Welcome back. So, today we want to talk about the renal system. This the third of our lectures about the renal system. The things that we want to discuss today, are how the kidney uses tubular transporters to reabsorb materials, that is to take solutes from the filtrate back into the body, into the blood. Also How does it secrete materials bypassing the filtration route that we talked about the last 2 times. So, the specific learning objectives are first to explain the importance of the peritubular capillary in the kidney cortex. The second, 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. We're going to use glucose transport as our example. Then very briefly, we'll talk about moving bicarbonate across these cells. Third, we want to talk about transcellular transport, that is the movement across cells versus movement between cells, the paracellular pathways. We will consider how water will move across this particular region of the kidney. 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 items that use transporters. And five, we'll consider the process of secretion. Secretion of organic compounds very briefly and then in particularly secretion of potassium. So let's revisit the tubule That is what is diagrammed here. We have an afferent arteriole, which is feeding into the glomerulus,our first capillary bed. That first capillary bed is drained by a second arteriole, the efferent arteriole. The blood then drains into a second capillary bed, called the peritubular capillary. The peritubular capillary runs along the renal tubule within the cortex and medulla of the kidney. We also have the renal tubule. That's what's diagrammed here. Circling around the glomerulus, is Bowman's capsule. That is this. From Bowman's capsule, we enter into the rest of the renal tubule. The first region is the proximal convoluted tubule. Then we'll go through the Loop of Henle and eventually the distal tubule and the collecting duct. This connects to the ureter. So the process of generating urine begins between the glomerulus and Bowman's capsule. At this site we have this filtration. Filtration of the blood moves solutes and water into the lumen of the renal tubule. This process is governed by specific pressures. The vascular hydrostatic pressure minus oncotic pressure and Bowman's capsule pressure. Once the fitrate formed, many solutes and water move from the renal tubule back into the blood. This process is very important. Because within 24 minutes, we can completely exhaust the cardiovascular system if we do not bring the fluids, water in particular, back into the blood. We also need to balance ions in the blood. In particular bicarbonate. Bicarbonate is filtered freely across the glomerulus. We need to move that bicarbonate back into the blood to use it as a ph buffer. This process is called reabsorption. Reabsorption is the main topic for today. THat is how we move solutes from the lumen of the tubule across the cells lining the tubule back into the blood. In addition, some solutes bypass filtration and move directly from the blood, from that peritubular capillary, directly into the renal tubule. THis process is called secretion. So what are the things that govern this particular region? These processes, reabsorption and filtration are governed by pressures. That's what's diagrammed here. So you recall, we have a portal system where the afferent arteriole, is on one side of the glomerulus, the first capillary bed, and then the efferent arteriole is on the other side of the capillary bed. That is different from what we see in most places within the body. Typically we have an arteriole feeding into a capillary which is then feeding into a venule. Within the nephron, both the afferent arteriole and the efferent arteriole are regulated. The diameter of the lumen of those vessels are regulated independently. First We can maintain the hydrostatic pressures within the glomerulus such that it always exceeds the oncotic pressure. When the hydrostatic pressure is higher than the oncotic pressure and it's higher also to the pressure in 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, we have a situation which is more analogous to what we see the rest in the body. That is, downstream of 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. That occurs all the way along the peritubular capillary. So that movement of water occurs all the way along the renal tubules. This is reabsorption. We're moving fluids then back into the blood all along the renal tubule. This is particularly important within the proximal convoluted tubule. Let's consider the proximal convoluted tubule. That's what's drawn here. I've drawn 2 of the cells, the epithelial cells of this region. The lumen is here. The blood is here inside the blood vessel. There's a very small interstitial space between the cells, the basal surface of the cells and the blood capillary. This of course is the blood capillary, our peritubular 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, the surface that is facing the blood. And what I've diagrammed here is one such transporter, and this is the glucose sodium transporter. This is a co-transporter. It's a symporter. It moves glucose and sodium in the same direction. As, as the sodium is moving into the cells, the glucose is piggybacking onto this movement. Then 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 ATPase which is located on the basal surfaces of these cells. Here sodium exits the cell in an active manner. We use ATP to move 3 sodium ions out of the cell for 2 potassium ions which enter the cell. This situation is one in which a co-transporter is linked to an active transport of one of the solutes that the co-transporter is using. This mechanism is called secondary active transport. If you recall, we discussed these transport mechanisms in the second lecture of this course. Now as we move the sodium ions and glucose across these cells, we generate an osmotic gradient. And so water then moves down it's osmotic gradient across the cells. Aquaporin channels are present within the luminal surfaces of the cells. So water will follow rapidly the sodium to enter into the blood. The movement of the sodium ion and glucose will be isosmotic as they move 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. One of the other important items that has to be moved from the luminal surface, from the lumen, from the filtrate is is bicarbonate. Bicarbonate is freely filtered, as are protons. These ions enter into the tubule lumen. And in the tubule lumen on the surfaces of the epithelial cells, the the proximal convoluted tubule epithelial tubules, is the enzyme carbonic anhydrase. Carbonic anhydrase, as you, as you remember, generates water and CO2 from a proton and bicarbonate. And the proton and bicarbonate ions cannot move into the cells. But water and CO2 can enter freely into the cells. Once they're inside, then the cell regenerates the proton and the bicarbonate using the carbonic anhydrase located within these cells. The bicarbonate is removed from these cells using an antiporter. The bicarbonate- chloride antiporter which is located in the basal region of these cells. Bicarbonate enters into the blood. The proton is extruded from the cells back into the lumen of the tubule. THis occurs in exchange for sodium. This is an antiporter. The proton leaves the cell enters into the tubule, and sodium exits the cells at. the base. The rate of transport of materials across this region is saturable because we are using transporters. That's what's shown here. With an increase in the solute concentration. Shown along the x axis. There is an increase in the transport rate. Shown here on the y axis. TRansport rate increases linearly. But eventually we saturate all the transporters. At that point, then we have maximal saturation of the transporters. So we have maximal rate of transport of material. When this occurs, all of the transporters are occupied. THis is called the threshold for that particular substrate. For instance, if we consider glucose. As you all know, glucose is freely filtered. It enters into the filtrate, and all of the glucose will be reabsorbed across the proximal convoluted tribule. None will be found in the urine. But in the case of an individual with Diabetes Mellitus. There is a very high level of circulating plasma glucose. This plasma glucose, when filtered enters into the filtrate. It binds to the co-transporter, the sodium-glucose transporter. The amount of glucose will actually saturate all of these transporters. Any of the glucose which cannot bind to the co-transporters, stays in the renal tubule. It is then delivered to the later regions of the tubule which do not have co-transporters for sodium and glucose. That means that the glucose remains within the lumen of the tubule. It holds water in the tubule lumen because it is osmotically active. Consequently these individuals have a problem. They are not able to concentrate their urine. They will urinate frequently and they will be constantly thirsty. Some of the terms that you need to keep in mind then are one, transcellular movement. Transcellular movement moves a specific substance across the cells. It goes from the lumen, across the cells and into the blood. This is usually done by secondary active transport within the proximal convoluted tubule. This is the region of the tubule where almost all of the materials within the filtrate are reabsorbed and moved back into the blood. That includes 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. We also have the movement of chloride ions and urea. The chloride ion and urea will move by facilitated diffusion. This can occur because as ions and glucose are removed, water follows. These are osmotically active particles. Water follows them. That means chloride ions and urea becomes more concentrated within the filtrate. THis generates a diffusion gradient for them. They now are higher within the lumen, their concentrations are higher in the lumen, so they can then move across the cells to enter into the blood by diffusion. The next type of movement, we've never discussed. This is called paracellular movement. Paracellular means that going between the cells. If I draw 2 of these epithelial cells, then notice the cells are connected on their lumenal surfaces by tight junctions. The tight junctions are little seals that prevent the lumenal content from leaking across between the cells to the blood. The blood surface is over here. This is extremely important in the gut, where we have one cell connected to the other, and all of the uptake of material from the gut has to occur across the cells to get into the, into the blood. In the kidney however, these tight junctions are a little leaky. They're leaky to water. So water can move across the tight junctions in a paracellular manner, that is between the cells. When water moves between the cells it sets up a concentration gradient for potassium ions. There are no transporters for potassium located within the proximal convuluted tubule. AS water exits, the potassium concentration rises. It now generates a gradient, a concentration gradient for potassium to diffuse across this region. But potassium diffuses between the cells. It goes in a paracellular manner. Because the potassium ion is very important to the body. This transport has its own special name. We call it solvent drag. Solvent drag is a paracellular movement of potassium. And it's the movement of potassium between the cells. It moves because of the movement of water across these cells. As water moves potassium becomes more concentrated in the renal tubule. 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 occurs in the proximal convoluted tubule. This is the same region we were considering just few minutes ago where the majority of of ions, water, so forth, is resorbed This is the proximal convoluted tubule. With the secretion, we are moving materials directly from the peritubular capillary across the cells and into the lumen of the tubule. The materials that are organic compounds. These compounds use transporters which are generic transporters. They are located on the basal surfaces of the epithelial cells. The generic transporter allows this material to go from blood into the lumen of the tubule. Again we're going to be using secondary active transport as our means for moving this material. The transporters which are located on the basal surfaces of the cell are absent from the luminal surfaces of the cell. So the transport is unidirectional. Again, transport is going to be saturable, because we have a finite number of transporters located within this region. What are some of the materials that we move through secretion? And one of them is that you move epinephrine, and also norepinephrine in 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 an instance where we remove drugs from the blood. Drugs such as morphine and penicillin are secreted. They move directly from the peritubular capillary across the proximal convoluted tubule epithelial cells and into the lumen. They will then be removed from the body in the urine. Now there is a special case of secretion that I wanted to talk about just briefly. That is potassium secretion. In the collecting duct, there is a cell called a principal cell. This principal cell is located also in the later portion of the distal convoluted tubule. The principal cell reabsorb sodium, that is sodium moves from the lumen, from the filtrate, across these cells and into the blood space. In exchange we move potassium from the blood, across the cells, and into the lumen. So you notice that there's no charge gradient that is 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. IN this entire region the sodium channel which moves the sodium ion is allowing the sodium to enter the cells, moving down the sodium concentration gradient which is established, of course, by our sodium- potassium ATPase. The potassium ion moves in the opposite direction. It enters into the filtrate. Potassium is moving down its concentration gradient. As the sodium is extruded by the sodium-potassium ATPase, then 2 potassiums enter into the cell. So we're increasing the gradient for potassium inside the cell Consequently potassium diffuses through the potassium channel into the tubule lumen. If we deliver a lot of sodium to this region, a lot of sodium into the collecting duct, then we will drive the, this movement of sodium into the cells and across the cells and into the blood. That of course will drive the sodium potassium ATPase, and by doing so we then increase the intracellular gradient for potassium. Potassium then will exit at a faster rate from the cells. So it's a way then 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. Now the rate of flow is important. The sodium delivery is not as important as the removal of potassium. We wash away the potassium from the cells quickly which enhances the gradient for potassium to exit the cells. The potassium then will leave the cells at a faster rate. This will in turn drive the sodium potassium ATPase. We will remove potassium from 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. This hormone regulates potassium levels within the body. Aldosterone secretion is increased when potassium rises within the blood. The target cell for aldosterone is these principal cells within the kidney. Aldosterone increases the number of sodium channel and potassium channels, and the sodium-potassium ATPases. It drives this entire mechanism. That's the way that aldosterone is able to remove potassium from the blood. So what are our general concepts? The first 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 do so by secondary active transport. Four, reabsorption within the proximal convoluted tubules occurs isosmotically. Water cross the epithelium via aquaporin channels. Which are inserted within the lumenal region of the cells. Water can also cross in a paracellular manner. And that is between the cells, across those leaky tight junctions. Potassium will move by solvent drag in a paracellular manner. It is following the water in a paracellular manner. That is, as water is moving, it changes the concentration of potassium in the tubule. Potassium now has a higher concentration inside 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. This, again, occurs in the proximal convoluted tubule. Again, this is predominately by secondary active transport. These moves organic molecules, 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. Importantly aldosterone acts on, on these cells, the principal cells, within this region to increase the channels for potassium, the channel for sodium and also the sodium potassium ATPase. Aldosterone drives then the movement of potassium from the blood and into the, into the lumen of the tubule and then eventually potssium is excreted in urine. Okay, so the next time we come in here we're going to deal with the movements of water across the system. Okay, so see you then.
