Glomerular Filtration, Renal Blood Flow, PDF

Hey, everyone. Uh, this is the filtration, renal blood flow and their control. And this is, of course, Guyton. Chapter 27. Almost 180l a day are filtered from the glomerular capillaries in the Bowman's capsule. Most of this is reabsorbed, leaving only about one liter of fluid be excreted. But this i...

Hey, everyone. Uh, this is the filtration, renal blood flow and their control. And this is, of course, Guyton. Chapter 27. Almost 180l a day are filtered from the glomerular capillaries in the Bowman's capsule. Most of this is reabsorbed, leaving only about one liter of fluid be excreted. But this is highly variable depending on fluid intake. This also depends upon kidney blood flow as well as the glomerular capillary membranes. We will discuss further what determines GFR, filtration rate and renal blood flow. Similar to other capillaries, the capillaries are relatively impermeable to proteins and red blood cells. The concentration of other constituents are similar to the concentration that are in the plasma, except for such substances that may be partially bound to plasma. As we have discussed before, molecules that are bound to proteins do not diffuse easily. The capillary filtration rate is about 20% of renal plasma flow. This is due to the capillary filtration coefficient and balance of hydrostatic and colloid osmotic forces acting across the capillary membrane. I brought back the starting forces illustration from module one. The filtration fraction equals the common area filtration rate over renal plasma flow. Obviously, this is a ratio that can be increased by increasing GFR or decreased by decreasing renal plasma flow. It averages about 0.2, meaning 20% of the plasma flowing through the glomerulus is filtered to the renal tubules. This comes up in a few chapters. Capillary membranes have three major layers the endothelium, the basement membrane, and the epithelial cells. These layers make up the filtration barrier. The high filtration rate across the capillary is due to its perforation of thousands of small holes called Finisterre, which are similar to the finished rated capillaries found in the liver. Although smaller, these finished stations are similar. They are relatively large, but do not allow the cell proteins to pass, because the cell proteins have fixed negative charges that hinder their passage. The basement membrane surrounding the endothelium also has strong negative electrical charges that hinders the negatively charged proteins, but allows water and small solutes to pass. Photo sites also encircle the capillaries, although they have slit pores, uh, through which the filtration can move. Lastly, the epithelial cells are also negatively charged, preventing plasma protein passage. Despite its high filtration rate, the glomerular filtration barrier is selective in determining which molecules will be filtered based on their size and electrical charge. Water is freely filtered, but in size increases. Filter ability decreases. The pores of the glomerular membrane are thought to be about eight nanometres, and albumin is the only is only about six nanometers, but due to albumin negative charge, albumin filtration is almost zero. You can note in this graph that DAC strains manufactured with positively charged molecules are filtered much more readily than negatively charged molecules. The light can become permeable to plasma proteins due to a disruption of the poteau sites. This could be caused by an abnormal T-cell response and secretion of cytokines that injure the sites, increasing permeability to lower molecular weight proteins, especially albumin. This allows the proteins to be filtered into Bowman's capsule and causes proteinuria or output albuminuria. So Mario's filtration rate is determined by the sum of the hydrostatic and colloid osmotic forces, which gives the net filtration pressure and the glomerular capillary filtration coefficient. Camaro filtration equals the Gomery. The filtration coefficient times the net filtration pressure. The filtration pressure is the sum of the hydrostatic and colloid osmotic forces that favor or oppose filtration. This includes the Camaro capillary hydrostatic pressure, the hydrostatic pressure in Bowman's capsule, the colloid osmotic pressure in the capillary, and the colloid osmotic pressure of proteins in Bowman's capsule. Although, as we discussed, the concentration of proteins in Bowman's capsule is typically so low that the colloid osmotic pressure is considered to be zero. CF cannot be measured directly, but is calculated to be normally 12.5ml a minute, which is about 400 times higher than any other capillaries in the body. It is the product of the hydraulic, uh, hydraulic productivity and surface area of the commercial capillaries. Changing the CF can change the GFR, but this is probably not a primary mechanism for the daily regulation of filtration. Although some diseases can reduce the number of functioning glomerular capillaries and therefore reduce the surface area for filtration, reducing the GFR. Increasingly, hydrostatic pressure in Bowman's capsule reduces GFR, whereas decreasing the pressure raises GFR. Although this does not normally serve as a primary means for regulating GFR, pathologic conditions such as obstruction of the urinary tract can cause increased pressure in Bowman's capsule, seriously reducing filtration. As blood passes from the afferent arterials through the capillaries to the efficient arterial, the plasma protein concentration increases about 20% due to the removal of fluid for filtration. This causes the colloid osmotic pressure to raise from 28 to 36mm of mercury. Therefore, the average colloid osmotic pressure is about 32. Two things that influence SQL Mario Catholic. Colloid osmotic pressure or the arterial plasma. Colloid osmotic pressure and the fracture fraction of plasma filtered by the glomerular capillaries. Increasing the arterial plasma. Colloid osmotic pressure decreases the amount of filtration. Of course, the inverse can occur that decreases the arterial plasma colloid osmotic pressure, or decrease the commercial colloid osmotic pressure and increase filtration. Yet the filtration rate is raised. It causes concentration of plasma proteins and an increase in the capillary osmotic pressure, and therefore a reduction in GFR. The area called osmotic pressure can also be changed by changing the renal plasma flow. A reduction in renal plasma flow increases the filtration fraction and raises the colloid osmotic pressure, which then reduces GFR. Changes in glomerular hydrostatic pressure serve as the primary means for physiologic regulation of GFR. Increased hydrostatic pressure raises GFR. Hydrostatic pressure is determined by three variables arterial pressure, afferent arterial resistance, and arterial resistance. Increased arterial pressure raises glomerular hydrostatic pressure and therefore increases GFR. However, other regulatory mechanisms maintain a relative constant glomerular pressure, uh, as arterial pressure fluctuates. Increased resistance of the afferent arterials decreases glomerular hydrostatic pressure and GFR. Constriction of arterials increases resistance to outflow and raises hydrostatic pressure. However, if arterial constriction is severe, it causes colloid osmotic pressure to rise a greater degree than capillary hydrostatic pressure, and this actually decreases the net filtration force, causing a reduction in GFR. In summary, if our tibial constriction has a biphasic effect, if constriction is slight, it causes increased filtration through an increase in hydrostatic pressure. But if resistance increases more than three fold, colloid osmotic pressure increases and GFR decreases. A good way to test yourself for these concepts is to explain the arrows in this chart from page 336 and Guyton using Starling forces. Then add in this chart from 337 and explain these hormones or drugs with starling forces as well. Renal blood flow is determined by the pressure gradient across the Or vasculature, which is the difference between the renal artery and renal vein hydrostatic pressures. This is represented by the formula. Here, most of the renal vascular resistance resides in three major segments the inter lobular arteries, the afferent arterials, and the arterials. Resistance of these vessels is controlled by the sympathetic nervous system, various hormones, and local internal renal control. An increase in resistance in any of these segments reduces blood flow, and a decrease in resistance increases blood flow. The renal cortex receives most of the kidneys blood flow. Um. So if you look on this image here, the cortex would. As the outer portion of the kidney. So this is the cortex. And whereas this inner portion. Is the medulla. And then this is the renal pelvis. You can see here. So. Renal pelvis. Blood flow to the renal medulla accounts for only 1 to 2% of total renal blood flow. Blood flow to the medulla is supplied by the phase erector. So we talked about the pace of rector a little bit before the visa erected, descends into the medulla parallel with the loops of Hindley, and then returns along the loop of Hindley to the cortex before emptying into the venous system. And you can see it here descending with the loop of Hindley, and then returning and emptying into the venous system. The most important determinant of GFR, that is, the one that is most variable and controllable is the column hydrostatic pressure. It is heavily influenced by the sympathetic nervous system, hormones, dacoits and other feedback controls. Most blood vessels in the kidney, especially the afferent and inherent arterials, are richly innervated by sympathetic nerve fibers. Strong activation of renal sympathetic nerves constricts renal arterials and decreases renal blood flow and GFR. Mild to moderate stimulation of the sympathetic nervous system has little influence on renal blood flow and GFR. Although mild to moderate stimulation causes random release and increased renal tubular reabsorption, causing decreased sodium and water excretion. Norepinephrine, epinephrine, and endothelium constrict afferent and arterials, causing reductions in GFR and renal blood flow. In general, blood levels of these hormones parallel the activity of the sympathetic nervous system. Endothelium is released by damaged vascular endothelial cells and may contribute to hemostasis when blood vessels are severed. Angiotensin two is a circulating hormone as well as locally produced article. It is formed in the kidneys and is. This is in the systemic circulation. Angiotensin two receptors are present in all the blood vessels of the kidneys. However, the blood vessels are protected from its effect. Vasodilators, especially nitric oxide and prostaglandins, counteract the vasoconstrictor effects of angiotensin two. In the pre glomerular vessels, however, the efferent arterials are highly sensitive. Therefore, angiotensin two raises glomerular hydrostatic pressure while reducing renal blood flow. This reduction of blood flow while also increasing glomerular hydrostatic pressure, causes increased reabsorption of sodium and water. Therefore, GFR and excretion of waste products are maintained. Endothelial derived nitric oxide is produced throughout the body. It decreases vascular resistance. A basal level of nitric oxide production appears to be important for maintaining vasodilation of the kidneys, and normal and the normal excretion of sodium and water. Therefore, drugs that inhibit nitric oxide formation will increase renal vascular resistance and decrease GFR. Some hypertensive patients or patients with atherosclerosis may have damage to the vascular endothelium and impaired nitric oxide production. I pause here to kind of review this. Uh, under the influence of arginine. So you see arginine here. Uh, nitric oxide causes the conversion of GTP to cyclic GMP, which causes vasodilation by interacting with with the phosphodiester forces. Um, this will reduce the concentration of intracellular calcium and cause vasodilation. Uh, this mechanism is important for many drugs who use um or. Or, uh, being interaction from other drugs that people are using that are interact with the drugs that you use. Uh, it's also important how to, to learn how to, uh, read these diagrams. So a stimulation, an agonist stimulates a receptor. Arginine stimulates nitric oxide production. Nitric oxide is a gas and can diffuse through cellular membranes. Uh, it acts at um GTP for the conversion from GPD. It really acts here GTP to cyclic GMP and causes phase of dilation to relaxation of smooth muscles because of decreased calcium. Renal blood flow and GFR are normally held relatively constant, despite marked changes in arterial blood pressure. This is referred to as auto regulation. Typically, in most tissues of the body, the goal of auto regulation is to maintain the delivery of oxygen and nutrients and to remove waste products of metabolism. Although in the kidneys, normal blood flow is much higher than required for these functions, and therefore the regulation of renal blood flow is to maintain a relatively constant GFR and control renal excretion of water and waste. Uh, this graph has a lot of information in it, so let's unpack it a little. Uh, first, uh. You see that with increasing your pressure, there's increasing urinary output. You see the increasing urinary output, uh, with increasing pressure. Uh, which is exactly what you would expect. But most importantly for our talk right now, um, you see that with a mean pressure between 50. And just about 200. Um. That GFR remains relatively constant throughout. So lots of auto regulation here to be able to maintain between the mean arterial pressure of 50 and 200. Auto regulation prevents potentially large changes in GFR and renal excretion of water and solutes that would otherwise occur with changes in blood pressure. Uh, let's go over a quick math problem to illustrate this. Uh, normally GFR is about 180l a day, and tubular reabsorption is 178.5l a day, leaving 1.5l to be treated as urine. Without auto regulation, only a small 25% increase in blood pressure. GFR would increase from about 180 to 225l a day, but tubular reabsorption remains constant at 178.5, and therefore urine output increases to 46.5l a day. Since the total plasma volume is only about three liters, uh, this change would quickly deplete that. In reality, changes in arterial pressure have much less effect due to auto regulation and adaptive mechanisms in the renal tubules that cause them to increase the reabsorption rate when GFR rises. Even with control mechanisms, though, changes in arterial pressure have significant effects on the excretion of water and sodium. This is referred to as pressure diuresis and pressure naturally, which is crucial for the regulation of body fluid volumes and arterial pressure. We will discuss this more later extensively. There is a special feedback mechanism that links changes in the sodium chloride concentration at the macula, denser with control of renal arterial resistance and auto regulation. This helps ensure a relatively constant delivery of sodium chloride to the distal tubule, and prevents fluctuations in renal excretion. Most times, this regulates renal blood flow and GFR simultaneously. Although the goal is to stabilize sodium chloride delivery to the distal tubule. Therefore, GFR may be regulated at the expense of renal blood flow. This tubular glomerular feedback mechanism has both an effort and effect. Arterial control mechanism. Um. This feedback is dependent upon the special anatomical location of the macula and jux to get married, or cells that are located in the walls of the initial portion of the distal tubule. So pause here. So macula denso denser is in the initial portion of the distal tubule. You can see the distal tubule here back vascular located here. Um. And the effort and effort arterials. Um, and you can see how the macular denser is sitting here next to the afferent and efferent arterials. And, uh. This specialized group of epithelial cells contains a Golgi apparatus, uh, which, if you remember, the Golgi apparatus from, uh, module one, uh, back a few modules ago. Uh, Secretary functions of the cell. Um. This Golgi apparatus is directed towards the arterials. This suggests that these cells are secreting a substance in that direction. So there's a substance that these gorges are to create. Are secreting towards the arterials here and there. Close proximity and anatomical locations is what allows this control. A decreased GFR, uh, causes a decreased flow rate through the loop of Henley. This causes increased reabsorption of sodium and chloride, since the macula, denser, sits following the loop of Henley. A decreased sodium concentration is delivered to it, so once again the immaculate, denser following the loop of Henley, come back around, uh, in the proximal distal tubule. Um. The macular denoiser then sends a signal. Uh, the signal has two effects. The afferent arterials relax, decreasing resistance to blood flow and raising jeux. Glomerular hydrostatic pressure in renin is released from its main storage sites in the drugs to grow glomerular cells of the afferent and event arterials, of course, uh, the renin pathway renin is converted to angiotensin one, which is then converted to angiotensin two. Angiotensin two causes uh restriction constriction of the efficient arterials, increasing glomerular filter, uh, GFR um area filtration rate. So decreased start to your pressure decreases uh, glomerular hydrostatic pressure. Of course that decreases GFR. That increases, uh, absorption in the loop of hennelly, uh, sodium reabsorption in the loop of Hennelly. So there's in or decreased amount of sodium chloride in the macula denser. This causes increased renin release and, uh, relaxation of the afferent arterials. Of course, renin is converted to angiotensin two um eventually which causes efferent arterial constriction and increased resistance, which increases GFR. Uh.