Urine Concentration and Dilution (G29)

Hi everyone. This is urine concentration and dilution. Uh, module three still, uh, gate in chapter 29. Kidneys have a tremendous capability to vary the relative proportions of solutes and water in the urine in response to changes in the body. When there is excess water in the body and osmolarity is...

Hi everyone. This is urine concentration and dilution. Uh, module three still, uh, gate in chapter 29. Kidneys have a tremendous capability to vary the relative proportions of solutes and water in the urine in response to changes in the body. When there is excess water in the body and osmolarity is reduced, the kidneys can excrete urine with osmolarity as low as $50 million, which is a concentration of about one sixth the osmolarity of normal body fluid. Conversely, when there is a deficit of body water and osmolarity is high, urine is highly concentrated with osmolarity of 1200 and $1,400 million per liter. At the same time, the kidneys can excrete a large volume of dilute urine or a small volume of concentrated urine without major changes in the rates of solute solute excretion. Antidiuretic hormone or vasopressin causes the kidneys to alter the excretion of water independent of solutes. When osmolarity of bodily fluids increases above normal, the posterior pituitary secretes more aids, which increases the water permeability of the distal tubules and collecting ducts. This alters the excretion of water and decreases urine volume, but does not change the excretion of solids. When there is excess water in the body, secretion of ADH by the posterior pituitary decreases, which reduces the permeability of the distal tubule and collecting ducts to water, and causes increased amounts of dilute urine to be excreted. When there's excess water in the body, the kidneys can excrete as much as 20l a day of dilute urine, with the concentration as low as $50 million per liter. Solutes are reabsorbed without re absorbing large amounts of water in the distal parts of the nephron, especially the late distal tubule and collecting ducts. 45 minutes after drinking one liter of water, the urine volume increases about six times normal. However, the total amount of solutes, uh remains the same. When this plasma passes through the glomerulus and becomes filtrate, its osmolarity is nearly the same as the plasma to excrete excess water. The filtrate is diluted as it passes along the tubule by reabsorbed solutes at a higher rate than water. This only occurs in certain segments, though. In the proximal tubules, solutes and water are reabsorbed in equal proportions, so little change in osmolarity occurs. Thus the filtrate remains iso osmotic as filtrate passes down to the descending loop of hennelly, water is reabsorbed by osmosis and the tubular fluid reaches equilibrium with the surrounding interstitial fluid of the renal medulla. The renal medulla is hypertonic. As I just circled here, uh, as compared to the original filtrate. Therefore, the tubular fluid becomes more concentrated as it flows into the inner medulla. In the ascending limo of the loop of Henley, especially the thick segment. Sodium potassium chloride or avidly reabsorbed. You can see this here graphically, um. However, it is impermeable to water even when Ada is present. Therefore, the tubular fluid becomes more dilute as it flows up the ascending loop of Henley. The osmolarity decreases from around 300 to 100 milliards moles per liter, regardless of his presence. Fluid leaving the distal tubular segment is hypo osmotic. You can see that here. So hyper osmotic. Uh, slightly hyper osmotic and then hypo osmotic. As the dilute fluid in the early distal tubule passes into the late distal convoluted tubule, cortical collecting ducts, and majorly collecting duct, there's reabsorption of sodium chloride. In the absence of ADHD, this portion of the tubule is also impermeable to water, and the additional reabsorption of solutes causes the tubular fluid to become even more dilute. Since water is not reabsorbed and solutes are, this leads to a large volume of dilute urine. The necklace. The mechanism for forming dilute urine is to continue reabsorption of solutes from the distal segments of the tubular system, while there's reduced water reabsorption. Fluid leaving the ascending loop of Hindley and the early distal tubule is always dilute regardless of aid levels. In the absence of Ach, the urine is further diluted in the distal tubule and collecting ducts and a large volume of urine and a dilute urine is excreted in the presence of Ach H. Though a large volume of water is reabsorbed and urine can be concentrated. Water is continuously lost from the body through these roots. Fluid intake is required to match this loss, but the kidneys have the ability to form a small volume of concentrated urine that minimizes the fluid intake that is required in order to form concentrated urine. Solutes are treated while increasing water reabsorption, which of course decreases urine volume. Human kidneys can produce a urine concentration of 1200 to 1400 milliliters, most which is 4 to 5 times the osmolarity of plasma. If the maximum urine concentrating ability is 1200 milli osmosis, the obligatory urine volume or the minimum volume of urine that must be excreted can be calculated using this formula here. In order to form concentrate urine, high levels of Aids must be present at age, increases the permeability of the distal tubules and collecting ducts to water, allowing for greater reabsorption. There is also. There also must be high osmolarity of the renal medullary interstitial fluid to provide an osmotic gradient for water absorption. The renal interstitial fluid is normally hyper osmotic, so when aid levels are high, water moves from the tubular membrane into the renal interstitium by osmosis. It is then carried back into the blood by the vasa rectum. The urine concentrating ability is limited by the levels of H and by the degree of hyper osmolality. Osmolarity of the renal medulla. The counter current multiplier mechanism is what creates the hyper osmolarity of the arena medulla. It is the special anatomical arrangement of the loops of hennelly and the vaso rectum. The osmolarity of the interstitial fluid, and most of the body is about 300 million moles per liter, which is similar to plasma osmolarity. The osmolarity. The medulla of the kidney is much higher and increases progressively to between 1200 to 1400 million moles. This means that the renal medullary interstitium accumulates solutes and greater excess of water. Once this concentration is achieved, it is maintained by the balance of inflow and outflow of solutes and water. The major factors that contribute to the buildup of solute concentration in the medulla are active transport of sodium and the Co transport of potassium chloride and other ions out of the thick portion of the ascending limb of the loop of Hindley. Uh two. Active transport of ions from the collecting ducts. Three. Facilitated diffusion of urea from the inner medullary collecting ducts into the interstitium, and for the diffusion of only small amounts of water from the medullary tubule tubules into the medullary interstitium. And we will go through this in more detail. A major reason for the high osmolarity of the loop of Henley is active transport of sodium, and the Co transport of potassium chloride and other ions from the thick ascending loop of Henley into the interstitium so thick ascending loop. Um. This pump is capable of establishing a 200 million Osmo concentration gradient. At the same time, the thick, ascending, and thin ascending limbs are virtually impermeable to water. Uh, opposite to this, the thick ascending is the, uh, descending loop of Henley, which is very permeable to water. Um, the tubular fluid osmolarity quickly equals the renal osmolarity as water diffuses out of the two below lumen and into the interstitium. Uh. So this is the, uh, descending loom here. This is the descending loom, which is very permeable to water. This is the ascending loom, which is impermeable to water and has the pump creating the concentration gradient and pumping, uh, solutes out. And this is the interstitium here in between. So now let's outline the steps in creating the hyper osmotic renal interstitium. To start with the fluid inside the renal tubule. Has a concentration of about 300 million smalls, which is the same, uh, that leaves the proximal tubule. The active ion pump in the thick ascending limb reduces the solute concentration inside the tubule and raises the interstitial concentration. So the active pump here and you can see this in step two. Um. This pump is limited to a 200ml more gradient. Uh, the tubular fluid in the descending limb quickly diffuses. So here's the descent limb. So on step three. Now, um, the two fluid in the descending limb quickly diffuses into the interstitium to create the equilibrium. Um. Then as additional fluid flows from the proximal tubule, um, it pushes this high prosthetic fluid into the ascending limb. So now this fluid that's been created been made, high osmotic is pushed around. You can see the arrow here. And for as it's pushed around the tubule, the ascending limb pumps ions out the same as we just discussed. So now it's created a greater concentration in the ascending limb. But this pump continues to pump ions out into the interstitium. Uh, and this creating that same 200 million Osmo concentration gradient. Uh, then once again, the descending limb fluid diffuses out of the descending limb. Uh, that raises the osmolarity of the dead inside the descending limb. To 500mg. Once again, fluid is pushed forward. Um, come back up here. Two steps for fluid is pushed forward, and the cycle continues. The overall net effect of this repeated process is adding more and more solutes to the renal interstitium, and increasing its osmolarity. Over time, this multiplies the concentration gradient, eventually raising the osmolarity of the interstitium to 1200 to 1400 million smalls. When the tubular fluid leaves the loop of Henley flowing in the distal convoluted tubule, the fluid is dilute with an awesome clarity of only about 100 to 140 million small. So this is in here. Uh, the early distal tubule further dilutes because it actively transports sodium out of the tubule but is impermeable to water. You can see that here. Um. As this dilute fluid flows into the cortical collecting tubule, the amount of water reabsorbed is dependent on the concentration of ADHD. In the absence of ADHD, this segment is almost impossible to water but continues to reabsorb solutes, causing further dilution. When there's a high concentration of ADHD, the cortical collecting tubule becomes highly permeable to water, where it rapidly absorbs where it is rapidly reabsorbed by the peri tubular capillaries. If you remember the period, tubular capillaries are, uh, flowing all around the loop of Henley. Uh, on page 324. There's a great image. Uh, because this water is reabsorbed in the cortex rather than the medulla. The osmolarity, the medulla is maintained as fluid continues along the major Leary collecting ducts. There's further water reabsorption, but in this area, the water reabsorbed is a relatively small amount and is rapidly carried away by the vas erector into the bloodstream. When there are high levels of Ach present and much more water is reabsorbed, the osmolarity the tubule fluid is nearly identical to the renal medulla, thus forming highly concentrated urine. Urea contributes about 50% of the osmolarity of the renal medullary interstitium. When the kidney is forming, maximally concentrated urine urea passively reabsorbed from the tubule. As water flows up the ascending loop of hennelly into the distal and cortical collecting tubules, little area is reabsorbed because these segments are impermeable to it. When at present water is reabsorbed rapidly and the urea concentration is increased in the intermediary collecting duct, urea diffuses out of the tubule and into the renal interstitial fluid. Diffusion is greatly facilitated by facilitated by the UT, A1 and UT T3 transporters, which are specific for urea. These transporters are activated by 80 H. ADHD activates these transporters, which allow for the diffusion of urea out of this tubule. Even though urea is being reabsorbed, concentrations remain high in the tubular fluid, which of course eventually forms urine, and therefore urinary excretion remains high of urea. Only small amounts of reabsorb of urea are reabsorbed in the thick limb of the loop of hennelly, the distal tubule and the cortical collecting duct, because they are less permeable to it. When aid is present. The UT, A1 and UTA three transporters cause urea to diffuse into the medulla interstitium, increasing the osmotic pressure of the renal medulla, helping to reabsorb water, which of course is the goal of ADHD, especially when ADHD levels are high when there's excess water in the body. Urine flow rate increases and urine concentration decreases, which of course decreases the interstitial osmotic gradient, causing more urine and urea to be excreted. A healthy person usually excretes 20 to 60% of the filtered urea. This is dependent upon urine flow rate and hydration. The rate of urine urea excretion is determined by these three things. The concentration of urea in the plasma, the glomerular filtration rate, and the renal tubular reabsorption. Patients with renal disease have large reductions in GFR, which increases the concentration of urea in the plasma. This then causes a higher rate to be filtered, causing the urea urea to be excreted. Despite the decreased GFR in the proximal tubule, 40 to 50% of the filtered urea is reabsorbed, although concentration in the tubular fluid remains high because urea diffuses far less than water at the same time. There are some secretion of urea into the tubular fluid in the thin loop of hennelly, and that is facilitated by the UT A2 transporter, and that is in combination. And you see this here. And of course, that's in combination with the UT, A1, UT three and uh, 80 H that we talked about on the last slide. Blood flows provided to the renal modular to supply the metabolic needs of the cells. But without a special system, this blood flow would diminish the activity of the counter current multiplier system. Therefore, there are two special features for renal medullary blood flow that are listed here. The blood flow is low, accounting for less than 5% of total total renal blood flow, and the phase of Recta serves as a counter current exchanger, minimizing the washout of solutes from the interstitial. Uh, we're going to go over that now. Blood enters and leaves the medulla via the vas recta, which is highly permeable to solutes in the blood except for plasma proteins, just like other capillaries. As the blood descends into the medulla, it becomes progressively more concentrated, partially by solutes entering and partially by the loss of water into the interstitium. By the time the blood leak, uh, reaches the tips of the base of recta, it has a concentration of 1200 milli osmosis, the same as the interstitium. As blood ascends back out of the medulla interstitium. Water moves into the capillaries, and it becomes more dilute because of this U-shape. And how the concentration in the vasa rectum mirrors the concentration of the nephron. The vas erected does not prevent the medulla osmolarity from being dissipated. The summary of changes in osmolarity and urine volume are shown in this chart. We go through the individual segments in the following slides. About 65% of most filtered electrolytes are reabsorbed in the proximal tubule. However, it is also highly permeable to water. So whenever solutes are reabsorbed, water also diffuses, and therefore the osmolarity, the fluid remains about the same as the plasma infiltrate. And you can see that here that has been circled. Um, and also here in this segment. As fluid flows down the ascending loop of Henley, water is reabsorbed into the medulla. Aquaporins one. Channels are present in this limb and it is highly permeable to water, less so to sodium and chloride. Therefore, the osmolarity gradually increases until it is around 1200 milli osmosis, and you can see that here as the osmolarity increases. Not quite a straight line, but close. Because sodium was concentrated when the water was removed in the descending limb. Passive reabsorption of sodium dilutes the fluid remaining in the tubule. The ascending limb is essentially impermeable to water but reabsorb sodium. You can see the circled segments here. The thick ascending loop of Henley is also impermeable to water, but large amounts of sodium, chloride, potassium, and other ions are actively transported out of the tubule and into the interstitial. Therefore, the fluid becomes very dilute, falling to a concentration of around 140 million moles. The early distal tubule has properties similar to the thick ascending loop. So the tubular fluid is further diluted to about 100 million moles. In the late distal tubule and cortical collecting tubules. The osmolarity of the fluid depends on the level of ADHD. With high levels, these tubes are highly permeable to water and significant amount of water is reabsorbed. Since urea cannot pass through these tubules, it results in increased concentration. In the absence of ADH, little water is reabsorbed and active reabsorption of solutes continues, further diluting the tubular fluid. The concentration of fluid in the intermediary collecting ducts depends upon ADHD and the surrounding medullary interstitium osmolarity that is established by the counter current mechanism in the presence of ADHD. Ducks are highly permeable to water, which diffuses from the tubule into the interstitium until osmotic equilibrium is reached. Since the inner medullary collecting ducts have specific urea transporters that facilitate diffusion, when urea is concentrated, it diffuses out of the tubule lumen into the interstitium, contributing to the osmolarity of the interstitial. Two important points are that the kidney can can, when needed, excrete a highly concentrated urine that contains little sodium. And secondly, large quantities of dilute urine can be excreted without excreting sodium. Lastly, there is an obligatory urine volume that is dictated by the concentrating ability of the kidneys and the amount of solutes that must be excreted. For example, if 600 million osmosis solutes must be excreted each day, this requires 2.5l of urine. Since the maximum urine concentrating ability is 1200 milliliters moles per liter. The regulation of extracellular fluid osmolarity and sodium concentration are closely linked because sodium is the most abundant extracellular ion. Sodium is normally regulated closely between 104 and 145 MQ per liter, while the osmolarity of plasma averages 300 million moles per liter. Osmolarity determines the distribution of fluid between the intracellular and extracellular compartments, and typically does not vary more than 2 to 3%. Sodium and its associated anions accounts for 94% of the solutes in the extracellular plasma, with glucose and urea accounting for the other 3 to 5%. But since urea usually permeates most cell membranes, it exerts little osmotic pressure. Molarity can roughly be estimated from plasma sodium concentration. Sodium ions in the extracellular fluid and its associated anions are the principal determinants of fluid movement across the cell membranes. Therefore, the control of sodium ion concentration and osmolarity are synonymous and can be discussed simultaneously. The two primary systems, especially involved in regulating the concentration of sodium and osmolarity of extracellular fluid are the osmo receptor system and the thirst mechanism. When osmolarity increases above normal because of water deficit, the Osmo receptor and feedback system works this way. Increases in extracellular fluid osmolarity or sodium concentration, causes osmo receptor cells in the anterior hypothalamus to shrink, which causes them to send nerve signals to additional cells in the super optic nuclei, which then sends messages down the stock to the posterior pituitary. Stimulation to the posterior pituitary causes ADHD be released from vessels in nerve endings, and enters the bloodstream and is transported to the kidneys, where it stimulates the insertion of aquaporins into the late distal tubule, cortical collecting ducts, and medullary collecting ducts. The increased water permeability causes increased water reabsorption and the excretion of small volume of concentrated urine, which causes the excretion of sodium and other solutes while conserving water, uh, correcting the high osmolarity. The opposite sequence occurs when, uh, fluid osmolarity becomes to dilute. Uh, when osmolarity is low, less ADH is formed. Water permeability is decreased in the renal tubules and less water is reabsorbed. 88 is synthesized in the super optic and pair ventricular nuclei of the hypothalamus. Both these nuclei have axonal extensions into the posterior pituitary. Uh. 80 age is synthesized and then transported down these axons to their tips in the posterior pituitary gland. When the super optic and of ventricular nuclei are stimulated by increased osmolarity, nerve impulses pass down these nerve endings, changing their permeability and allowing calcium entry. Calcium enters the nerve. Uh. Causing secretary vesicles to release ADHD. ADHD then carried away in the capillary blood to the uh, of the posterior pituitary and into the circulation. Uh. This secretion is rapid. ADHD levels can increase several fold within minutes. In addition to osmolarity causing 88 secretion releases, also stimulated by the cardiovascular reflexes that respond to decreases in blood pressure and or blood volume. This includes arterial barrier receptor reflexes and cardiopulmonary reflexes. These reflex pathways are in high and low pressure regions of the circulation. Afferent stimuli are then carried by the vagus and also pharyngeal nerves, which are then relayed to the hypothalamic nuclei. Aid release is considerably more sensitive to small changes in osmolarity than to similar percentage changes in blood volume. Plasma osmolarity changes of only a few percent are sufficient to increase ADHD levels, but ADHD levels do not change that much until blood volume is reduced by about 10%. Therefore, the daily regulation of Ada secretion during simple dehydration is affected mainly by changes in plasma osmolarity. There are some things that can cause Ada secretion. Uh, some other things that can cause Ada secretion also. And they're shown on that table here. Fluid loss is minimized by the Osmo receptor feedback system. Adequate intake, however, is necessary to counterbalance any losses that do occur through breathing, sweating, or the GI tract. This fluid intake is regulated by thirst mechanisms. Many of the same factors that stimulate Ach release also increase thirst. The thirst center is located in an anterior ventral wall, the third ventricle, and other regions, uh, and it functions as Osmo receptors in the same way that the Osmo receptors do that stimulate ADH release. The most important factors to stimulate thirst is increased extracellular fluid osmolarity. This of course causes intracellular dehydration in the thirst centers. Decreases in extracellular fluid volume and arterial pressure can also stimulate thirst by independent pathways. Another important stimuli for thirst is angiotensin two. Angiotensin two acts upon regions outside the blood brain barrier. Angiotensin two is stimulated by the factors associated with hypokalemia and low blood pressure, so its stimulation on the thirst center helps restore blood volume and pressure. Mouth and mucous membrane dryness can, uh, elicit the thirst sensation as well. And also gastrointestinal. Uh. And pharyngeal stimulation. The kidneys must continually excrete an obligatory amount of water. Even in a dehydrated person, to rid the body of excess solutes that are ingested or produced by metabolism. Water is also continually lost to evaporation due to breathing and from sweating, as well as the GI tract. The threshold for drinking is only about two emic per liter above normal osmolarity. This is when the thirst mechanism is activated, causing the desire to drink. Only. A small change in osmolarity causes a desire to drink, which of course restores osmolarity to normal. In this way, cellular fluid osmolarity is precisely controlled and healthy person. The Osmo receptor eight and thirst mechanisms work in parallel to regulate this, even with sodium intake as high as six times normal. This is only a small effect on plasma sodium concentration, as long as the aid and thirst mechanisms are functioning normally. That is what is shown in the graph here. The red line shows increased sodium intake. Uh, but cellular concentration remains the same. Um, here. And you can see increased amount of sodium intake. Uh, but plasma sodium concentration remains the same. Um. The blue line shows the effect of ADHD. If the ADHD systems are blocked, the ADHD and thirst mechanisms are blocked here with the blue line and you can see the plasma concentration increasing greatly with increased sodium intake. Even if one of the systems fail, the other can still control osmolarity with reasonable effectiveness. As long as there's enough fluid intake to balance obligatory urine volume. However, if both ADHD and thirst mechanisms fail simultaneously, sodium concentration and osmolarity will be unable to be controlled. No other feedback mechanism is capable of adequately regulating plasma sodium concentration and osmolarity.