 Welcome back to the NPTEL lecture series on animal physiology. So, we are in the section of kidney and the regulation of fluid in other words in the excretory system. So, we have already done the basic structure of the smallest functional unit of kidney, the nephron. How the individual nephrons are involved in the whole filtration process. So, we have done with the structure, but a little bit of a structure is left because when I drew the structure I showed you distal tubule, proximal tubule, Bowman capsules and all those things. So, what we will do initially in our first slide, I will explain all the different cellular structures which are present at different zone at proximal border, at distal border and all other places. And then we will talk about the simple driving forces which are regulating this whole process. And then we will talk about the counter current multiplier and we will close in with the renin angiotensin system which is regulating the fluid. So, even before I start with the cellular structure, let us have a simple understanding exactly what is happening. The way it works is fairly straightforward if you look at logically. So, the blood which is coming, so blood is not in physical contact, not in connection with the nephrons. So, basically here is the blood vessel which is entering and here you have the nephron, if you go back to the structure you will look at it. So, there is a gap between the two, fine. So, say for example, this blood vessel is carrying something say molecule X whose concentration is higher and whereas, the concentration of the molecule X in this vessel in the nephron is lower. So, automatically from the higher concentration we will move on to the zone of lower concentration. So, one of the forces which promotes this whole process is osmotic pressure. And the second force you have to realize there is another force which is governing here that is the hydrostatic pressure. The amount of water which is present on these blood vessels and the amount of water which is present out on the other side in the nephron because it is the water which is carrying the ions. It is not that single and just the ions will move out. So, whenever the ions are moving along with them they are pulling a stream of water with them. So, hydrostatic pressure and osmotic pressure we will talk about it and we will talk about one of the very interesting mechanism called counter current multiplier which is fairly common in biological systems. But we will just you know kind of go through it and I will expect you guys to consult other advanced textbook to know more about it. So, let us continue and let us talk about the different cellular structures which are present in the proximal and distal tubule of the nephron. So, coming back to the slides. So, basically in the proximal tubule cells are like this proximal tubule cell. So, these individual cells have a lot of brush borders like this. These are the brush border your two brush if you look at it is almost like this. So, this is the brush border which is increasing its surface area of contact and here it is. This is the basal part of it structures like this all over the place. So, this is how the proximal tubule cells look like which forms the proximal tubule of the kidney and these structures are nothing, but mitochondria lot of mitochondria there is lot of energy dependent processes are happening and underneath underneath you have the basal lateral labyrinth basal lateral labyrinth basal lateral labyrinth brush borders. So, this is all about the structure of the proximal tubule from here we will move on to the structure of the distal tubule cells depending on their functions their anatomy changes distal tubule cells. So, the distal tubule cells are something like this this basic structure remains the same you have the mitochondria likewise, but this torque difference comes somewhere else. So, they hardly have any brush borders. So, there are no brush borders you have the of course, the mitochondria sitting here like this all along the place and you have the basal membrane. So, these are the empty stands for mitochondria and these cells are without the brush border and then there is a third kind of cells which are present in the loop of Henley cells. So, these loop of Henley cells are something like this which is totally different from the distal and the proximal cells. So, after looking at these cells we are able to appreciate that how a different part of the whole nephron the cellular architecture changes you cannot if there is no uniform cellular architecture and cellular architecture changes based on the requirement of that particular part where what is happening. So, now I will just draw another cellular structure to show the epithelial cell lining between the glomerular into the Bowman capsule and the blood vessel how they are doing. So, coming back to the slides let us draw the glomerular membrane essentially this glomerular membrane is something like this it is kind of a perforated structure out here what I am trying to draw. So, on this side. So, you have the blood on this side and the glomerular filtrate on the other side filtrate. So, what is happening essentially is these are the RBCs which are there you have the plasma proteins on them. So, RBCs just putting Pp as a plasma protein. So, this is the endothelium lining of the blood vessel thelium lining of the blood vessel and these are the fenestrated capillaries if you remember fenestrate or the windows and on this side and these are the this slit force are kind of like this fully continuous there are certain barricades out there and this side you have the epithelial lining of the glomerular filtrate glomerular membrane called the slit force and essentially what is happening is these fluids are moving like this may be in an energy dependent manner may be in an independent manner likewise. So, this is how the movement of the fluids are taking place from the blood vessel to the glomerular membrane. So, there is in essentially what you do you put a physical mesh around and through the mesh things are moving though they are in physical contact, but they too are different entities like one hand and this hand they are two separate entities, but in this junction what I what I was trying to draw the previous slide was in this junction all the movement of the fluid along with the solutes is taking place. So, and this is a very common thing all across the biology where you see two individual entities. So, there is no nothing like a gap junction or something it is there are small pores and those pores are regulatory pores they are not just physical pores that anything can pass through this diffusion what I just now highlighted could be energy dependent diffusion energy independent diffusion protein carrier mediated diffusion we will talk about all those things how these transport is taking place, but this is a simple transport phenomenon it either name either may need energy or may be independent of energy requirements. Now, from here I will move on to the next which is the Baumann capsule back to the slide. So, so talking about the Baumann's capsule. So, Baumann's capsule is something like this. So, the Baumann capsule is if this side is showing the membrane and this side you have. So, the blood vessels. So, the blood vessels are coming like this they are entering like this and there is a lot of networking of the blood vessels they are almost you know comes out like this. So, back. So, this is your this is the arterial blood entering or the afferent arterial arterial arterial blood and you have the glomerulus membrane here essentially coming out is the second this is the glomerular filtrate and this is you have the Baumann capsule here you have the Baumann capsule these are afferent arterial glomerulus and this is the glomerular filtrate. So, after this basic understanding of the structure I will move on to the next part which is the forces which are driving this whole filtration. So, as I was mentioning just in the beginning of the lecture there are two major forces hydrostatic forces and osmotic forces. So, let us look at it and let us enumerate all of them and let us see the relation between them. So, what are the factors determining the filtration. So, the two major factors which are. So, this is also a very important factor called GFR this is regulated by two forces one is the hydrostatic force and hydrostatic force is essentially between the capillaries and here you have the is nephron so nephron vessel individual nephron. So, the hydrostatic force something like this represent by an arrow and you have the next force which is the osmotic pressure you can also call it hydrostatic pressure or force or osmotic force or osmotic pressure. So, the relation stands like this GFR is equal to k is the constant c s e i I will just explain what is that i c minus pi i where c stands for capillaries p stands for hydrostatic pressure this p also stands for hydrostatic i stands for Bowman capsule this i also stands for that and this c stands for capillaries and this pi stands for osmotic pressure. So, the difference between hydrostatic pressure and the osmotic pressure is considered as the lomerular filtration rate. So, this is how at different zone the filtration process is being executed while the fluid is moving through it and whatsoever fluid initially moves at the Bowman capsule is being absorbed reabsorbed and secreted and likewise it goes through a whole channel. And the whole idea is to retain as much water as possible and not to lose the electrolytes. So, electrolytes have to be retained and in that process getting rid of the urea and uric acid and all other unwanted molecules which could de-stabilizes our homeostasis of the body. So, from here we will move on to. So, just coming back to the slides let us get back to the slides and so after this we will just move on to the next part of it which is we will talk about how the sodium is getting absorbed at different zone. So, how about this? So, we take an individual case of an individual nephron and we divided it to two parts three parts the cortical region the cortex outer medulla and the inner medulla. So, this is the cortex this is outer medulla O stands for outer and I stands for inner medulla draw the nephron now. So, the nephron is like you know out here it starts and moving through this is the distrality view and it is all the way moving down down down and then again it is becomes thicker thicker and then twice and here the urea is getting formed. So, if you look at it so this is the zone where it is much more thicker this is the thicker segment which is then it becomes thinner this continues to be thinner and then again it becomes thicker here this is how it goes. So, now what is essentially happening is this. So, this is how we just much more clear here the blood vessels are entering here. So, basically what we will be talking here is about the sodium resorption in the nephron this is one of the major molecule which you have to ensure that it is regulated right. So, the first thing which is happening so sodium is entering through this here the sodium is coming in this is all in the blood. So, from the blood the sodium molecule. So, if I represent the sodium molecules now let me represent the sodium molecule by say I use for example, I use uro color these are the sodium molecules So, these sodium molecules then first move here these yellow colors are the sodium molecules. So, they are they are traveling down fine concentrated concentrated out here. So, at this point somewhere out here in the cortex part of the sodium is being using a energy driven process part of the sodium is being reabsorbed. So, here it is getting reabsorbed fine. So, then again sodium is moving through moving through moving through moving through out here and if you look at the osmolarity valve value of the sodium you will see at this zone this is 290. So, the value went down further. So, this is 100 percent which has moved out here then it is 290 and then out here sodium is moving all the way all the way through the loop of Henley and out here again at this zone. Second level of sodium absorption is taking place and this is again an energy driven process. So, this is an energy driven process again sodium is getting out and again sodium is moving all along this sorry all along this all along this tubule and out here this part of the circuit is very important. So, I will highlight it with another color just to tell you like this is the zone which is under the control of the aldosterone this is the zone purely under the aldosterone control and the third level of sodium absorption takes place at this point out here out here the third level of energy dependent sodium absorption is taking place the last level where sodium is being again retained by the system and osmolarity values of sodium keeps on changing from 290 it becomes around 600 here the maximum is here 1200 and then out here it becomes 220 and likewise it keeps on changing and at this zone this zone is called this is the zone where this is the zone the shearing zone what I am doing with the sheet. Now this is called this part is called isotonic resorption. So, this is how the sodium so if you look at it the most simplest of all the sodium is kind of reabsorbed in a very interesting manner as it is moving through and all the time it is the two driving forces which are playing critical role hydrostatic force hydrostatic pressure and the osmotic pressure these are the two key players which are regulating this whole process very tightly from here we will move on to something called counter current multiplier what is because if you realize these tubes are in close proximity. So, if I am drawing this thing with a lot of space but in real life they are fairly close this is tubes look of only moving. So, what is counter current multiplier? So, counter current multiplier is say for example, you have two tubes fine two tubes like that let me let me draw it actually that will make more sense. So, let us move on to counter current multiplier. So, what essentially is counter current multiplier? So, let us think of two tubes here. So, one tube is like this and there is another tube which is like this fine they are in touch but they are not continuous with each other another word. Now, think of a situation I so from here fluid is moving or water is moving at 0 degree centigrade and from here water is moving at 100 degree centigrade by the time. So, automatically the one which is moving 100 degree centigrade will dissipate its heat to this side if there is a conduct there is a possibility of a conduction if they are not very well insulated. So, essentially what will happen the water which will come out of it is 50 degree here 50 degree here. In other word what has happened the water which has moved at 0 degree has gained heat out here and the water which has moved at 100 degree has dissipated heat out here and reduce its temperature. Now, think of a reverse situation. So, this is a simple exchange this is a very simple exchange of there are two tubes which are moving parallel. Now, think of a reverse situation. So, let us talk about the reverse situation now reverse is here is one tube which is moving through the sticker fine and there is another tube on the side which is in yellow like this. Now, we are reversing the case of the direction of flow what we are doing essentially is from this side water is moving at 0 degree and from this side water is moving at or rather sorry from the reverse side water is moving at 100 degree. Now, what will happen this is moved at 100 degree and sorry 100 degree centigrade. So, what essentially happens is that. So, while water is entering it is at 100 degree centigrade and here water is moving it is at 0 degree centigrade from the point it is started touching each other. So, up to this it is fine up to this it is fine all moving from here on situation will be something like this will be at 80 this will be at 70 this will be at say 60 this will be at 50 this will be at 30 this will be at 20 end of it this will come out as 10 degree and this will come out as 90 degree. So, this is the phenomena where the fluid is flowing in two reverse direction with different parameters makes change the energy in a different way and that is what is called a counter current mechanism. And this counter current mechanism is fairly common in biology and one of the classic case of counter current mechanism which is being followed in the kidney is in the loop of Henry. And now I will show how basically this counter current multiplier actually it is called counter current multiplier helps in concentrating sodium and other ions in the reabsorption and absorption processes. So, what we will do we will consider these two tubes now and we will see. So, this is basically a loop of Henry like this and we will observe how with respect to the interstitial fluid because here you have the interstitial fluid you have the kidney. The loop of Henry which is moving. So, if there are two arms of the loop of Henry something like let me draw it here you have the two arms which are moving like this very close proximity and you have the interstitial fluid in between. So, this whole part is interstitial fluid which has a different kind of osmolarity values. Now, what will happen now here the redraw this part now water moving. So, this is the counter current loop counter current loop of water and values which are being shown at the osmolarity values. So, out here you have 600 osmolarity 600 800 and 1000 osmolarity 1200 1000 800 600 what is essentially happening is that and this is all water molecules outside it is 600 and from this it is 600 this side also it is 600 then here you have 800 and you have 1000 and same way from the surrounding 1000 800. So, this is the counter current loop. So, this is the counter current loop which is taking place here they will try to balance each other on either side. So, on both side it is balancing. So, now if you see the how the counter current multiplier works counter current multiplier works like this as of now we have introduced any the counter current mechanism I never introduce any active transport of anything. So, say for example, it is entering at 400 osmolarity value. So, water. So, here what is happening it becomes 600 it is getting more concentrated then it becomes 800 it is getting even more concentrated then it becomes 1000 osmolarity value the bottom it becomes 1200 then it again becomes 800 then it becomes 600 then it becomes 400 and it becomes 200 and likewise. So, what essentially happened at this point. So, these are the zones if you remember I was telling you that they are at energy dependent mechanisms which are governing several things out here. So, coming to those energy driven mechanism. So, what is happening here is NaCl is being thrown out by an energy driven process. So, when NaCl is being thrown out. So, what essentially happened in that process is 1000 here 1000 1000 on this side because there is nothing is being thrown out on this side 800 100 600 400. So, what let me just finish this drawing. So, that. So, it started with 400 and then it landed up with 200 it is reducing. So, what is happening. So, and here it is basically milli osmol per kilogram of water and here you have 1200. So, in the counter current multiplier what essentially is happening. So, for example, the water is entering with a different osmolarity, but if you would have been a regular counter current mechanism which was which I just showed you before this. This is a this is a regular case where there are no active transport which is taking place. So, you see 800 here 800 here 800 here 800 here, but think of a situation where in out here where you have these these transporters which are sitting here this one this one this one. So, they are continuously regulating or modulating or manipulating the solute concentration. So, if you look at it out here here it started with 400 ended up with 200. So, there is basically a fall in the osmolarity value and sodium has been retained. Similarly, if you like look at it in this zone it is all the same because there are no transporters as soon as this transporters comes into play the things it starts changing. So, this is where the counter current multiplier is one of the mechanism by which kidney ensures that we retain as much fluid as possible. So, from here what I will do I will move on to the aldosterone the role of aldosterone what it is doing in the kidney in concentrating the urine and then we will talk about the renin angiotensin and closing that. So, coming back to the role of aldosterone. So, say for example, you have a situation when there is a water deficit you are in the desert or some kind of a situation water deficit situation. And so, plasma osmolarity will be going up because your water is shortage and your atrial pressure is also go up under these situations what will happen your antidiuretic hormone ADH will be secreted and that will activate the thirst area and this ADH which is secreted will tell the kidney. So, here in the kidney an ADH is secreted up in the pituitary it will tell kidney for water resorption this will go up maximum water reabsorption and urine goes down. So, anti diuresis. So, this is how from the brain this is being controlled and now think of another situation when there is a water excess. So, under water excess what will happen the same thing atrial pressure AP that is going to go down sorry atrial pressure. So, I made a mistake kind of corrected. So, initially what is happening atrial pressure here is going down and atrial pressure here is going up and your plasma osmolarity plasma osmolarity is basically going down and that situation there will not be any further secretion of ADH and there will not be any signal. So, what will happen water resorption will fall down your urine secretion will go up. So, this is what is happening with aldosterone root is the second thing what will happen in the salt excess and salt deficit. So, if for example, somebody is fasting. So, there is an deficit or somebody is eating too much salty food. So, there is a salt excess. So, the salt excess is there. So, automatically your plasma volume will go up to go up because it will retain more and more water. Once the plasma volume goes up it inhibits the secretion of renin which is present on top of the kidney out here. So, the renin is secretion. So, sodium resorption goes down. So, you do not need because you already have excess salt out there. So, you do not really need to activate anything, but think of a situation when there is a salt deficit. This is what happens in fasting salt sorry salt deficit. Under a salt deficit situation your plasma volume is going to go down and this will lead to the secretion of renin. So, what renin will do essentially renin will activate something called angiotensin and this angiotensin will secret aldosterone. Aldosterone will essentially will just do the reverse thing. Sodium reabsorption will be will be increased and salt excretion will be reduced. Salt reabsorption will be reduced and if you look at it in slightly more a what exactly happened when there is a renin release. When there is a renin release renin essentially breaks down angiotensin. After breaking angiotensin it form something called angiotensin 1 and angiotensin 1 then transform into angiotensin 2. It is this angiotensin 2 which has multiple function. This is basically appetite for salt is increased your thirst is increased your global lower filtration rate is being reduced. Your aldosterone secretion further lead to salt and water retention and ensuring that there is no further loss in this whole process. So, what we essentially see here is that while from the Baumann capsule the fluid moves to the nephron that fluid has to be processed very very tightly. You cannot afford to lose too much of sodium too much of water you have to retain as much as water is possible. As well as the electrolyte all the other electrolytes and you have to ensure that you lose urea and other unwanted materials. So, there is this counter current mechanism which is coming into play. There is this osmotic pressure there is this hydrostatic pressure and then we talked about this is these are being controlled by the higher centers of the ring. So, that brings us to an end of this part of kidney and the regulation of fluid. Thanks a lot.