement. I've got the kidney here so you can be reminded again that this might be a structure that comes from here and then you can see several nephrons. In particular, there's a lot of glomeruli in this picture where the nephron that's associated with this glomerulus and this glomerulus aren't shown so that we can focus on just a few of them. Just to give you a sense for these million nephrons that are arranged in the kidney, they have their glomeruli at different locations, up and down, they are surrounded by their proximal and distal convoluted tubules, and these Loops of Henle stretch down into the medullary region and then come back up. I wanted to use this more complicated diagram to sort of illustrate the flow. How does fluid move through this--through one particular nephron within this system here, and so I hope this comes out. Did you see the red arrow up here? That red arrow represents arteriole flow of blood and this is a branch of the renal artery which is serving this whole collection of nephrons that are here. Of course that vessel branches, at some point, and here I show a branch of a branch, which is heading up towards these glomeruli up in this upper region of the cortex. Blood is flowing through these branches of the renal artery into the substance of the kidney and it flows up into a glomerulus here. Now, because this is not too distant a branch from the aorta pressure is still high here. You know that pressure remains pretty high until you get down to the arteriole levels; we learned that when we talked about the circulatory system. The pressure here is fairly high, it might be 70 or 80 millimeters of mercury. This is the pressure that drives filtration in the glomerulus. The green arrow, which just appeared up here, is supposed to indicate for this glomerulus right there filtration happens. Because of the pressure drop in the glomerulus, the low pressure in Bowman's space, this space that surrounds it, fluid is driven through the walls of the capillary and collected outside. What is produced there is really, what I called last time, an ultra-filtrate of plasma. That is the urine or the filtrate that's going to become urine, at this point, would be identical to plasma in composition except all of the big items are removed; all the large molecules, all the cells are removed, other than that it's identical. The concentration of sodium in the filtrate is the same as the concentration of sodium in the plasma, concentration of urea same as concentration of the plasma, concentration of bicarbonate and so on. As long as any molecule that's below that cut off it's going to have the same concentration as it is in plasma, so there this green arrow represents filtration. From there the fluid moves through the distal convoluted tubules, which you can't really see here, but it's up in this portion. The white, if you can see on the--here some of these are white and some of them are blue. The white ones are the proximal convoluted tubule but they're really not like in the diagram before, these convoluted tubule are sort of mixed together, they interact with one another. This filtrate goes through the proximal convoluted tubule down in the Loop of Henle and now you can see--follow these green arrows, it's moving down, it takes a turn deep in the medulla and starts coming back up again and heads back up to the distal convoluted tubule. Now, we're not going to talk about it at all in this class, but if you go on to study physiology, one of the most amazing things about the nephron is its--is that this loop allows the nephron to create a gradient of osmolarity within the tissue outside the nephrons in the kidney. It's able to create a concentration gradient of sodium basically, but of ions that it can then use to reabsorb water. Austin, who was sitting in the front last time, mentioned that she thought osmosis was an important part of how the kidney works and it is. Osmotic forces are how water concentration--how water moves around in the kidney. The kidney is able to regulate how concentrated or how dilute your urine is by using osmotic gradients and those osmotic gradients are established in the Loop of Henle. It's really a remarkable sort of biophysical process that you'll learn about if you study more renal physiology. There's a reason why the fluid goes down and goes up and it's to establish these gradients which the kidney uses to concentrate or extract water from the urine. This orange area here represents the flow going from the distal convoluted tubule back into the collecting duct and down through the collecting duct and eventually into the ureter. This is just a more complicated diagram of what I've told you already and it's--I encourage you to sort of walk through it and look at all the parts so you have a sense for how the anatomy of the kidney works. This picture I showed you before, just to remind you of the first step in producing urine, is filtration. I've talked about it several times now but there's this tuft of capillaries which sits inside this capsule called Bowman's capsule. There's an artery which feeds blood in, called the afferent arteriole. 'Afferent' means towards so it's the arteriole that's carrying blood towards the glomerulus, and the efferent arteriole which carries the blood out of the glomerulus. Now, the flow rates here would be different; the blood that's flowing through the--the amount of blood flowing through the afferent arteriole and the amount flowing through the efferent arteriole, 'efferent' meaning away from, are different because some fluid is lost. That's the amount that's filtered into Bowman's space. We talked about last time that these are both arterioles and that because they're arterioles they can constrict or reduce their diameters and expand, dilate or expand their diameters. Because of this, if it constricts then the pressure drop over that length of arteriole is going to change. Having these two adjustable resistances on both sides of the glomerulus allows each nephron to regulate what the pressure is in the fluid inside the capillaries of the glomerulus. Now, since its pressure inside these capillaries which is the driving force for filtration, that means that each nephron has the ability to adjust how much is filtered in each glomerulus. Now, if--we're going to--in a slide or two going to talk about a concept called the glomerular filtration rate. This is a concept that's defined for your whole kidneys and the glomerular filtration rate, we all have a glomerular filtration rate, it's the rate at which filtrate is being produced in all the glomeruli of our kidneys. It's the rate at which the fluid that's going to become urine is produced. It's an important measure of how well your kidney is functioning, is how much filtrate it's producing per minute. What I want to emphasize on this diagram here that another remarkable thing about the function of the kidney is that each of these individual million or two million nephrons are able to adjust their individual filtration rate by changing the pressure within the glomerulus. Of course this was a picture I showed you last time of the actual filtration membrane, the surface of these capillaries where this pressure drop acts and through which large things are filtered out. Here's a cartoon of the glomerulus and this cartoon actually shows several things. One it shows the arteriole, the afferent arteriole that's coming in and the afferent arteriole that's going out and so here's the tuft of capillaries that make up the glomerulus. Here's Bowman's space, which is ready to catch the filtrate. This first arrow here represents the filtrate that's produced in the glomerulus of this particular nephron. Now, after that filtrate's produced it starts to flow through the proximal convoluted tubule and then through the Loop of Henle, and the distal convoluted tubule, and eventually the collecting duct, and as we know from last time, several things can happen. One is that molecules within this fluid can be reabsorbed, and if they're reabsorbed they move out of the tubular system and into--back into blood. That's why there are blood vessels surrounding all the nephrons in the kidneys, so that there's a blood flow that's ready to catch these molecules as they're reabsorbed from the tubules. We also mentioned that there are some special processes of secretion so that the blood vessels in the kidney are smart enough to detect some molecules and secrete them actively into the urine. Then, whatever is not reabsorbed, plus what's secreted, is what ends up in the urine after it flows through all the tubules. What's different here is then instead of showing the complex geometry of the tubules, this just shows a tube which is going to the bladder down here. This diagram is simplified because I wanted to just talk about one concept and that's this glomerular filtration rate, the rate at which fluid is produced in the glomeruli of all of the kidneys. The question is how would you measure this glomerular filtration rate in people? If it's an important measure of kidney function how would you measure it? It turns out that physiologists have learned how to measure it by taking advantage of a particular molecule called inulin. Inulin is a molecule that's not a normal part of our diet, it's a polysaccharide, but it's a polysaccharide that is of sort of intermediate molecular weight. I think it's about 1,000 or 2,000 in molecular weight, but your body doesn't know how to digest it. If you get inulin in your blood, it just circulates and isn't changed at all, but it's small enough that it's filtered in the glomerulus. If there's inulin in the blood then it gets filtered through the glomerulus and ends up in the ultra-filtrate. Another remarkable property about inulin is that it's not reabsorbed. There's no reason for your body to reabsorb it because it's not something you can really use and you don't need it, and it's not actively secreted, so whatever gets filtered ends up in the urine. This molecule turns out to be a convenient tool that physicians can use to measure your glomerular filtrate rate in the event that they want to test your kidney function. How would you do that? You would inject an amount of inulin into the blood and you would measure how much--what's the concentration of inulin in the plasma? You would inject some amount of inulin and you'd measure how much of it is in the plasma. You'd then wait over some period of time and you would collect the urine and you'd measure how much of that inulin appears in the urine. Now, since inulin is neither reabsorbed nor secreted, however many molecules of inulin are filtered at the glomerulus has to be the same as the number of molecules that enter the urine. It's not reabsorbed, it's not secreted, so whatever number of molecules enter here they have to leave here. So, if I know the concentration of inulin in the urine I know how much urine is produced over some period of time, I know the concentration in the plasma. Remember that one of the features of this ultra-filtrate is that it just cuts off in molecular weight but whatever concentration--if you're below that molecular weight, whatever concentration is in the plasma is the same as the initial concentration in the ultra-filtrate, and so the plasma inulin concentration is the same here. If I just do a simple accounting for all the inulin, whatever the glomerular filtration rate is times the concentration in the plasma has to equal whatever the concentration in the urine is times the rate of urine production. I can measure in a person how much urine they're producing per time, you can measure the concentration of inulin in the urine, you can measure the concentration in the blood and so you can calculate the glomerular filtration rate. This is a method that takes advantage of the unique properties of this molecule inulin. This is a--physician's use this general strategy in a variety of ways to measure flow rates of things inside your body that are difficult to measure directly and they do that by looking at what's called a tracer molecule. In this case, insulin is a tracer. It's picked for its particular properties, that it's filtered freely in the glomerulus but neither reabsorbed nor secreted. It allows you to calculate some physiological function sort of deep inside your body, so you can measure glomerular filtration rate this way. I've already showed you this picture that shows the vascular system of the kidney, sort of laid out in a line here. Here's the renal artery branching into afferent arterioles, branching into glomerular capillaries, back into efferent arterioles and then to the capillaries that surround the tubules, and the pressure drops that are associated with that. I show it just to remind you of how the kidney could regulate its glomerular filtration rate by changing the diameters of either the efferent or afferent arteriole. Changing the resistances, changing the relative pressure drops along the kidney vasculature, and therefore regulating the important level which is here how much pressure is in the glomerulus to drive filtration. I've talked about this several times now, and I think if you study the diagram and read the text hopefully that will make sense to you. It is--this pressure is what drives inside the glomerulus the flow of filtrate and the production of filtrate that becomes urine. What happens after this point? What happens are these two processes that we've talked about that make the kidney different from a simple filter. Filtration is an important part of its function, that's easy to understand from sort of an engineering perspective. You produce this ultra-filtrate, and then the kidney works very hard to recover the molecules that you need so that you don't have to produce a large volume of urine in order to get rid of the waste. It does that by two processes, reabsorption and secretion, which I've already mentioned, and we're really going to focus mainly on reabsorption for the rest of the time here today. In reabsorption the key elements of reabsorption are reabsorption of water or return of much of this volume of water that's filtered at the glomerulus and recovery of solutes that are needed like sodium and potassium and bicarbonate. This table just sort of tells you in general what happens at different portions of the nephron. Filtration happens in Bowman's capsule, I think I've said enough about that one. Selective reabsorption happens in all other elements of the tubules, the proximal, the Loop of Henle, and the distal convoluted tubule. How does selective reabsorption happen? It happens by the physical processes of diffusion or just the movement of molecules down concentration gradients, and it also happens by active transport. We talked about active transport earlier. We talked--for example when we were talking about the action potential, we talked about this active transport system that's able to shuttle sodium and potassium molecules across membranes. So, most cells in the body have this active transport system called the sodium potassium pump, or the sodium potassium ATPase. Its main function is to bring sodium from inside the cell, pump it out, take potassium from outside the cell and pump it in. As a result of the action of this pump that's what creates this normal state that you have high extracellular sodium concentrations and high intracellular potassium concentrations. If that pump wasn't working, then sodium would diffuse from outside to in because the concentration is higher outside than inside, and potassium would diffuse from inside to out because the concentration is higher inside than outside. Now, this pump is driven by ATP. ATP is a molecule, it's one of the end--it's a molecule that's produced when we metabolize sugars and get energy from them. We store them in the form of ATP, and then the body uses ATP to do things like operate this pump. A lot of the ATP that you're using right now in your body is being used to maintain the concentration of sodium high outside your cells and potassium high inside your cells. Why are you spending so much energy doing that? Why would your body spend so much energy trying to maintain these differences of ion concentrations? Student: [inaudible]Professor Mark Saltzman: Because these concentrations have to exist for cellular functions like--? Like the generation of action potentials in the nervous system, like the generation of action potentials in the heart that drive contraction and beating of the heart. Without these differences of concentration you could neither send nerve impulses, your heart would not beat; maintains life and lots of the activities of life and so a lot of energy goes into producing them. In those same kinds of processes are used in the kidney to shuttle ions from one place to another, I'll show you an example of that in a minute. Reabsorption of water, I tried to emphasize last time how important reabsorption of water is, because you have to produce a lot of filtrate in order to collect a lot of waste products. You got to produce a lot of filtrate in order to get a lot of urea into the urine. You don't want to lose that much water because any water you lose you have to drink to recover from. Reabsorption of water is a very important process that happens in the kidney, it happens in all the tubular segments. Secretion happens mainly in the distal convoluted tubule, and as I mentioned, we're not going to say very much about that. If we were just able to look and take one nephron and take that complicated series of tubes that I showed you in diagrams before and stretch it out while it still is functioning, and then measure as a function of distance along this complicated tubule, what's the concentration or relative concentration of some of these key molecules we're talking about? What we would see is shown in this diagram here. Now, I mention this special property in inulin, that it's neither reabsorbed or secreted, and that's shown here by this flat line, so whatever gets filtered in the glomerulus, at the glomerulus, that number of molecules remains in the urine throughout its progress through the tubules. That's why you can use it as a tracer to measure GFR (glomerula filtration rate) because it's neither reabsorbed in any of these tubules nor secreted, so the number of molecules that come out in the filtrate, that's the number that leave in the urine. That's not true for glucose. I mentioned yesterday that glucose is not normally found in urine. When you do find glucose in the urine of an individual that indicates that there's some disease process going on and that's because glucose is very efficiently reabsorbed in the proximal tubule. If I just looked at concentration within the filtrate, within the urine through the proximal tubule, there'd be a lot of glucose here and that concentration drops as we move through the proximal tubule such that there's no glucose in the filtrate by the time we get to the end of the proximal tubule. That's one of the simpler cases, that glucose is just reabsorbed in the proximal tubule. Sodium, on the other hand, has a much more complicated pattern. That sodium concentration drops as you move through the proximal tubule so a lot of that sodium is reabsorbed, about two-thirds of it is reabsorbed in the proximal tubule. Then, if I looked over the Loop of Henle in the descending loop, the loop that goes down, actually sodium molecules come back in, and then sodium molecules go back out in the ascending loop. This has to do with the establishment of gradients of sodium that I mentioned before in the interstitial space which allows the kidney to--this represents those--the sodium that's used to create those gradients, those gradients are used for water absorption. Then, most of the rest of the kidney is--the rest of the sodium is cleaned up or recovered in the distal tubule and the collecting tubules. Urea, which has this pattern here, a lot reabsorbed but then it comes back out again, and then it's reabsorbed finally. Now, some of these things are going to be hard for you to understand why they go in and out. It has to do with this complex interplay that I mentioned before between processes that are happening in different parts of the tubule, establishing gradients that are then used in different portions to aid in reabsorption. How do these things happen? How is sodium, for example, reabsorbed so efficiently in the proximal tubule? Well, I'm going to give you a simple example of that just so that you have a way of thinking about the mechanism, but you're going to remember that there's more going on than just what I described. Imagine that this is the proximal tubule, so a part of the tubule just after Bowman's space, where sodium concentration is high inside the filtrate. What's the concentration of sodium in the filtrate right after the glomerulus? It's the same as the concentration in plasma. What's the concentration of sodium inside cells that line the tubule? Well, like all cells these have sodium potassium pumps and so the concentration of sodium inside these cells is low. The intracellular concentration of sodium is low. High concentration here, low concentration here, so if this membrane is permeable to sodium it's going to diffuse from inside to outside. What would allow--does sodium diffuse through membranes? Charged molecules don't diffuse through membranes on their own, not if it's just a lipid bilayer. What allows sodium to diffuse? What kinds of structures allow sodium to diffuse through a lipid membrane? Protein channels, ion channels, sodium channels--so there must be sodium channels in these membranes and there are, and the sodium moves through. Now, you have high sodium inside or higher than before because sodium can leak through these channels, but you have on this other surface of the cell, you have a lot of these sodium potassium pumps. These sodium potassium pumps are constantly pumping sodium out and bringing potassium, sodium out, potassium in and there's pumps here, there's pumps here, there's pumps here. So, any molecules of sodium that enter this side get efficiently pumped out through the other side. The net effect of these two processes, diffusion on this boundary and active transport on this boundary, is that sodium molecules move from inside the tube to outside the tube. Now, if sodium concentration is high here where is it going to go? Well, there are blood vessels up here and they're going to reabsorb this sodium just by simple diffusion processes as well, so blood that's flowing through this region is going to take all the extra sodium away. The net effect here is that sodium gets moved from--in this filtrate, this urine back into the blood. Now, the property of these cells, which allows this to happen, is that the sodium potassium pumps are only on this surface, they're not on this surface. The sodium potassium pumps are only on this surface and not on this surface. On this surface just diffusion of sodium down its gradient is the only thing that happens, and on this surface that sodium is moved out into the interstitial space. This is one example of the kind of properties that cells of the tubules use in order to selectively move a particular molecule from one side to the other. What are the properties that we talked about? Membranes are leaky, membranes are leaky because they have channels, here's a leaky membrane here, and membranes have active transport systems that move selectively ions from one side to the other. This is an example that shows how that works with sodium, there are systems that work with all of the ions that we've talked about, not in exactly the same way but with the same sorts of concepts. I don't want to say too much about this diagram. I just show it here so that you can look at it at your leisure if that's what you would do with your leisure time. You could study this diagram which just shows you something about what kinds of transporters are functioning in different cells of the proximal tubule, the ascending or descending limb of Henle's Loop, the distal convoluted tubule, the collecting duct. These are channels that allow for selective movement of certain kinds of molecules like sodium, like glucose, like bicarbonate and potassium. This table is a little bit more complicated than the one I showed you before, but just to try to put it all into perspective again, that the kidney because of glomerular filtration produces per 24 hours 26, 000 milliequivalents of sodium are filtered and almost all of those are reabsorbed, only a few of them are excreted. Now, if you happen to eat a lot more salt on one day, what would happen? You would filter more, you would reabsorb a little less, and you would excrete that balance. You would filter more because you would have eaten more salt then you needed so more sodium would appear in your blood than normal. The concentration would be slightly higher in the plasma, you'd filter more of it, you'd reabsorb less of it, and the result would be you would excrete more. The same thing with potassium and with these other molecules here, and interestingly, what this shows is the percentage of these molecules that are reabsorbed. Then, in this table here shows you what part of the tubular system that reabsorption takes place, so you could think about that if you wanted. I want to just say one last word about water balance and this is just to illustrate the concept of homeostasis that we've been talking about for all these ions before, that you could think of your body as a vessel where there are inputs and output. For water the input is mainly the water that you drink or that you've taken in food because some foods contain high quantities of water too. For a normal individual you're going to take about 2.1 L of water in per day in food and drink. You synthesize some water because some of the chemical reactions that occur during metabolism have water as a byproduct, so you synthesize some water. Your overall daily intake is about 2.3 L of water per day. You have to get rid of that water, because if you're taking in water and you're not getting rid of it then you're expanding your volume. You get rid of it in a variety of ways, about a liter and a half in urine, almost a third of a liter through your lungs because you breathe in air that's relatively dry, you breathe out air that's very humid. If you take a glass plate and you breathe out on it, it gets foggy, you could see water condense because your breathe is much more--has much more water in it than the air around us, so we lose actually quite a lot of water that way. Through sweat and other activities you lose more water, so that your daily loss balances your daily intake. Now, what if you drink more water? What if you drink--what if you're--I know there's a lot of water bottles in the room here. A lot of you carry water around with you and you drink water constantly throughout the day, what happens? You drink more water than this, if you ingest 3.1 L per water then you've got to lose 3.1--you've got to lose 3.3 L of water. Normally what you lose in your lungs and by sweat and other mechanisms doesn't change, what changes is the amount that you use in urine. You're all familiar with this, if you drink more water one day than you did the day before, you're going to produce more urine, go to the bathroom more often. I don't know another way to say it--well, I do know. I don't want to say it any other way. What if you--what if instead of water you decided on another day not to eat any salt? You're not going to eat any salt during the day what would happen? Well, you would need to maintain your salt concentration high, need to maintain the salt concentration high. Your kidney has to lose a little bit of salt, it can't recover 100% so if you ate no salt at all, you can't recover 100% of it you're going to lose a little bit of the salt through your urine. It can't recover 100% of the salt, so you're going to lose a little bit of salt through your urine. If you didn't eat any salt then your sodium concentration is going to drop, it would want to drop. Your body won't allow that to happen, the kidneys won't allow that to happen. If it notices that you're sodium concentration is going down but you're not bringing any more sodium in, how else can it change the concentration? It could decrease the volume of water in your body so it could produce more watery urine, or urine with more water in it. Try this experiment, don't eat any salt, it means you probably can't go to the dining hall but if you don't eat any salt for a day you will notice that you're producing more urine. If you weight yourself in the morning and you weigh yourself at night, your weight will go down over the course of one day. That's why it's easy to lose a pound or two, you can do that by just restricting salt in your diet. It's a nice example of how your body--how the kidney in particular senses what concentrations are present in your body and adjusts what it can depending on what you're eating in order to maintain what's important. What's important is the concentration of extracellular sodium has to be at the right level so that your brain and your heart can function properly. Okay, that's it for renal physiology, in the section this afternoon we'll talk about dialysis. Dialysis is the technology developed by biomedical engineers over the last century that allows people to live without normal kidney function by performing some of these essential functions outside the body.