BISC 307L 2nd Edition Lecture 39 Current LectureOn left are the responses of the body to a decrease in blood volume and blood pressure. The most common causes of this are dehydration and hemorrhage. Decreased blood volume and blood pressure will boost cardiac output and the hypothalamus will stimulate a desire to find and drink water.The kidneys play a very important role as well because they can minimize water loss through theurine. The ultimate solution to the problem is drinking and getting more water. But the kidney can at least prevent further loss of water. It is not obvious from this diagram, but there are two different types of pressure receptors, or baroreceptors, in the body. They are in the carotid body and aortic body. They are referred to as the high pressure baroreceptors. But in addition to that, there are a set of low pressure baroreceptors. They are stretch sensitive nerves in the atria, the pulmonary vasculature, andthe big veins. So these are highly compliant parts of the vascular system. And because these are low pressure, highly compliant parts, they tend to expand. So these low pressure baroreceptors are often called volume receptors. Whereas the high pressure baroreceptors are called pressure receptors. The reflexes that get activated when pressure is too high or low are one set – they overlap, but they are distinctive in other ways from the reflexes that kick in when blood volume is too high ortoo low, and these two sets of receptors is what sense those differences. Water Balance in the BodyIn order to not gain or lose water, the body has to be in water balance. You would gain 2.5 liters of water a day.Notes:1 Not including intravenous infusion2 Mostly from aerobic respiration (fuel molecules + O2 ® CO2 + H2O)3 Not including diarrhea, vomitingSo water input has to equal water output, and things need to be in balance. No matter how much water one drinks, we’ve already seen that a variable amount of plasma gets filtered into the kidneys. So way over 99% of that water has to be reclaimed. Most of that reclamation happens in the proximal tubule. A little more happens in the loop of henle and part of the distaltubule, which leaves the rest of the distal tubule and the collecting duct as the places that do the final adjustment of how much water is excreted from the body. Osmolarity Within KidneyThis is a picture of the osmolaritywithin the kidney. Can see thejuxtamedullary capillary with the longloop of henle, and as you know, thekidney has this osmotic gradient in itwhere the cortex and outer medullahave an osmolarity of about 300mOs/M, which is about the same asblood. But as you go deeper awayfrom the outer medulla, it gets moreosmotically concentrated. It gets upto 1200 at the deepest part, duemainly to high concentrations of saltand urea. The cells in here have tohave special adaptations to keepfrom being denatured by this specialsalt and special urea. In the little yellow boxes are shown the osmolarity of the tubular fluid at different strategic points along the length of the tubule. The filtrate in the bowman’s capsule of 300 has the same osmolarity of blood. And as the fluid is pushed by the net filtration pressure along the proximal tubule, it ends up along the proximal tubule still being 300. We know that water is reabsorbed, but we also know that it is done so by reabsorbing the solute and allowing the water to follow, so the osmolarity overall stays the same. So the fluid is at reduced volume. It enters the loops of henle at 300 mOsM. Keep in mind that epithelial cells in the descending loop of henle are permeable to water but not to salt. So there are aquaporin channels and leaky junctions. The ascending limb of the loop of henle is permeable to salt, but not water. So given that there is an osmotic gradient, what happens is that tubular fluid at 300 comes down, and water leaves by osmosis. And salt cannot follow. So the fluid in there gets increasingly salty. So by the bottom of the loop, the tubular fluid will be asosmotically concentrated as the surrounding interstitial fluid. The water that leaves gets reabsorbed into the vasa recta – it doesn’t just stay around and dilute the interstitial fluid. So the fluid takes the hairpin bend and starts getting pushed upward. The walls of the tubule of theascending limb are permeable, but not to water. In the thin part of the ascending loop, there are no active transporters – it is just permeable to salt. And as this salty briny fluid comes up thetubule, it is increasingly moving int o an environment where the interstitial fluid is less salty. Sothere is a gradient for salt to go out. And it does go out. And as it goes out, the tubular fluid becomes less salty. It comes into equilibrium with the interstitium around it. When you get to the thick ascending limb, it is thick there because these are big beefy cells that are packed with mitochondria. And the reason they have mitochondria is because they carry out a lot of active sodium transport. The passive movement of salt out in the thin ascending limb gets replaced with active transport of salt in the thick part. This is necessary because the concentration gradient for salt to go out gets smaller and smaller as you go up. To ensure that more salt is being absorbed, active transport takes over, and salt is actively extruded from the tubular fluid. This salt that comes out contributes to the salty inner medulla. But this is happening all day long – the excess salt getsreabsorbed back into the vasa recta.So much salt is pumped out of the thick ascendinglimb, by the time you get to the top, the osmolarityof the fluid is lower than that of body fluids. Reabsorption of Na+, K+, and Cl- in the AscendingLimbThe important organ here is the Na/K pump in thebasolateral membrane. All these ions going to theright being transported out of here are beingmoved by the Na/K pump. This transporter isunique to this part of the nephron. And it isimportant to realize that because there are drugsthat can be used to get rid of water from the body,or not, that target this transporter. So thistransporter brings one Na, one K, and 2 Cl in. Thesodium ions that come in get pumped out. Thepotassium ions go through potassium channels or potassium symports in the basolateral membrane. And the chloride goes out of chloride channel or goes out with potassium through that symporter. Notice the water cannot follow and gets left behind, so tubular fluid can become