Welcome back. So, today we want to talk about the renal system, and we're, this is going to be the third of our lectures about the renal system. And the things that we want to discuss today, are, is, how the kidney then, is uses the tubular, the tubular transporters to reabsorb materials that is to take it from the filtrate back into the body or into the blood. And also to secrete materials bypassing the filtration route that we talked about the last 2 times. So, the specific learning objectives are first that we're going to explain the importance of the peritubular capillary in the kidney cortex. The secondly, we want to describe the cellular mechanism for transport of materials from the tubule to the interior of the tubule, that is within the lumen, across the cells and into the blood. And and we're going to use the glucose transport as our, as our example. And then very briefly, we'll talk about moving bicarbonate across this, this system. Third, we want to talk about transcellular transport, that is the movement across cells versus movement between cells, the paracellular pathways. And this is the way that water, then, will move across this particular region of the kidney. And and we'll also talk very briefly about the solvent drag of potassium. Fourth, we will define the maximal transport rate and the transport threshold for, for items that are using transporters. And five, we'll dis, we'll consider secretion. And secretion only very, very brief briefly and then also we'll talk about secretion, in particularly secretion of potassium, and again very briefly. So let's, let's revisit then our tubule and that's what's drawn here. So we have the afferent arteriole, which is feeding into the glomerulus, and that's our first capillary bed. And that first capillary bed is drained by a second arteriole, and that's the efferent arteriole. And the blood then drains into a, into the, the second capillary bed, which is called the peritubular capillary. And the peritubular capillary runs along the to, the renal tubule within, within the the the kidney. We also have the, you know, tubule, and that's what's diagrammed here. And around circling, around the glomerulus, we have Bowman's capsule, and that's this. And then from Bowman's capsule, we enter into the rest of the renal tubule. And this is, the first region is the proximal convoluted tubule. And then we'll go through the loops of Henle and eventually lead to the distal tubules and, and the collecting duct and then out through the, the ureter. So the process is, that we're talking about is the beginning between the glomerulus and the in Bowman's capsule we have this filtration. And the filtration will move solutes and water into the lumen of the renal tubule. And we know that that's going to be governed by specific pressures, and that's going to be hydrostatic pressure minus the oncotic pressures. So now we want to move materials from the renal tubule back into the blood. And this is going to be very important, because within 24 minutes, we can completely exhaust the cardiovascular system if we do not bring the fluids the water in particular back into the, into blood. We also need to be balancing ions and that is, in particularly with bicarbonate, if we are filtering bicarbonate freely across the glomerulus and we need to move that bicarbonate back into the blood to use it as a, for ph buffer. And so reabsorption then, which is what we'll talk about predominantly today, is how we're moving solutes from the lumen of the tubule back across the cells back into the, in to the blood. And then, there's also a way, that we can bypass filtration, and move materials directly from the blood, from that peritubular capillary, directly into the renal tubule, and that's called secretion. So what are the things that are governing this particular region? So the most of the movement then, the reabsorption, filtration an, and reabsorption is going to be governed by pressures. And that's what's diagrammed here. So you recall, we had this portal system where we have the afferent arteriole, which is on one side of the glomerulus the first capillary bed and then we have the efferent arterial which is on the second side of the capillary bed. And that's different from what we see in normal places within the body. Where we have an arterial feeding into a capillary which is then feeding into a venule. Within the, within the nephron bend, this afferent arteriole and the efferent arteriole, their diameter of the lumens of those, of those vessels are regulated independently. And we can maintain the hydrostatic pressures within the glomerulus such that it always exceeds the oncotic pressure. And when hydrostatic pressure is higher than the oncotic pressure and it's higher also to the to Bowman's capsule, the resisting pressure of moving fluid into Bowman's capsule then we have filtration. And across this region of the nephron, there is always, always, always filtration. When we move into the peritubular capillary, now we have a situation which is more analogous to what we see the rest in the body. And that is, post the, after the efferent arteriole, the hydrostatic pressure is now lower than the oncotic pressure. This means that the oncotic pressure is attracting water back into the peritubular capillary. And that occurs all the way along the peritubular capillary. And so that occurs all the way along the renal tubules. And this is then reabsorption, we're removing fluids then back into the blood. all the way along this the renal tubule. This is particularly important within the proximal convoluted tubule. So, if you consider the proximal convoluted tubule, and that's what's drawn here, I've drawn 2 of the cells, the epithelial cells, of this, of this region. Where the lumen is here and the blood is here, the blood space is here. And there's a very small interstitial space between the cells, the basal section of the cells, the basal surface, and, and the blood capillary. And this of course is our, the blood capillary is our paratubular capillary. The cells that line this tubule region in the proximal convoluted tubule are asymmetric in in expression of transporters. Such that transporters which are located on the luminal surfaces of these cell are different from the transporters which are located on the basal surface of the cells, or the surface that is facing the blood. And what I've diagrammed here is one such transporter, and this is the glucose sodium transporter. So, this is a co-transporter and it's a sim-porter, it's moving glucose and sodium in the same direction. As, as the sodium is moving into the cells, the glucose is piggybacking on to this on to this movement. And then the glucose, once it's in the cell can exit at the basal surface of the cells, and enter into the blood, simply going down its diffusion gradient. The sodium is also moving down its diffusion gradient due to the action of the sodium potassium actpa's which is located on the basal surfaces of these cells. Where we are extruding sodium in an active manner, we're using ATP to move 3 sodiums out of the cell for 2 potassiums to enter the cell. When we have a system where we have a co-transporter, which is which is linked to an active transport of one of the solutes that the co-transporter is using. Then, this is called secondary active transport. And, and as, if you recall, we discussed these in the second lectures of this course. Now as we're moving the sodium and the, and the glucose across these cells, we're generating an osmotic gradient. And so water will then move down it's osmotic gradient across the cells. We have aquaphor channels present within the luminal surfaces of the cells. So water then will follow the sodium to enter into the blood. And the movement of the, of these ions of the sodium and the glucose will be isoosmotic as it's moving from the lumen to the blood. The same thing will happen for movement of amino acids and for other small solutes going across this particular region. Now one of the other important items that has to be moved from the luminal surface, from the lumen, from the filtrate is got to be, is, is bicarbonate. So the bicarbonate is freely filtered as are protons, and they will enter into the tubule lumen. And in the tubule lumen on the surfaces of these, of these cells, the the proximal convoluted tubule epithelial tubules, epithelial cells, we have carbonic anhydrase activity. Carbonic anhydrase, as you, as you remember, will generate water and CO2 from a proton and bicarbonate. And the proton in the, bicarbonate cannot move into the cells but the water in the CO2 can freely enter into the cells. Once they're inside, then we would regenerate the proton in the bicarbonate because there's carbonic anhydrase activity within the cells. The bicarbonate is removed from these cells using the anti porter which is the bicarbonate chloride anti porter which is located in the basal region of these cells and bicarbonate enters into the blood. The proton is going to be extruded from the cells back into the lumen of the tubule, an this will occur in exchange for sodium. So this is an antiporter. The proton is leaving, back into the tubule, and sodium answers the cells. Now the rate of transport of materials across this region is saturable because we are using transporters. And that's what's shown here. So as with increase in the solute concentration which is along our, our x axis, is as that increases then the transport rate which is shown here on the y axis is increasing linearly. But eventually we saturate all the transporters and at that point, we then have a maximal maximal saturation of the transporters. And so we have maximal rate of transport of material. When this occurs, and we have maximal, we have all of the transporters occupied, we are then said to be at threshold for that particular substrate. So, for instance, if we're talking about glucose, as you all know, glucose is freely filtered. It enters into the filtrate, and all of the glucose will be reabsorbed across the approximal convoluted tribule and none will be found on, in the urine. But in the cases of an individual has Diabetes Mellitus , they have very high levels of circulating plasma glucose, and this plasma glucose, when its filtered and enters into the filtrate. Then binds to the transporter for the sodium of glucose transporters. And will actually a saturate all of the transporters. So any of the glucose which is left over which cannot bind to the transporters, stays in the renal tubule and it is then delivered to the, to the later regions of the tubule which do not have transporters for sodium and glucose. That means that the glucose and the so, and the glucose then, remains within the lumen of the tubule. It holds water because it's osmotically active. And these individuals then are going to have a problem, they're not going to be able to concentrate the urine. So they, they will urinate frequently and they'll be constantly thirsty. So some of the terms that you need to, to keep in mind then, is one, the transcellular movement. And transcellular movement is moving a material cross the cells, going from the lumen, across the cells and into the blood. This is usually done by secondary active transport within the proximal convoluted tubule. And, and this is the region where almost all of the secondary all of the materials that are within the filtrate are reabsorbed and moved back into the blood. Then use all of the glucose, all of the amino acids, even a very small proteins are broken down to amino acids and moved across in this region. and we have, we have, a, the movement of chloride, and urea. The chloride and urea will move by facilitated diffusion. because as we're moving ions and glucose and so forth, this are osmotically active particles. Then move across the cells, water follows them and then the chlo, the chloride and the urea becomes more concentrated within the filtrate, that generates a diffusion gradient for them. So they now are higher within the lumen, the concentrations are higher in the lumen, and they can then move across the cells to enter into the blood. The second type of movement, we've never discussed. And this is called paracellular movement. Paracellular means that we're going between the cells. So, if we, if I draw 2 of these cells, the cells are connected on the lumenal surfaces by what are called tight junctions. The tight junctions are little seals that prevent the lumenal content from leaking across between the cells to the blood. And the blood surface is over here. This is extremely important in the gut, where we have we have, one cell connected to the other, and all of the uptake of material from the gut across, has to occur across the cells to get into the, into the blood. In the kidney however, these tight junctions are a little leaky. And they're leaky to water. So water can move across the tight junctions in a paracellular manner, that is between the cells. With water is moving between the cells it is also setting up a concentration gradient for potassium. We do not have transporters for potassium located within the proximal convuluted tubule. And here as the potassium concentration rises. It now generates a gradient, a concentration gradient for potassium to diffuse, to diffuse across this region. But, potassium diffuses between the cells, so it's going, it's going in a paracellular manner. But the potassium is an ion that, that is very important to the body. And it actually has its own special name. And we call that solvent drag. But the solvent drag is a pair of cellular movement of potassium. And it's the, it's the movement of potassium between the cells. And it's moving because the, as we move water across these cells, we concentrate the potassium within the renal tubule. So, let's switch gears slightly and talk about secretion. Secretion as you recall is the movement of materials from the blood space across the renal tubular epithelium and into the filtrate itself. The secretion that I want to talk about is in the proximal convoluted tubule. So this is the same region we were talking about what, about what, just few minutes ago where the majority of reabsorption of ions, water, so forth, is occurring in the proximal convoluted tubule. With the secretion we're going to be moving materials that is directly from the peritubular capillary across the cells and into the lumen of the tubule. And the materials that we are moving are going to be organic compounds. These are going to use transporters which are sort of, generic transporters, and they are located on the basal surfaces of the cells. So the generic transporter then is allowing this material to go from blood into the lumen of the tubule. This again we're going to be using secondary active transport as our means for moving this material. And the transporters which are located on the, on the basal surfaces of the cell are absent from the luminal surfaces of the cell. So the transport is unidirectional, and again, transport is going to be saturable, because we have a finite number of transporters located within this region. So what are some of the materials that we move through the secretion? And one of them is that you move epinephrine, you also move norepinephrine through this region. Vitamins are taken across and cleared from the blood by secretion. Vitamins such as vitamin A, vitamin D, and so forth. We also have a, an instance where we're removing drugs. And drugs such as morphine and penicillin are secreted. So they are moving from, directly from the peritubular capillary across the proximal convoluted tubule epithelial cells, and into the lumen. And then, they will then be removed from the body in the urine. Now there is this, this special case of secretion that I wanted to talk about just briefly is that of potassium. So in the collecting duct, we have a cell that was just called a principal cell. This principal cell is also located in the, in the later region of the distal convoluted tubule. The principal cell reabsorbs sodium, that is it's moving sodium from the lumen, from the filtrate, then across these cells and into the blood space. And in exchange we're going to be moving potassium from the blood, across the cells, and into the lumen. So you notice that there's no charge gradient that's going to be established. We're just simply moving a positive ion, sodium, from one side to the opposite, and then moving potassium, which is a positively charged ion in the opposite direction. Now the, this entire region is using a sodium channel which is moving the sodium which is allowing the sodium to enter the cells, moving down this concentration gradient which is established, of course, by our sodium potassium ATPAs. The potassium is moving in the opposite direction. It is entering into the filtrate, and it is doing so also down its concentration gradient. As the sodium is extruded by the sodium-potassium ATPase, we're moving 2 potassiums into the cell. So we're increasing the gradient then, for potassium in the inside of the cell And we can then have potassium diffuse through this channel out into the lumen. So if we deliver a lot of sodium to this region, a lot of sodium into this collecting duct, then we will drive the, this movement of sodium into the cells and across the cells and into the blood. And that of course will drive the sodium potassium ATPase, and by doing so we then increase the intra, intracellular gradient for potassium. Potassium then will exit at a faster rate from the cells. So it's a way then of, of removing potassium from the blood in this particular region. Now, this particular region can also increase the removal of potassium by simply increasing the filtration flow through this area. And that is that, as the sodium is being delivered the sodium delivery is not as important as the potassium. We wash away the potassium and now the gradient for the potassium to exit the cells is increased, and the potassium then will leave the cells at a faster rate. This will then drive the sodium po, the sodium potassium ATPase and we will then lose potassium into the blood. So we have 2 ways then, of increasing the secretion of potassium. One is to have a delivery of high amounts of sodium to this region. And secondly, is to increase the filtrate flow in delivering a high filtrate flow to the collecting duct. Now the hormone aldosterone as you all recall is secreted by the adrenal glands. And this hormone regulates potassium levels within the body. This aldosterone is increased, secretion is increased when potassium rises within the blood. And the, and what aldosterone is doing is that it's acting on these principal cells within the kidney. It's increasing the copy number of the sodium channel of the potassium channel, and of the sodium-potassium ATPase. So, it's driving this entire system. And that's the way that aldosterone then is able to, to remove potassium from the blood. So what are our general concepts? So the first is, is that reabsorption moves to the filtered solutes from the renal tubule back to the blood. The second is that this reabsorption of solutes occurs predominantly within the proximal convoluted tubules. That's our major region for uptake of water, for sodium, all of glucose, all of the amino acids and so forth. Third, most of the solutes will cross this epithelium in a transcellular manner and it will be so by secondary active transport. Four, we have re-absorption within the proximal convoluted tubules occurs isosmotically. And that the water cross the epithelium via the aquaporin channels. Which are inserted within the lumenal region of the cells. And water can also cross in a paracellular manner. And that is between the cells, across those leaky tight junctions. And the potassium will move by solvent drag in a paracellular manner. So it's following the water in a paracellular manner. And that is, as water is moving, it's changing the concentration of the potassium in the tubule, and the potassium now has a higher concentration in the tubule, it can then diffuse across the cell, across this region and into the blood. Five, secretion is the movement of solutes from the blood to the lumen. And this, again, occurs in the proximal convoluted tubule, and, again, predominately by secondary active transport. And these are our organic molecules; our drugs, vitamins, and so forth. And then six, the secretion of potassium occurs in the collecting duct and also in the distal regions of the, of the distal convoluted tubule. And this is in response either to an increased sodium delivery to this region or to a high filtrate flow. And that importantly aldosterone acts on, on these cells, the principle cells, within this region to increase the channels for potassium, the channel for sodium and also the sodium potassium ATPase. And so it drives then the movement of potassium from the blood and into the, into the lumen of the tubule and then eventually to be excreted by the urine. In the urine. Okay, so the next time we come in here then, we're going to deal with the movements of water across the system. Okay, so see you then.
