 Hello and welcome to Physiology Open. Try to solve this question on counter-current mechanism. You can pause the video and think about the answer. We will come back to the question once again at the end of the video. Quickly let us now see the anatomy of a nephron. A nephron consists of a bowman's capsule, proximal convoluted tubule, straight part of proximal tubule, descending thin limb which enters into the medulla, then the nephron curves back and ascends in medulla, so this is ascending thin limb. In outer medulla and cortex, it continues as thick ascending limb, coming close to bowman's capsule. Just after this portion, it continues as distal convoluted tubule, then connecting tubule and collecting duct, which has a cortical portion known as cortical collecting duct and then medullary portion known as medullary collecting duct. The proximal straight tubule, descending thin limb, ascending thin limb and thick ascending limb all together are known as loop of Henle. So from here to here is loop of Henle. Kidneys need to excrete concentrated or dilute urine depending on the hydration status of the body. The concentration or dilution of urine depends on the presence of a gradient of hyperosmolarity in medullary interstitial. That means here in the medullary interstitium, fluid will be hypertonic with maximum hypertonicity present at the tip of the medulla and decreases towards the outer medulla. Basic function of counter current mechanism is to make the medullary interstitium hypertonic. So there are two aspects, generation of hypertonic gradient in medullary interstitium and maintenance of hypertonic gradient in medullary interstitium. Now generation of gradient occurs by counter current multiplier and maintenance of gradient is done by counter current exchanger. So first we will discuss the generation of the gradient that is counter current multiplier. There are three requirements for the generation of this hyperosmolar gradient. First, the flow of fluid in nephron should occur in closely parallel tubes and in opposite direction. You may notice here obviously while passing through the various segments of the loop of Henle, fluid flows in parallel and opposite direction. Second, both sides of nephron should have differential permeability. Here ascending limb of loop of Henle is permeable to solutes only and descending limb is permeable to water only. Permeability in thick ascending limb to solutes is by active transport. There is a transporter sodium potassium 2 chloride present on the apical membrane of cells of thick ascending limb which help in absorption of these ions which ultimately move to medullary interstitium via the basolateral membrane. While permeability to water in the descending limb of loop of Henle is basically passive. Water moves passively to the side of higher solute concentration via aqua 4 in 1 channels which are present on the apical membrane as well as on the basolateral membrane of thin descending limb of loop of Henle. Third thing is length of nephron. Longer than nephron, the medullary interstitium will become more hypertonic. Okay, so how is this medullary gradient generated? The fluid which filters through the Bowman's capsule has the same osmolarity as that of blood. For the purpose of understanding, we will take one value of 300 milliosmos per liter of fluid. It's a range. Now we are considering the first time as fluid passes through the nephron. So it is like everywhere the osmolarity of the fluid is same even in the medulla. This is a hypothetical condition though, right? But to understand we have to think of this hypothetical condition. So everywhere it is 300 milliosmos per liter. Now as the filter fluid of 300 milliosmos per liter osmolarity passes through the nephron. See even though it passes through the descending limb which is permeable to water, there will be no net movement of water because the osmolarity of fluid is slain everywhere. For water to move passively, there should be some gradient, right? Now as the filtrate passes through the ascending limb, the sodium potassium to chloride transporter basically it is a simporter starts throwing out these ions into the interstitium since it is active transport. Now because of this, the osmolarity of interstitium increases and osmolarity of fluid in the nephron decreases. So fluid in the nephron becomes hypotonic. Now this effect on osmolarity of medullary interstitium by passing of fluid in the nephron is known as single effect. Now let's come to second cycle. As fluid passes through the descending limb, now see because of the first cycle there is a gradient for water to move. So passive movement of water occurs from descending limb into the medullary interstitium. This will tend to dilute the osmolarity a bit of medullary interstitium and the osmolarity of tubular fluid will increase. So here in the loop of Henle at the tip of the medulla the tubular fluid will be hypotonic. Now as the hypotonic fluid of nephron passes through the ascending limb, this transporter sodium potassium to chloride will have more concentration of ions to work with. So it throws out more and more ions decreasing the osmolarity of the tubular fluid while increasing the osmolarity in medullary interstitium. See this effect is greater than the first cycle because now in second cycle these transporters are working with hypotonic fluid. But also see this effect will be more set at the beginning of the ascending limb because fluid is more hypotonic here. As fluid passes ions are moving out and the tonicity is decreasing. Transporters here have the fluid with lesser osmolarity compared to that near the tip of the medulla. So they will be able to throw lesser ions but it will also increase the osmolarity of the interstitium but not as much as near the tip of medulla. So this will create a gradient of osmolarity in medullary interstitium. So this medullary osmolarity keeps on increasing with each cycle of fluid passing. This is what? This is multiplication of the signal effect. See here in diagram of single effect single cycle of fluid passing could only increase the osmolarity of medullary interstitium to this much. But as multiple fluid cycle pass the osmolarity keeps on increasing until 1200 miliosmos per litre at the tip of the medulla. So that is why this mechanism is known as counter current multiplier. Counter current because fluid is flowing in parallel but opposite direction and multiplier because with each cycle of fluid flow multiplication of medullary osmolarity is occurring. Also see that if the length of the nephrons is more. These transporters will have more time to throw these ions since fluid will need more time to pass. So that is why counter current multiplication occurs in juxtamedullary nephrons which are much longer than cortical nephrons. Okay we have finished generation of osmolarity in medullary interstitium. Now let us see how it is maintained. Imagine a situation in which blood flows like this along a nephron. So here is a capillary which goes straight along a nephron. Now remember that capillaries are permeable to salt as well as to water. That means they can freely pass through capillaries or into the capillaries depending on the gradient. The osmolarity of the blood as we have discussed is 300 miosmoles per liter. Now so if the capillaries pass like this see due to medullary hyper osmolarity water will pass out of the capillary while salt will pass into the capillary. This is going to dilute the medullary osmolarity and in turn this is going to make the blood hyper osmolar. Oh that's not good all the job which the nephrons have done will be lost. The solution to this is simple. The capillary bends into a U shape. So see here at this end near the bend the blood would have become hyper osmolar due to all water moving out and ions coming in. But as the blood moves up it will encounter opposite gradients. So water will move into the capillaries and ions will move out and thus the osmolarity of both the medullary interstitium as well as of blood in the capillaries will be maintained. So it is the opposite direction of exchange of water and solutes which is occurring in descending and ascending limb of these blood vessels. So this blood vessel that is the basorecta acts as a counter current exchanger and helps in maintaining the gradient of medullary interstitium. So basically end result of all this is excretion of a dilute urine. See the osmolarity of the tubular fluid here in distal conglolated tubules are hyposmotic that is it is less in that of body fluids because of all of the solute absorption taking place in thick ascending limb. However to concentrate urine we need ADH. In brief about role of ADH? See ADH increases the permeability of cells to water in last part of distal tubules, collecting tubules and collecting ducts. Only if medullary interstitium is hyper osmolar water will move from nephrons into the medullary interstitium and then into the blood. And more the osmolarity more will be the water absorption. So presence of ADH in presence of hyper osmolar medullary gradient will help in concentration of the urine. Okay now let's come back to our original question. A diuretic inhibit sodium potassium to chloride transporter present on ascending limb of nephron and you have to tell which of the following statements are correct. Let's see each option one by one. See any drug which blocks sodium potassium to chloride transporter will not let the medullary interstitium hyper osmolarity to develop. So first option is correct. And if medullary hyper osmolarity is not there ADH effect will not be there because even though ADH increases the permeability of the cells to water, water will not have the gradient and will not be absorbed and urine cannot be concentrated. So second option is correct and see the fourth option it decreases kidney's ability to concentrate urine. Yeah that is also correct. Then obviously water will not be absorbed it will need to more volume of urine, right? So third option is also correct. So in this question all four options regarding that particular drug is correct. By the way drug which inhibit sodium potassium to chloride transporter is known as loop diuretic and we have discussed the various diuretics in this playlist out here you can check it out. Okay thanks for watching the video. 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