Renal Tubular Reabsorption and Secretion PDF

In some parts of the tubule, especially the proximal tubule. Reabsorption of large molecules such as proteins, occurs via pino ptosis. In the tubular lumen, the protein attaches to the brush border, the brush border, then endogenous, and encapsulate the protein, forming a vessel. Once inside the cel...

In some parts of the tubule, especially the proximal tubule. Reabsorption of large molecules such as proteins, occurs via pino ptosis. In the tubular lumen, the protein attaches to the brush border, the brush border, then endogenous, and encapsulate the protein, forming a vessel. Once inside the cell, the protein is digested into its constituent amino acids, which are then reabsorbed through the basal lateral membrane. Since Pino said ptosis requires energy, it is considered active transport. I'm sure you remember this slide from chapter two. The filtration is non-selective. That is, if a substance is not bound to protein, it is filtered. Ethical Mary lists the amount dependent upon its concentration in the plasma. There is a large amount of glomerular filtration as compared to urine. Therefore, there is a high amount of tubule reabsorption as compared to urinary excretion. This means that a small change in glomerular filtration or tubular reabsorption can cause a large change in urinary excretion. We discussed this before when we discuss glomerular filtration. The same principle applies to tubular reabsorption. For example, a 10% decrease in tubular reabsorption would increase urinary volume from 1.5 to 19.3 liters a day. This tubular reabsorption is highly selective. Some substances, such as glucose and amino acids, are reabsorbed almost completely, whereas others, such as sodium and chloride, are variable depending on the needs of the body. And lastly, in the last category, waste products such as urea are poorly reabsorbed and excreted in large amounts. The mechanism for reabsorption can be controlled independently of each other, allowing the selective reabsorption or secretion of individual substances. In the image, you can see different paths for reabsorption from the tubular lumen, across the tubular epithelial cells, through the renal interstitium, and back into the blood. Now we can start to talk about those mechanisms. More specifically, to be reabsorbed, substances must first be transported across the tubular epithelial membrane into the renal interstitial fluid, and then through the peer to peer capillary membrane back into the blood. This can involve active or passive transport. So they must go from. The, uh, tubular lumen, uh, where you have filtrate and it must go through either the trans cellular or the cellular pathway, uh, through the brush border into the tubular cell and then transported out of the tube or cell into the. Interstitial fluid and then through pressures into the blood. Um. These solutes can pass through the cell membrane or through the spaces between the cell junctions. And so this is the cellular pathway that in between the cell junctions um passes through the tubular capillary walls. And the blood is mediated by hydrostatic and colloid osmotic pressures similar to venous pressures. Uh venous reabsorption we have discussed before. So that's where this occurs is the venous reabsorption. This picture on the bottom left gives a little better visual representation of the spaces. It shows of course the tubular lumen the tubular epithelial cells the basement membrane the interstitial fluid which is important. It's not represented here. It just shows the bulk flow here in this big image. But you can see the interstitial fluid here. And it kind of makes a better visual representation. Um, and then of course the period tubular capillary here. Uh, so the transport of solutes here is mediated by these pressures that we've discussed before. Active transport moves of solute against an electrochemical gradient and requires energy. An example of this is a sodium potassium ATPase pump. You can see an image of the sodium potassium ATP pump here. Energy is needed to transport sodium potassium against its electrochemical gradient. So here's the sodium potassium ATPase pump. You're transporting sodium out of the cell, you know, against its electrochemical gradient and potassium into the cell against its electrochemical gradient. Um, secondary active transport is coupled indirectly to an energy source. For example, here with the glucose, um, it's coupled via a ion gradient. Um, the sodium potassium part we just discussed creates a low, um intracellular concentration of sodium. So by pumping the sodium out, a low concentration of sodium is intracellular. We've talked about that before. Um, this causes sodium to diffuse down its electrochemical gradient from the tubular into the cell. Um. It brings glucose with it. The transporter brings glucose with it from the tubule. So therefore the glucose is, uh, transported intracellular via secondary active transport. The same goes here with amino acids. Epithelial cells are held together by tight junctions. But behind these tight junctions by a pair of cellular pathway solutes can be reabsorbed through the trans cellular pathway, through the tubular cells or between the cells by moving across the tight junctions and then through the intracellular spaces through the pair of cellular pathways. So the visual representation pair cellular pathway in the trans cellular pathway, uh, for example, sodium moves through both routes, mostly through the trans cellular pathway, although in the proximal tubule water is reabsorbed across the of cellular pathway. Primary active transport moves solutes against an electrochemical gradient. For example, here with this ATPase pump across the proximal tubular membrane on the basal lateral side of the tubular epithelial cell. The cell membrane has an extensive system of the sodium potassium pumps that use energy from the ATP, from ATP, to transport sodium ions out of the cell and into the interstitium this creates. Low intracellular sodium and high intracellular potassium. Uh, creating a negative charge of -70 millivolts, uh, within the cell and a sodium concentration of around 12. I'm just going to write it up here. So it's separate 12 MCU. Intracellular as compared to 140 MQ. In the tubular lumen. Um, this creates a strong concentration gradient. Uh. From the tubular lumen into the cell. So this creates a strong drive, uh, strong concentration gradient for movement from tubular women to tubular epithelial cells. Uh, at the same time, this electrochemical, uh, electrical. Gradient drives sodium into the cell as well. The active reabsorption of sodium by the sodium potassium pump occurs in most parts of the tubule. Certain parts, uh, of the tubule. There are even more provisions for sodium reabsorption into the cell. For example, in the proximal tubule there's an extensive brush border. And you can see the brush border illustrated here. Um, on the luminal side of the tubular epithelial cells that multiplies the surface area for reabsorption by about 20 fold. Uh, in some areas, there's also carrier proteins that can provide facilitated diffusion of sodium. And we'll talk more about that. In summary, there are three steps for the net reabsorption of sodium from the tubular lumen into the blood. One sodium diffuses from the tubular lumen across the apical membrane down and electrochemical gradient established by the sodium potassium ATPase pump. Two sodium is transported across the basal outer membrane against an electrochemical gradient by the sodium potassium ATPase pump. Three sodium water and other substances are reabsorbed from the interstitial fluid into the paired tubule capillaries by a passive process driven by hydrostatic and colloid osmotic pressure gradients. In secondary active transport, two or more substances interact with a specific carrier molecule or membrane protein and are transported across a membrane. One of the substances in this illustration, sodium uh, diffuses down its electrochemical gradient, providing the energy to drive another substance against its electrochemical gradient. Therefore energy is not required directly from ATP. In this image, sodium is transported from the tubular lumen down its concentration gradient. Um. Which provides for the secondary active transport of glucose and amino acids. Uh, in the proximal tubule. This requires a specific carrier protein in the brush border that combines with a sodium ion and an amino acid or glucose molecule. At the same time, after entering the tubular cell, the glucose and amino acids exit the basal basal membrane by diffusion, driven by their high interest concentration. The sodium and glucose cotransporter in the brush border are referred to as Sgt one and two transporters. 90% of the filtered glucose is reabsorbed by GT two transporters and the other 10% by GLP one uh. Later, in the proximal tubule on the basal lateral side, glucose diffuses out of the cell with the help of a glucose transporter. Uh, here. Or it's referred to as glute one and glute to their transport on the basal lateral side does not directly use ATP. ATP, although is dependent upon energy expended by the sodium potassium pump maintaining the electrochemical gradient. Thus glucose is secondary active transport because the glucose is reabsorbed against its concentration gradient. Here. Uh, but the energy it uses is secondary to the primary active transport of sodium. Any time a step in the process is through secondary active transport, the entire process is referred to as secondary active transport. For example, the glucose reabsorption at the luminal membrane is down here. This at the luminal membrane is down. Um. Its concentration gradient, but it is dependent upon the secondary active transport from the tubular lumen. Therefore, both steps are referred to as secondary active transport. So both these steps, even though this one is down its concentration gradient, is referred to a secondary active transport. Some substances are secreted into the tubules by secondary active transport, which often involves counter transport of the substances with sodium ions. Energy is created by the downhill movement of one substance. In this image. Sodium. So here, uh, which enables the uphill movement of a secondary substance in the opposite direction here with hydrogen. Uh, the example here is the counter transport and act of secretion of hydrogen ions that is coupled to sodium reabsorption. This is mediated by the sodium hydrogen exchanger protein. In the luminal membrane of the proximal tubule, a sodium ion is transported to the interior of the cell. Why? While hydrogen ions are forced outward into the tubular lumen. For most substances that are actively reabsorbed. There is a limit to the rate at which this reabsorption can occur. This limit is due to the saturation of the specific transport systems. When the tubular load exceeds the capacity of the carrier proteins and specific enzymes involved. Glucose reabsorption is a good example. When the filtered glucose exceeds the capacity of the tubules to reabsorb it. Urinary excretion occurs. The transport maximum for glucose is about 375mg a minute, whereas the typical amount of filtered glucose is only 125mg a minute. But with large increases in GFR or plasma glucose concentration, the amount of glucose in the tubule can exceed this 375mg a minute. You can see on the graph that as the filtered load increases, transport increases. So here you, uh, filtered and transport together. Um. Until it becomes close to the plateau, which is, uh, the transport maximum, so that here you have the plateau, uh, the transport maximum. Um, glucose appears in the urine slightly before the transport maximum was reached. Since not all nephrons have the same transport maximum and some excreted glucose occurs before others, some glucose excretion occurs before others in certain nephrons. Of course, when filtered load as above. Reabsorption limits, uh, the rest will be secreted. This is shown with the green excretion line. So you can see the excretion increases in the urine as you reach, uh, the transport maximum. Um, as the filtered load increases. Some substances that are actively reabsorbed do not demonstrate a transport maximum. This occurs when the rate of transport is determined by other factors such as the electrochemical gradient, the permeability of the membrane for the substance, or the time that the substance remains within the tubule. This, of course, depends on the tubular flow rate. For example, in the proximal tubule, the reabsorption of sodium is usually far greater than the actual rate of sodium reabsorption, because sodium leaks back into the tubular lumen through loose junctions. Therefore, sodium transport in the proximal tubules obeys mainly gradient time transportation principles rather than transport maximum rates. The higher the concentration of sodium in the tubule lumen, the more reabsorption takes place. So, uh, sodium leaks back through. Uh, the Epatha junctions are back in the tubule lumen. So the higher the concentration here in the tubular lumen, the less will leak back, because it is opposed by this concentration gradient, uh, in more distal parts of the nephron. The epithelial cells have a much tighter junction. And these areas exhibit transport maximum because it's dependent upon this mechanism. Transport maximums can also be influenced by hormones such as aldosterone. When solutes are transported out of the tubule by any mechanism, their concentrations inside the tubule will decrease, while at the same time, concentrations inside the renal interstitium will increase. This creates a concentration difference that causes osmosis in the same direction. The proximal tubule is highly permeable to water, and water reabsorption occurs so rapidly that there's only a small concentration gradient for solutes across