Functions of Kidneys | Physiology and Structure | Dr Najeeb

Today, we are starting with the renal system. Right. First, we'll start with the renal physiology, and once we have done a good understanding of the renal physiology, we'll build over that the disturbance of linear function, that is renal pathology. Internal physiology means that how the renal system functions normally, and when the system of the original system is disturbed in its function and structure, we say this is renal pathology. And after that, we'll go to the renal pharmacology.

So before we really delve into details of the renal system, I will discuss a very, very basic concept. Later on, of course, we're going to very big detail, how the nephron works, how every part of the method works, but first of all, we'll talk, we'll start our lecture with the very basic, right? Number one: What are the functions of the renal system? Functions of the renal system. This is the first aspect which we will cover first of all, right. And the second aspect I will, I would love to cover is that hormones and kidneys. Hormones and kidneys. After that, I will go really into detail how the nephrons handle different substances, right, during urine formation. So what are the normal functions of the kidney? Yes, please. Okay, we start like this: that kidney can do number one, it has some excretory functions, right? There are excretory functions. Everyone knows, even a small child knows, and Mama and Papa tell the urine is coming from the kidney, right? At it eliminates the waste product.

Number two, the renal system is concerned with regulatory functions. We'll talk about what are those regulatory functions. Regulatory, regulatory functions, right? There are excretory functions; there are some substances which are excreted through the kidney, the waste products. We'll talk into detail. Then the other substances which are regulated, the balance is regulated in the body by the forgiveness. Then there are endocrine functions of the kidney. Kidneys are endocrine organs as well. So endocrine functions, and of course, at the end, we'll come to the last, most important function. I don't know somehow doctors or students don't remember that, and that is the metabolic functions of the kidney. It's a metabolic organ as well. Metabolic functions of the kidney. It means that kidneys are excretory organs; they are regulatory organs for certain substances in the blood; their endocrine organs as well as metabolically active, of course. So first, we'll go into detail that what are the substances which are excreted through the kidney, right? What are the substances which are excreted through the kidney? In the next section, we'll discuss about the hormones. First of all, kidneys, kidneys are supposed to split the metabolic waste products like urea and creatinine. So the first thing is metabolic waste products. What is the second function of the kidney? The second excretory function is, of course, when you are taking food, lot of metabolism is going on, and during those metabolic functions, some waste products are produced, and many of these waste products go through urine. At the top, you must remember urea and creatinine, is that right? Here, when we talk about metabolic waste products, and I've mentioned that there is urea and creatinine are checked into urine to see the renal function. You know this, that if your renal function is disturbed, then in the blood urine creatinine level may be disturbed. You know it? That's great. I want to know out of these two, for example, a patient comes to you and his renal function is already known that linear function of the patient is disturbed. You would love to do a serum urea level and serum creatinine level. But if you have to do one test, not both tests, which test is the gold standard for renal function? Written in… What about you, Julia? Okay, Shirin thinks that it's creatinine. Boston Celia, you are with whom? You are with Julia? What about Wakas? You are also urea man, urea. So what we decide that majority is not always right, is right. The gold standard for the renal function is creatinine. Write it down and put a star with it. If you really want to know why urea is wrong, I can explain that, or you are not interested in explanation now. You are already very much sad. Okay, let me tell you, it's important to tell actually the creatinine level in blood is mainly dependent on renal function. If kidneys are not doing working well, GFR is not there, filtration is not there, creatinine starts going up, of course, with that urea also goes up. But Julia has a problem: the urea level goes up not only in the renal dysfunction, but urea level goes up even many other conditions. For example, if you develop, you undergo sphere, or you can say too much sweating, right, and you dehydrate, then what will happen? Everything in the blood will concentrate, and urea is specifically concentrate. So urea level may go up not only in renal failure; urea level may also go up when you have severe dehydration, whatever the cause, or your sphere, vomiting, your sphere, diarrhea, right, or you have polyurea, you are losing water out of the body. Vomiting, you lose the water; in diarrhea, you may lose a lot of water; in polyurea, you lose the water; and or excessive sweating. Under all these circumstances when you're losing a heavy amount of water out of the body, you are rapidly concentrate those are right. So UDF may be high when kidney may not be so much disturbed simply by dehydration. Then another thing you know, urea is a breakdown product coming from amino acids. Everyone knows it, right? If one day you go to a special party and there's a competition who eats more chicken and who eats more beef and who eats more mutton, and maybe Mr. Vakash Sidhu, he wins the wins in the party, he hits everyone's mutton and he becomes the champion, but after a few hours, urea level in the blood will go high because he has taken too much proteins, so a lot of amino acids are breaking down and urea level will go up. I hope his kidneys will be still okay. You get me? So the point which I want to put in your mind is that when you go to the, you have to, you know, correlate the basics of the clinical that when we are talking about urea and creatinine, usually when kidney fails, both go up, but urea may go up in the blood even in those conditions when kidney is functioning okay, like high protein diet, like dehydration, right, and there are some other conditions also. So urea is not the gold standard for renal functional impairment, so renal failure; the gold standard is creatinine. Is it clear?

Okay, so we were talking about that kidneys involved in some excretory functions, and in this excretory functions, most important is that kidney should get out of the body all the metabolic, most of the metabolic waste products. Then any other substance which is excreted out of through urine? Do you know any other substance? Yes, Dr. Naznin, any other substance you can imagine in your life up to now, you've studied a lot of medicine, that some substances are going out through the urine? Yes. Okay, he's a great man; he says water goes out of the body. Listen, don't write it first. We agree water goes out, but the reason is that water is not usually a scratchy product; actually, kidney gets rid of the water while regulating the water balance. If there's less water in the body, kidney will conserve the water; if there is excessive water intake, kidney will flush out the water. So more appropriately, uh, it should be regulatory function of fluid balance in the body, your understanding. So we'll discuss that here. So I'm talking about truly waste products which we don't want to accumulate in the body. Why don't you tell me, please? Why don't you tell me something very important, like drugs? Do you think all your life you have taken so many drugs, all are stuck in your body? No, they go out of your body, right? Either they go through fecal root or they go through urinary root. So you have to remember that renal system is extremely important in getting rid of drugs. Many drugs, otherwise, you know, you have been taking aspirin and so many drugs you have taken from your childhood up to now, maybe this, this man, a bus, you will become just a bag of the tablets, but thank God not, because you keep on taking the drugs. Drugs are altered in the body; usually alteration of the drug is called biotransformation. So drugs undergo biotransformation, and they become more water-soluble, and then they go out of the body, right? So other, do you know that drug metabolites which will go out through urine? Of course, there should be water-soluble; there should be water-soluble here. There's an interesting situation that anything which has to go out of the body through the kidney, it must be water-soluble. Anything which has to go out of the body through the kidney, it should be water-soluble, right? Who is having the real idea that you know? Okay, let me tell you something interesting. I'll make a small diagram, and Mr. Sean will highlight this. Suppose this is your… Okay, I will make this diagram on this side. Let's suppose that here is your GIT, right? Here is your liver. I'm going to tell you how kidney handles along with the liver and other circulatory system, your… and this is the nephron. You know, kidney has a lot of tubes; these specialized tubes are called… I will… these specialized tubes which are present in the kidney, they are called nephrons. Nephrons, right? How many nephrons you have in your kidney, Dr. Nazanin? You know, never a sit and count it. Okay, what about you, Shrin? How many nephrons you have in one kidney? In one kidney? Yes, this is a very important concept because the whole renal physiology… look, no, when you say digital converter tubule, proximal convoluted tubules, you are talking about, about the parts of the nephron. You get it? Nephron is an epithelial tube. I will discuss into detail later, but whole renal physiology is mostly about the functions of nephron, how the nephrons work. So good strong should know at least some idea. There are how many nephrons we have in one kidney? Yes, please. You know idea? Yes. Oh, he knows that he's a millionaire as far as the nephrons are concerned. Yes, we have about 1.1 million nephrons in one kidney. So you can say 2 to 2.5 million nephrons you have working in both healthy kidneys, is that right? I've just drawn one nephron. Nephron is made of what substance? It is made of connective tissue cells, or it is made of epithelial cells, or it is made of what type of cells? It's a tube which is made of a lot of epithelial cells. This is a tube which is made of epithelial cells, and lateral lectures we'll go into detail of different parts of the nephron and how epithelium modifies along the different part of nephrons. For a while, you just trust me that nephron is just made of epithelial cells, is that right? And even this is also having epithelial cells. This is Bowman space, right? This is the filtration unit. Now, what really happens that most of the drugs which come into your body, let's suppose this is a liver cell, this is a liver cell. Mostly what happened that you have taken a drug orally, and this drug is highly lipid-soluble. You have taken a drug or a substance orally, and this is highly lipid-soluble. Because it is lipid-soluble, it will dissolve into mucosal membranes, and it will go to the through the portal circulation. It will pass through the liver, and then it will go to the general circulation. Now, this is lipid-soluble drug coming into your blood. Now, the point which I want to put that lipid-soluble substances can cross biological membranes. Lipid-soluble substances can cross biological membranes. What are the biological membranes like? GIT mucosal membrane, like blood-vein barrier, blood-brain barrier, like placental barrier. These are different examples of biological membranes. Substance which is highly lipid-soluble, that will easily absorb from the GIT and go to your circulation. Now you imagine that let's suppose this substance was supposed to work on these cells. Every drug has to work on certain areas. Let's suppose the substance was supposed to function of these cells and bring some biological changes in the body. Now, the point which I want to highlight now that how this substance can go out of the body once it is entered. How it can go out of the body, right? This is the liver, and here is your… suppose I make two hepatocytes, right? And here is your… what is this system? Suppose building drainage systems. You know, bile system drains into… is that right? Now listen carefully. This substance, again, the substance has gone into the body, right? And it is performing its function on the target tissue, is that right? Now, this substance should stay forever in your body or should go out of your body? It should go out. We do not want drugs to stay forever in our body. Now, we want it to go out. If it remains lipid-soluble… now listen carefully. One way is it can go out through the liver; other ways it can go out through… is that right? Let's see if this is lipid-soluble, it enters into liver cells, and if liver cells, by special pumps, the flowers help push this drug into the biliary system, so that it should go out through bile. You know it will never go out because it is highly lipid-soluble. Again, from here, it will come out, come back. You understand it because the drug was highly lipid-soluble. Even if from hepatocytes shift to the biliary drainage system through the bile, it will come to the GIT, of course, leave one of the GIT, but because it is lipid-soluble, it will again absorb from the GIT mucus and back to the body. So do you think the highly lipid-soluble drug can, can we get rid of them through this hepato-biliary system? We cannot. Now we'll try other routes. What is the other route? Okay, the drug is here. Now it is again highly lipid-soluble. So if it is highly lipid-soluble, you know, epithelial membranes are epithelial cells have the membranes made of lipids, lipid bilayer. You remember every cell has a lipid bilayer. So epithelial cells are also having lipid bilayer. If this is highly lipid-soluble, it will dissolve into membranes of epithelial cells and again go back to the body. So as it is passing forward, it will come back to the body because it is a lipid-soluble. So it can dissolve into epithelial cells membrane and come back to the body. Do you think then it has to go down into urine? No. What is the principle I am trying to highlight? When drugs, drugs or hormones or any substance which has, which is present in your body, if it is highly lipid-soluble, we cannot get it out through more two most effective systems. The two basic, two basic of most effective system will fail: one is the hepato-biliary system, other is the renal system. How we can really get the substance out of the body? One of the best ways: convert this lipid-soluble substance into water-soluble. Now, Vakash will tell us how we can convert a lipid-soluble substance into water-soluble substance. For example, this is a lipid-soluble substance, and here now it is water-soluble substance. How is this lipid-soluble substance converted into water-soluble substance? What is the method? Anyone who knows? Have you ever studied pharmacology? Something called pharmacology? Yeah, we keep on learning about the drugs, how they go out of the body. They metabolized… This is a very, very basic principle. And drink more water! Hey, what? Excellent! You know the one… there are two ways to convert lipid-soluble substance into water-soluble: simply this is lipid-soluble substance, and you add to it highly charged molecule. Let's suppose this molecule is highly charged. Name of this molecule is suppose glucuronic acid. It's the derivative of glucose. Many hepatocytes produce… you know, hepatocytes can produce glucuronic acid, and this is glucuronic acid is highly charged molecule, and this highly charged or polar cap you can attach with lipid-soluble, and now this complex… okay, it will become sad now, right? It is having a highly glucuronic acid or any other substance. It is now fused with any substance in the hepatocyte, and with the substance is highly charged, and so this new complex is highly polar because this new complex is highly polar, so it becomes water-soluble. The such reactions are called conjugation reactions because one molecule is conjugated with the other molecule. Have you heard of it? Conjugation reactions, and the drugs, they mentioned this drug or toxin undergoes conjugation reaction. It may conjugate with the glucuronic acid; it may conjugate the sulfates and many other products, is that right? So it becomes water-soluble. This is one way. Another way is also… another way to convert lipid-soluble substance into water-soluble is that from the substance you bring out some highly polar group. This was the tongue of the molecule, and it was previously hiding. If the tongue is highly charged, it brings its tongue out. What I mean by this that you are having… this is a drug. This drug has this component which is highly charged, but normally it is hiding in, in its structure, so it looks like lipid-soluble, but when this drug passes through the liver, hepatocytes exposes charged molecule component, and when this charge component is exposed, this becomes water-soluble. Or in this example, until its tongue is in… tongue is one of the special group of chemical group related with this molecule. Until that tongue is in, or that highly polar chain is n… this is lipid-soluble, but when it passes through the liver, it converts into more polar compound. This is another way. This is another way that this converted to more polar compound, not by addition of something new, but simply by exposing its own polar… generate. This is how substances get polar. Now, if a substance gets polar… look here, I make this that now suppose this substance has is polar. This was lipid-soluble substance; this was lipid-soluble substance, right? And this lipid-soluble substance has been converted in the hepatocytes into a polar compound. These processes are called… what are the name of such processes? Biotransformation. Transformation in the molecules within the biological system, changes in the molecule within the biological system. So what are these called? Biotransformation reaction. Have you heard of them? Then it tells you something interesting. In… you have heard that the biotransformation one reaction and their biotransformation two reactions. Heard of it? In biotransformation one reaction, right? Molecule is forced to express some inner, inner child group, or it is modified to express charge group. This is biotransformation one reaction. This is biotransformation, biotransformation type one reaction. But when you lipid-soluble substances are added or conjugated with another highly polar molecule, these are called biotransformation two reactions. This is a very basic Pharma… the biotransformation one reactions. First of all, what a biotransformation reactions? Biotransformation reactions are very simple reactions, ah, which alter the molecular structures within the biological system, right? In the liver, most of the drugs pass through biotransformation one or biotransformation two reactions. When in the liver drugs are passing through biotransformation one reaction, they expose more polar molecules; they're modified in such a way, right? But when in the liver drugs are passing through biotransformation type two reactions, they are conjugated with more polar compound. And a very interesting news: many drugs pass first through biotransformation one reaction and then sequentially the pass through biotransformation two reactions. First, molecule brings the child tongue out, and then you put the cap which is highly charged, and it becomes super polar, water-soluble compound. It's a very basic thing we should learn in the very first lecture of Pharma, how the body is dealing, how body is going to get rid of the drugs. They are not there to be accumulated forever, right? Now, this molecule is what? Polar compound. Now, our lipid-soluble substance has been converted into a polar compound. Because it has been converted into a polar compound, now it is the discretion of hepatocyte that this can… this polar compound can go out of hepatocyte easily? No, because of hepatocytes are again made of lipid membranes. So within the hepatocyte, even lipid compound convert into polar compounds, these polar compounds are trapped within the hepatocytes. Now, where they will go? Will they go to the blood? Suppose this is circulatory system. On one face of hepatocyte, we have blood; on other phase of hepatocyte, we have bile. Now it is the pure discretion of hepatocytes that some substances hepatocyte throw into actively because they cannot dissolve into membrane. Now, hepatocytes will need active transporter; they will need special transporter and transport this substance may be into the bile, or in some other examples it will use some other type of transporter and pump this substance because this is trapped; it will not diffuse out easily. So pump the substance into circulation. So these are the hepatocyte membranes which decide that once a compound… you could not understand it. Let me tell you what is happening. Let's focus this area especially. What is happening that this was a lipid-soluble molecule by biotransformation reaction which has been converted into water-soluble molecule. This water-soluble molecule is no more lipid-soluble, so it cannot dissolve, diffuse through the membranes of hepatocyte. So such molecules which are biotransformed into more polar compounds and water-soluble compounds, they are trapped within the hepatocytes. Now, it is up to hepatocytes… hepatocytes on one side have bile running boundary system.

Running on other side, hepatocytes have sinusitis running, which are the blood system. Running is that right now from the hepatocyte. Here is the Builder system and here is the blood system. Now it's up to me that difference of some substances I actively transport and to build a system, and other substances I actively transport into blood system. And still some other substances I actively transport into both systems. Now it depends on that if the substance is actively transported into Builder system, this highly charred molecule, it will come down. And when this will come down into this area, do you think this highly charged molecule can dissolve into? Now, so only destination is flash system, is it right? Because it cannot reaps up from mucosal membrane, so we got rid of this compound out of the body, is that right? This is one thing.

Second thing is if it, it has opted F5, has opted to throw this compound into circulatory system, then what happens? This uh compound from the circulatory system will easily filter into, okay, not you can say nephron. Now let's be more technical, this substance will filter into nephron. But once it filter into nephron, do you think the substance can dissolve into these lipid membranes of the epithelial cells? It cannot. So where the, where is the only destination? Urine. I think urine comes out of kidney these days, right? So what I'm talking about that this is how we can get the substances out through fecal root or substances out through urinary road.

Now I will brief all of it because it's a very very important concept. You must have studied in physiology lot of hormones. If someone asks you hormones, once they are produced, are they there in the body forever? No. For example, you become angry, I mean a friend should adrenaline short, they are from, do you think there have been a friend should remain in your blood High forever? No, where it goes, it bio transforms into more lipid highly charged molecules. Then most of the biotransferring products of epinephrine, they go through urine, is that right? So if you have studied Endocrinology, it must be clear to you that how these hormones which are produced in the body go out of the body again. All of those compounds are converted into water, water soluble system, right? In the same way, all the drugs you take, if they're going out of the body with few exceptions like some gases go out through the lungs, like in aesthetic gases, but most of them either go through the fecal root or they go out through your energy root, or a fecal root is usually called hepato Delray Road, is that right? That is called hepato Delray road.

Now another question which is there, let's go back toward. In the same way, why lever is busy in this sense? Pharmaceutical companies were not there one million years back, am I right? There were no many drugs, so-called drugs which we have now. So what liver was supposed to do then? Excellent, because you know lower animals they keep on eating anything, they don't realize. You have seen cow, does it sterilizers or microwave its material? Now it keeps on eating everything, and liver evolved because most of the substances they pass from the git through the liver to the circulation. So liver was a major detoxifier system, and it is still major detoxifier system, right? That liver has a responsibility to convert the lipid soluble substances or toxins or drugs or other substances into more water soluble substances. And then if a better side threw that substance into building system, they will go out through petability system, or hepatocytes through such substances into a circulatory system, they will go out through urinary system. Am I clear? Now we have discussed that Many metabolic waste product go out through urine as well as many many drugs go out through urine, especially there more polar metabolites, is that right? So we can say there are many drugs and third substance which goes out, third type of substances like toxins, many toxins which also enter in your body, right? Not all of the toxins, but many toxins will go out through urinary system. Do you have any question here? No.

Now very briefly, what are the special regulatory functions of the kidney? What are the special regulatory functions of the kidney? Up to now we have discussed the excretory functions of the kidney. Now we are going to talk about regulatory functions of the kidney. They regulate balance of certain substances in our body. First of all, kidney is very well known to regulate the water balance. All of you know that if you take more water, it will pass out more water. If you take less water, kidney wheel comes out of the water, we'll we'll discuss in detail later how kidney makes tell you to urine and concentrated urine, but it is very important for water balance. Then it is also concerned with electrolyte balance. It is also concerned with Electro light balance, electrolyte balance, serum electrolyte balance really depends on renal function, good renal function, right? And third regulatory function is, yes please, that is also extremely important. Kidney plays a major role along with the lung, and that function it regulates something in your body so that your enzymes work well, because enzyme work on a specific pH. So kidney is regulating acid base balance. Again there will be three hours lecture on this, three or four hours lecture that how kidney is regulating the acid-based balance in your body and how kidney diseases produce acidosis and alkalosis, but we are just laying down the foundations today. Fine. So kidney is concerned with water balance, it is concerned with electrolyte balance, it is concerned with acid-base balance, is that right? Okay, about the electrolyte, I don't know, I'm a bit sensitive or why, because good students should know at least the balance concentration of few important electrolytes. What is the sodium concentration in a normal person in the blood? Sodium level in the normal person, yeah, of course in the blood, yeah 140. Watt 140 kilograms milligrams machine guns? Yeah, 140. You should always remember units, we are doctors. Yes, 140 Watt millimole per liter, right? Anyways, good, still he should get the credit, he remembers 140. Sodium is 140 Milli mole per liter. We can also call it 140 Milli equivalent per liter, but you know our body has not read the books, so it's little bit fluctuate, isn't it? So truly speaking, normal sodium level should be considered 135 to 145 Milli equivalents or millimole per liter, same thing, five unit up or down is well tolerated, is that right? When you are in the junior classes, you should remember central figure, but as you become more senior, you should know the normal range, because you are going to be a doctor and you must know when to consider your patient normal and when should we considered the electrolyte imbalance has occurred, right? So it is about 135 to 145 Milli equivalents or millimoles per liter. What about potassium level? Normal potassium level in the plasma or blood? Yes, Mr vocas is trying to say something. 60 to 80, you will find this level normally in the graveyards, right? I want a living human being. What is the level of potassium in living human beings who are normally functional, is that right? Normally functional, yeah, how much? I don't know, he has said low or high, five words, thanks. Yes, you always mention the journals with it, right? That's good. Potassium is again, good boys should remember the whole including the good girls uh range 3.5 to 5.5 millimolo Milli equivalence per liter, is that right? That is too dangerous, you know about when people reach at the level of 7.5 or 8, usually they are dead. That's not right. So I don't know, maybe you have been putting the potassium into dead body, right? So anyway, no problem, you are going to work such formulas, you know it is being recorded, they will catch you right with your intentions. Okay, now what we are talking about that I'm just kidding, right? So 3.5 to 5.5 Milli equivalent per liter is the normal range of potassium level, and every good doctor should know well. But you know your central CPU become really tired, and if you want to remember one of these value which is more important, Dr nazanin will tell us if you have to remember one of these value, for example you are those type of doctors, I cannot remember to already have to remember many other things in my life and you are left with to remember with one which you will choose in clinical practice for patients life and death matter, both are important, but which is more important? Yes, potassium level or sodium level? Sodium level? Yes, potassium level? Yes, sodium level? Yeah, potassium this time majority is Right, potassium level is extremely important again because was eventually right somehow. So actually potassium level is more important, you know why? It is already little fluctuation potassium beyond the normal value kills the patient sometimes, right? We say if patient has a potassium level, you cannot study renal system without knowing electrolyte. Why I'm telling you these things because later on I will tell you how nephron is dealing with electrolyte and why it is so important. Look, if this level is less than 2.5, right, we say the hypocalemia, and if it is more than 6.5, we say there is a hyperkalemia, and hypokalemia sphere hypokalemia as well as severe hyperkalemia both hand precipitate dangerous cardiac tachythmia and kill the patient. How they produce tracheurysmia will talk at later, right? So if you remember only one, please remember potassium level rather write it down that out of whole electrolytes in the body the most important to remember the level is potassium. After that you can come to others like sodium or calcium. Sodium level 135 to 145 Milli equivalent per liter, but it can be tolerated even if it falls to 125 or it rises up to 155, is that right? But little fluctuations in potassium are going to kill the patient, so you have to be very very sensitive when you look at a report of the laboratory, right? Lab report from the patient that what is the potassium level, and again who is the master regulator of potassium level? This is your goodness, you know potassium is control at Exit level, it is regulated in your body at exact level, it exists through it enters through oral cavity, you know you take a lot of food which are very very rich in potassium, and it goes production goes out through mainly goes out through urine, is that right? Do you think you are all the time wearing potassium into food? Never bothered, no one bothered, isn't it? Why because kidneys so Master regulator of potassium handling that if you take more potassium it will pass out more potassium, if you take less potassium it will pass out less potassium until kidneys are absolutely healthy and their function is not altered by the drugs. In future I will tell you many drugs change the function of the kidney, is that right? Again listen, there are some substances their control at the entry level, for example the classical example is iron. You know in many food there is iron, only you absorb the iron which is required, extra iron is lost into fecal matter, so it means iron absorption is regulated at entry point. What is the entry point? GID mucosa, is that right? Usually in a healthy person we don't absorb extra iron, even if we put on the diet extra iron, it will be lost in fecal matter, but potassium is not well regulated at entry point G80 mucosa, usually whatever potassium is coming most of it is absorbed, where it is well regulated at Exit point, that is it exists through kidney, so nephrons later on I will discuss us so Master regulator of handling the potassium whenever the sense potassium is going up the start secreting potassium in higher amount into urine, and whenever this sense potassium is lower the body they reduce the waste of potassium. We'll talk about that later in detail. So anyway, here we also know there is something called chloride, isn't it? If you know the levels of two Cate ions at least you should know the level of one anion. What is the normal level of chloride? It's around 100, it is around 100 Milli equivalents per liter, up to 105 is okay, is that right? So you can say around 100 Milli equivalents per liter, but of course little up and little down is normal range. And what about the bicarbonate level of bicarbonate is also electrolyte, isn't it? Am I right? By car it is The Alkali of your body, the base of your body playing a major role in acid base handling and pH of the body. Yeah, what is the normal level of bicarbonate ions? No one knows, I'm dealing with the doctors, future doctors. Okay, yes, any estimate but not like graveyard estimate, any guess? That's the graveyard. Totally speaking, to go back there 135 is a very high level of potassium in a dead body, you have to inject potassium uh it effort is possible but it is alkalosis during the day it's less than that before you tell me something new, it is somewhere between 22 and 28 Milli equivalents per literal per liter or 25. On average, is that right? Okay, this was some talk about the electrolyte balance. So this is a kidney which has to control the sodium balance, it has to control the production balance, it has to control the on the right balance, it has to manage the bicarb balance, and of course you should not forget your front which keep you strong, that is calcium, is that right? Calcium balance is also controlled by kidney and many other organs that we'll discuss sometimes else, but what is the normal level of calcium in the blood? Because very soon we'll leave the renal physiology go to the renal pathology, then we'll talk about these electrolytes that Disturbed, so it's good at this point we must know what is the normal level of calcium. About 2.5 millimole per liter, about 2.5 approximately milli mole per letter, right? So we have discussed about few excretory functions of the kidney and some regulatory function of the kidney. If you are not tired, we can continue with the endocrine function of the kidney. Should we continue? Okay, so so kidneys and endocrine gland as well. How do you define an endocrine gland? Just how do you define endocrine gland? Is any collection of cells which produce a substance and release into blood and that that substance is carried away from there and act to another group of cells, one group of cell producing a product which is passing through the blood and altering the biological action of another group of cells, there's this is the definition of endo endocrine glands and hormones. Am I clear? So kidney is an endocrine gland as well, right? Right kidneys endocrine or left both. Okay, that's good, he knows it. So what are the hormones which are produced by the kidney? Yes, what are the hormones which are produced by the kidney? Erythropoietin, excellent. First of all, erythro ating, excellent. Second is renin, this is also produced by the kidney. Then another hormone which is produced by the kidney, ADH acting on the kidney. I think up to few minutes before ADH was produced by the hypothalamus and stored in the posterior pituitary, it is still doing the same thing. Okay, it acts on the kidney. Hormones from the kidney are different and hormones acting on the kidney are different. So I'm talking about hormones from the kidney, produced by the kidney and acting somewhere else in the body. So we have discussed that there are erythropoietin and there is ran in and any other hormones which are produced by the kidney? Have you heard of prostaglandins? Many kidney cells produce prostaglandins which regulate the intra-renal blood flow, blood flows within the kidney and even outside, right? So but mainly in the interaction also prosta glandins production, is that right? It produces prostaglandins, that produces ran in, prostaglandins are mostly vasodilators, renin work with you know it that will convert angiot and Cyanogen into Angiotensin one which is converted into Angiotensin to an angiotensin two really forces the release of aldosterone plus Angiotensin II produces Vino construction, artery Construction Plus endurance into stimulates sympathetic nervous system. Angiotensin II produces thirst and many other functions, right? So they are so angiotensin two levels go up when in the blood renin level goes up. Again we'll talk in detail later. Erythropoietin, okay, that's interesting situation. Which cells in the kidney produce erythropoietin? I think it's a difficult question or something. Oh my God, he's telling I asked which cells in the kidney, which cells in the kidney produce erythropoietin? You say white blood cell in the kidney producers providing, right? You should get a big price for giving an answer which no one knows in the world. Yes, it is wrong of course, right? I thought maybe some one of the video recorded as the right answer. So in the kidney which group of, okay, this is difficult question, you tell me in the kidney bit cell produce renin. Foreign, okay, that's good. So renin is coming from there, erythropoietin from where it is coming? If any one of you can tell the right answer he can get at least 10 dollars for me which I don't have right now anyway. Foreign. Yes, I think you become active if you are interested in ten dollars. My question is which cells in the kidney produce erythropoietin? Yeah, of course, if we say kidneys producing Electro protein, there must be some cells in the kidney where genes are activated making the messenger RNA, the messenger RNA is translated, then a protein is produced and that protein is called erythropoietin. Did you get it? So which cell in the kidney? Yes, yes, if this is kidney and here is your Nephron, you know in the nephron there's proximal convoluted tubule, then there's Loop of Henley thin part thick part, I will teach you detail later, then this is distal convoluted tubule and collecting tubule, from here the urine has go out. These are proximal convolated tubules and here there are distal convolated tubules around them their capillaries which are called peritubular capillary Network capillaries around the tubes Parry perimen round Berry tubular capillary Network, right? For example one capability out of that Network I draw here, this is a n disability is of course having what, what are these cells? I think these are endothelials, right? A special type of epithelial and Achieve yourself, is that right? Now these endothelial cells, if I make one endothelial cell out, right? These endothelial cells they are very very sensitive to oxygen levels, they are having a special type of proteins and these proteins are called oxygen sensors. What are these proteins called? Oxygen sensors within these cells. So when blood is passing through this area, oxygen goes into these cells and they activate the oxygen activate the oxygen sensing proteins. Oxygen sensing proteins go and block certain genes. This oxygen sensing protein will go into the go into nucleus transport into nucleus, when they are having the oxygen they go into nucleus and inhibit the genes for erythropoietin production, they inhibit the genes for erythropoietin production. This blue Gene is erythropoietin producing Gene, am I clear? Now what really happens when and your blood rbcs are less, if they are reduced rbcs there is anemia, isn't it? Then there is reduced oxygen supply, and if there is reduced oxygen supply when there's anemia, RBC mass is less, total RPC mass in the body is less. Do you think you are carrying more oxygen in the blood or less if there's less oxygen reaching there? Then oxygen sensors are not getting the oxygen, and if they are not getting the oxygen they cannot inhibit the erythropodin producing genes. So erythropoietin producing genes are released from the inhibitory action of oxygen sensors and they they produce what, they produce messenger RNA which will of course you know go to ribosomes and then that well they will make a new protein and this protein will fold and come out as erythropoietin. Are they throw point in this urethropoietin through the blood will go to the bone marrow house? What is this bone marrow house? The Sarasota protein will go into bone marrow house and there it will act on the cells which are responsible to produce rbcs, which are responsible to produce rbcs. So erythropoietin will go in the bone marrow, it work on a precursors of a retired series, the cells which will lead to formation of RBC is there in the presence of erythropoietin those cells start working more, they survive more, they live longer, they proliferate more and they make more obvious. You may be thinking words are fun to explain it at this moment, the reason being there's a lot of clinical talk about it these days that if your kidneys fail, both kidneys fail, there are many problems in the body and both kidneys fail, there are many problems in the body including this, there is reduced erythropoietin production. So patients who have chronic renal failure, both kidneys not functional and destroyed by some disease norethropoietin reduced RBC production and patient develop swear anemia. And these days how we are managing that anemia? Now we have you can say genetically engineered the formation of erythropoietin. We have taken the gene of rethropoietin planted into geisten bacteria and those yeast and bacteria provide us genetically engineered arthropoietin and some these days if someone has chronic renal failure both kidneys are destroyed we give him injections of erythropoietin so that this should go to the bone marrow and increase the reciprocity activity. Am I clear? Sure. So now you have to remember yeah, how long does it take? Oh, this is very important that if I give you injection of erythroprotein right now, it will take about one week.

That is it. It will start raising the RBC level, right? It was a good question. Now, erythroportion—you know exactly from where it comes, right? It is from endothelial cells present in the peritubular capillary network. Renin comes from juxta glomerular operators. In some lectures previously, I told you that here is the afferent arteriole, here is glomerulus, here is efferent arteriole. This is our afferent article. Some cells in the afferent arteriole, they are modified here, and these cells are called—they have—these are the part of juxta glomerular operators because this—this operator is made by modified vascular cells and modified renal nephron cells. This group of renal nephron cells are called macula densa, and this modified epithelial cells are called pulcation; anyway, but both together, right, both together modified vascular cells make this pulcation and modified nephron cells and distal convoluted tubule put together; they make a structure which is called juxta glomerular operators because the apparatus is just along with the glomerulus, and whenever this is stimulated, it releases renin from here. So, the source of renin is juxta glomerular operators, right? Prostaglandin is produced by many cells. Okay. Is there any more function, endocrine function of the kidney? Okay. Can we go to the metabolic functions of the kidney? We go to the metabolic functions of the kidney. Yes. Who is going to tell me some metabolic functions? No, that is the regulatory function. If it is—if kidney is dealing with the acid-base balance, that regulates the acid-base balance. We have discussed it already. What is the metabolic function of the kidney? Number one. Number one: it activates the precursor Vitamin D. It converts the inactive vitamin D into active vitamin D. Is that right? I will not go into detail at this level, but still, normally you know Vitamin D—let's suppose that's when sunlight falls on the skin, right—in the skin 7-dehydrocholesterol produces a product which is called cholecalciferol. What is it called? Cholecalciferol. You have heard of it. This substance will go to the liver, and when the substance comes out of the liver at its 25th position, it has one added hydroxyl, so we call it 25-hydroxycholecalciferol, but it is still inactive. So, when cholecalciferol passes through the hepatocyte, it gets hydroxylated, and its first hydroxylation is at the 25th position, but it is still inactive. Then it passes through the kidney, you know, and the kidney—it passes through which cells? There's some group of cells, of course you will answer, not me, right? When it passes through those cells, they add one more hydroxylation. First hydroxylation, the hepatic hydroxylation is at the 25th carbon of the molecule. Then it passes through that; it converts into 1,25-dihydroxycholecalciferol. This is the really active form of vitamin D. This is the active form of vitamin D. Is that right? This is the active form of vitamin D, right? So, the kidney has a metabolic function to convert the inactive vitamin D into active form. The question is that which cells of the kidney do this function, right? You know every doctor may be knowing this—their kidney is doing it, but if you are really too good, you must know which cells in the kidney are converting inactive vitamin D into active vitamin D by hydroxylation by hydroxylation at carbon number one because those cells have an enzyme which is called Alpha-1-hydroxylase enzyme. What is the name of that enzyme? Alpha-1-hydroxylase enzyme. You may have heard of it somewhere in your past. Alpha-1-hydroxylase enzyme. Though that enzyme is present in which cells of the kidney? Yes, please. Anyone feel free to answer. Don't hide your knowledge. You can answer as far as you are wrong. Yes, no. Paul, the question is supposed to produce renin. Yes, any guesswork? Nothing. Amal, you are left. Sharon, that which cells in the kidney can convert inactive vitamin D into active vitamin D? Have you heard of something called proximal convoluted tubules? Those cells—look at this cell, you know—after just—this is the proximal convoluted tubular cells. These cells are having—these cells are having Alpha-1-hydroxylase enzyme. So, what are these cells? These are the cells in proximal convoluted tubule, and vitamin D enters into that and then comes out as double hydroxylated. Is that right? So, these cells—proximal convoluted tubular cells—these cells are very rich in Alpha-1-hydroxylase enzyme, which is supposed to convert inactive vitamin D into active vitamin D. How? By converting 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol. Is that right? Did you want to know who stimulates this enzyme? There is something which stimulates this enzyme and tells this enzyme, please activate the vitamin D; we need calcium in the body. Parathyroid hormone, you know, parathyroid hormone acts on these cells and gives a stimulatory signal for the Alpha-1-hydroxylase so that more and more inactive vitamin D can be converted into active vitamin D. But that will study in detail when we talk about endocrinology. Is it okay? Alpha-1-hydroxylase enzyme is present in the renal cells. Which renal cells? Proximal convoluted tubular cells, right? This enzyme is present over there. Am I clear now? What is the—this enzyme is supposed to convert inactive vitamin D to active vitamin D, but of course this enzyme should have some order; something should stimulate it so that it started function. So, who stimulates this enzyme to convert more vitamin D into active form? The answer is parathyroid hormone because parathyroid hormone comes from the parathyroid gland. The parathyroid gland has Chief cells. You know what a parathyroid gland is. Chief cell—on the surface of the Chief cell, the calcium sensors—on the surface of the Chief cell, the proteins which are called calcium sensors. So, when calcium binds there with the Chief cell, it inhibits the parathyroid hormone release, but if in the blood calcium level becomes less—ionized calcium becomes less—then there is—calcium sensors sense no calcium in the blood or less calcium in the blood; they immediately force the cell to release parathyroid hormone. Parathyroid hormone does a lot of function. One of the functions is it will rush towards the proximal convoluted tubule and stimulate Alpha-1-hydroxylase enzyme so that more and more inactive vitamin D is converted into active vitamin D, and when you have more active vitamin D, active vitamin D will rise to—active vitamin D will rise to the GIT mucosa, excellent, and in the GIT mucosa it will help absorption of calcium. Now you see who sends the low level of calcium? Chief cells, but they release calcium manager. Who is the calcium manager? Parathyroid hormone. It does many tricks to bring the calcium level high. One of—one of the tricks is it will activate Alpha-1-hydroxylase. Alpha-1-hydroxylase will convert inactive vitamin D into more active vitamin D. This active vitamin D will—will go to the GIT mucosal cell, and on those GIT mucosal cells it will activate the genes; it will activate the genetic machinery of GIT mucosal vitamin D so that GIT mucosal cells make those proteins which will help in absorption of calcium. So, calcium-lowering effect was sensed by—and calcium is getting after multiple signaling mechanisms in the body—from GIT waves are more calcium, but parathyroid hormone does many other functions which we will discuss again in this lecture of renal physiology. We will specially concentrate and learn their relationship—relationship between cardiac output—relationship between cardiac output with the renal blood flow—renal blood flow—and what is the relationship between the renal blood flow and renal plasma flow, right? And what is the relationship between the renal plasma flow and glomerular filtration rate, right? And how glomerular filtration rate is translated into tubular flow—that fluid is flowing through the nephron tube—and in the end how it converts into urine output—urine output. Again, this is a very important physiological concept that a good medical student should know. What is the relationship between the cardiac output and renal blood flow, and what is the relationship between the renal blood flow and the renal plasma flow, and what is the relationship between the renal plasma flow and glomerular filtration, and what is the relationship between the GFR and tubular flow, and eventually how the tubular flow—flow in the end—translates into urine output? It means cardiac output is started with the cardiac output; it will end up into urine output. But before we really go into detail of this system, I would like to clear some concepts related with the renal vasculature because urine formation—urine formation is a very important interplay between the renal blood flow and the nephron function. Let me repeat it: urine formation by the kidney is—right—determined by the very close interplay between the renal blood flow system and renal nephron system. So, first of all, I will explain the basic concepts related with the renal vasculature. Then I will explain a little bit about the nephrons, and then I will develop the relationship between the renal blood flow and the nephrons. After that, I will explain these things, right? So, let's go to the very, very basic anatomy and physiology which is required to understand these things, right? Let's suppose that here I make a kidney. All of you know that this deeper part of the kidney—this is medulla, right? I have made it three medullary areas; of course there are more, right? But inner and outer part is—yes, please. What is it? This is cortex. This is renal cortex. This deeper part is renal medulla, and here we can say okay, I'll make the calyces more clearly. These are the calyces system, right? And here is the renal medullary system. Is that clear now? Already you know that this is renal cortex, this is renal medulla. There is a urinary collecting system, but we have to develop the relationship between the renal vasculature and the how the nephrons are fitting into this picture. So, let's start with the renal vasculature. Uh, this is aorta. You know from the aorta the renal artery is coming, and the renal artery—of course, abdominal aorta—it will divide into posterior division and anterior division. This will divide into posterior division and anterior division will be of course going to the posterior side of the kidney, and nutrient is coming interiorly. This is the anterior division, and here is the most shared vein, and this is the main renal artery. Here is the main artery dividing into posterior division and anterior division. Then from these divisions, branches will go to every lobe. For example, this is one, and interlobar branches—this is going to another lobe. Here is an artery which is going to another lobe, so and so forth. So, what are these branches coming from here? These are interlobar branches, right? These are interlobar branches, right? Now, let's suppose an interlobar branch reached at the junction of cortex and medulla. They divide into these branches which are arcing over medulla and cortex junction. These arcing branches are called arcuate branches. In the same way, this will also lead to—what is this branch, please? Or create—this is going to arcuate. Here it has gone to arcuate, and this will also go to arcuate arteries. What are these—which branches, please? Arcuate branches. You can repeat it with me, no problem. So, again, listen carefully. This was the main renal artery, right? Number one. Number two, you go for divisions. Number three, you go for inter—what is this? Lobar—L-O-B-R—interlobar branches. No problem to here. Then they divide into this—fourth number—what is this? Yes, arcuate branches, right? Now, what really happens from the arcuate branches—from here there are branches which are straight going into deeper part of—what is this?—cortex, and these branches are called interlobular branches. What are these? Interlobular branches, like this, and they are of course present throughout. What are these branches, please? Interlobular branches, right? So and so forth. So, they are present throughout, but I will not make throughout. Do they have to explain a few more facts? So, this was arcuate artery, and this was arcuate artery, and from here interlobular branches. Now, let's suppose we concentrate on one interlobular branch. This is one interlobular branch. What this branch is doing—you know from it—these are small arteries which are going on the side. What are these arteries? Yes, a bus—you can tell me what are these arteries? They are going on the side; they are offshooting from the interlobular, right? Yeah. What are these called? Afferent arterioles. These small branches are afferent arteries, actually. These afferent arterioles are supposed to bring the blood to glomeruli. Is that right? Now, these afferent arterioles will break down into capillary network, right? They will break down into capillary network, right? And this capillary network which is made over here—what is this called? Glomerulus. What is it called? Glomerulus. What is glomerulus? It is a capillary network which is produced by the breakdown of the afferent arterioles into capillary network. Am I clear now? Here is your—okay, I will just remove this collecting system to reduce the complexity of the picture, but don't forget the kidney is really complex, but very, very interesting to learn. Now, from this nephron—glomerulus—this is now—I'm trying to develop the relationship between the vascular system and nephron system. This is the beginning of the renal nephron, you know—Bowman's space, right? The bunch of capillaries of glomeruli are enveloped whether Bowman's space, and then this part of the nephron—they break down into proximal convoluted tubules, you know it, and then from the proximal convoluted tubules—for example, this is proximal convoluted tubule—of course, it's in the cortex—from here this is going down into medulla, and this is called loop of—yes, please—Henle, and then it develops a thin turn here, and then it develops a thick part of loop of Henle, and the thick part of loop of Henle turning from medulla to the cortex, right? And then this will divide into—what is this?—distal convoluted tubule, and the distal convoluted tubule again turns into medulla as collecting system—collecting tubules—and then medullary collecting tubule, then eventually collecting duct, and from this point what will come out? What is it? Urine. Is that clear now? What we have seen here—that we have seen that this is proximal convoluted tubule—Bowman's capsule—proximal convoluted tubule—loop of Henle—what was this?—distal convoluted tubule, and distal convoluted tubule will eventually break—converted to—collecting tubule—this is collecting tubule—and then eventually this is going to the medulla. Is that right? Now, this glomerulus is in the cortex, but some glomeruli are very, very near to the junction of cortex and medulla. For example, if glomerulus is formed here—suppose it is a glomerulus here—this is more near to—where—to medulla. Such glomeruli are called juxtamedullary glomeruli. Such glomeruli—this one type are called—are cortical glomeruli, and about 10 to 15 percent—there are slight anatomical and functional differences which I will explain, right? First, we concentrate on this juxtamedullary glomerulus. How it works? Now, what you have learned? Yes, what was this artery coming in this place? What was this artery coming? Afferent. This was afferent artery. This artery breaks down to rays which is called capillaries, and within this capillary network there is some connective tissue and cells. What are these connective facial cells? What are these connective facial cells? There's some—these capillaries—look—this is an afferent arteriole. It breaks down into capillary network. This is efferent artery. This is efferent, and here it was—what was it?—afferent. Through the afferent blood was coming, and through the efferent blood is leaving the glomerulus. Suppose here in the diagram I have shown two loops of capillaries—one loop of capillary is this one, another loop of capillary is that one. Am I clear? Actually, normally one efferent arteriole makes 10 to 15 loops or bunches of capillary networks, right? Now, here is—what is this?—Bowman's space. Is that right? Of course, you know this is also made of cells. We'll talk in detail about that later, right? I was asking that this capillary bag—this is embedded into some special type of connective tissue. You see it—this blue connective tissue. I want to know—measures should be very, very clear about this connective tissue through which the capillaries are looping—your understanding exactly what is the position of this connective tissue. Look, if my fingers—if my fingers—let's focus on this—if my fingers are the loop of capillaries, right? This loop of capillary is applied on one side of Bowman's capsule, but in between the capillaries there is some connective tissue, and here is also some connective tissue. What is this connective tissue called? You have heard of it. I'm very sure you are—even for USMLE—Stefan, even you are supposed to know the diseases of mesangium. This is called mesangium. Have you heard of mesangium cells or mesangial cells? Here, in your life, especially when you sit down for some good medical education, these are called mesangial cells and mesangium, is that right? Now, what really happens? Look, it's a very unique type of capillary network. This is a very unique type of capillary network. Normally, in most of the places in the body—so capillaries—on one side of arterioles, other side they have veins, but this is unique that on one side it has arteriole; another side it has also arteriole. So, it means this network of capillaries is present between two arterioles, not between one arteriole and one vein. When you—you know—we knew the very low pressure system, but arterioles are very high pressure. So, uh—because these arterioles remain constricted—so pressure in the glomerular system will be low or high? It will be high—the pressure as compared to other capillaries in the body because—and most of the time—okay, let me tell you a simple example. In most of the places in the body this is the artery, and here are the capillaries, and then this artery will break down into what—when this is a very low pressure system. So, it's a high-pressure blood is coming with high pressure; it falls into the capillaries and drains into a low-pressure system. So, pressure within the most of the capillaries is very low, but if you put an arteriole here as well as you put an arteriole here, then pressure in this area will be very, very high. This is a unique thing about the capillaries of the glomerulus that this capillary network is—you can say—having arteriole in the beginning—efferent arteriole—and even they come—the blood to the capillary network is coming from arteriole, and even draining into arteries. So, it's a very high-pressure capillary system, and this high pressure helps in higher rate of filtration. The fluid will filter from this capillary area to where—to the urinary space. Fluid will filter into urinary space. We'll talk about that later in detail, of course, right? Now, this is afferent arteriole. Let me make it here that this is—now what is it?—efferent arteriole. Now, where the blood from efferent arteriole will go? Now we have to see—keep it focused—where the blood from efferent arteriole will go. Any one from you—no idea? Look, it goes along—that is very true, but we are right. Look, it will again break down into capillaries. It will again break down into—and now this capillary race will be draining into true veins which will take the blood back. Are you understanding now? So, it means look here that afferent arteriole leads to one—first group of capillaries—breaks and takes the blood into efferent arteriole which breaks down into second group of capillaries. Then blood from the second group of capillaries really drains into the venous system of the kidney. It means the first capillary network is a high-pressure system, and the second capillary network will be a low-pressure system. So, let me make it here on this diagram. This is—what is this?—this is proximal convoluted tubule, and this is loop of Henle. This—efferent arteriole will break down into capillaries and these capillaries, right? Actually, if you truly see them, capillaries move around this proximal convoluted tubule. Now, what is the purpose of these capillaries? Let me tell you, these capillaries—this capillary network—called peritubular capillary network. There were two capillary networks—one here—this is glomerular capillary network, and this is peritubular capillary network. Peritubular capillary network—peritubular capillary network is enveloping—it is surrounding the proximal convoluted tubule as well as distal convoluted tubule in the renal cortex. Let me show you here—truly speaking, this network of capillaries—it is like this, right? You are understanding. I have just made it an easy diagram, but actually they just break it into capillaries which go around the proximal convoluted tubule as well as distal convoluted tubules. Am I clear now? And then what is the major function? You know proximal and distal convoluted tubules are playing the major role, especially proximal into a lot of reabsorption and secretion. So, a lot of substances which are filtered are reabsorbed from this area back to the blood. A lot of substances which are filtered, like all the glucose which is filtered within physiological limits, that is reabsorbed to carry—tubular capillary network—or all the amino acids which are filtered, they are reabsorbed, and many more substances we will discuss later. Am I clear, right? And then, of course, these veins will go back into interlobular veins and arcuate veins and interlobar vein—then between the vein—and then into renal vein, and of course not into your time too—not into aorta—into inferior vena cava. Is that clear? There's no need to remember that thing, but basic stuff—the vascular system is clear to you. Fine. So,

We can say that cortical structures listen carefully. Cortical structures of the nephron are provided by two capability networks. Number one is peritubular. Triple A network. Is that clear? Now a little complex thing is coming. I will explain it to you. Let's suppose, what is this? This is your—yes, what was this? Please tell me. These are—these were—these are the afferent arterioles. What are these? Afferent arterioles. These are capillary capillaries, and these are different. Is that right? Now, and now this nephron is in the cortex. This nephron is also in the cortex. This is also in the cortex. This nephron is very near to the medulla. These three glomeruli will be called cortical, but this glomerulus which is very near to the medullary line is called juxtamedullary, right? Which is very, very near to the what? Right? It has a different relationship. It has a very short proximal tubule, very long—what was this? Loop of Henle, and then it has a very short distal convoluted tubule and collecting system. Is that right? A mic layer, am I right? That this was cortical glomeruli. What is this? Juxtamedullary. Now the real difference is in their afferent arteriole. You know that these afferent arteries will break down into what type of—is very tubular. What they break down into? Very tubular capillary networks. But this will not break on to peritubular. This will make loops which will not go around that. These capillary loops will go down into where? Where they are going into medulla. Are you understanding? Nothing. That different arterioles from cortical glomeruli, they break down to peritubular capillaries, but different arterioles from the juxtamedullary glomeruli, they break down into loops of capillaries as we go deep down into medulla. And then from medulla they return back into cortex. This long loop of—is—is called vasa recta, because these are straight vessels. They call them—have you heard of vasa recta? Good. So these are called vasa recta. Actually, vasa recta, later on, I will tell you they're playing a specialized function in maintaining blood flow. Very little blood flow in the renal medulla. They are maintaining a very little blood from the renal—in a renal medulla, right? So now, and of course when this vasa recta turned back, they also drain into veins, and these veins will take the blood back. I will not go into detail of this venous pathway. You can understand. And vasa recta will come back; they will go into veins, our great veins, then into inferior veins, and then into renal veins, and you know it eventually ends in inferior vena cava. Is that right? The point which I wanted to highlight, I will again highlight there because it's worth repeating. Right now, you people will tell me how it goes. I'll draw another kidney, and now this is your test that have you understood this concept or not. I think someone has kept over here. Okay, listen. Here is medulla. I will make it like this. This inner area is cortex, and here what is this? Is that right? Now listen carefully. These are the—I will make only one example. This was arcuate artery, isn't it? Interlobar artery or arcuate artery, and what is this? Interlobular. And from the interlobular, what is it? Afferent. And this afferent is going into which—uh—glomerulus or juxtamedullary? Cortical. And I make another here so that you really understand. Okay, what is this? This will make our—what is this? What is this glomerulus? This is cortical glomerulus, Bowman's capsule. What is this? Proximal convoluted tubule. Is that right? Right. And from this proximal convoluted tubule, proximal convoluted tubule, these are loop of Henle, and it is turning its back then into which? Distal convoluted tubule, and in the end, collecting system. Is it clear? Now this will break down into what kind of capillary? What are these capillaries? Peritubular, is that right? And then returning back to the venous system. Is it clear? No problem after this. Yes, please. This is afferent arteriole. This is different. This is interlobular. This is arcuate, you know, interlobar, arcuate, interlobular, afferent, peritubular capillary, tubular capillary network, venous drainage. Hello, I think okay. Now the difference is—what was this one? It was which one? The summary now. Juxtamedullary. It has a Bowman's capsule, and it has also—what is this? Is it clear? Look, and its vascular system and its remaining nephron. It is juxtamedullary. Now the beauty which you have to appreciate is that this afferent in the cortical was breaking down to which capillary? Peritubular. And this will break down into which capillary? Vasa recta. So they will straight go down like this, and they will call back, and they will also go for the—now from here venous return. Is that right? So this is vasa recta. About 90 percent of blood flow is through the cortical system, and about 10 to 15 blood flow is through what is this? Juxtamedullary. 90 to 85 to 90 percent of glomeruli are cortical. About 10 to 15 percent glomeruli are juxtamedullary. About very most of the blood flow is through the cortical system, and through the vasa recta there's very little blood flow. Teach you that in the medulla there is hyperosmolality. There are a lot of solutes concentrated into medulla. I will explain later. There's a lot of solutes—welcome. With lot of solutes are concentrated into medulla. It's very high concentration of solutes, right? Now we say there is medullary interstitial—medullary interstitial hyperosmolality. Later on, I will tell you what is the purpose of this, but this hyperosmolality is created with use of a lot of energy, and it helps in concentration of urine. Right now, because we have concentrated a lot of solutes into medulla, body does not want that these solutions should be washed away. Should they be washed away? No. Now if we don't want them to be washed away, then blood flow should be slow or fast? Slow. If you have some mud here, water flow is very fast; it will wash away. Water is going little back; it will not wash away. So in the same way, vasa recta has very little blood flow so that medullary interstitial hyperosmolar setup should not be washed away. That's right. That I will teach later how this hyperosmolality is formed and what is the purpose of having this area hyperosmolar. Is that right? Any question up to this? There's no question. Okay. Let's suppose that here is your circulatory system. Let's see here circulatory tree system, right? And here is your beautiful heart pumping the blood all your life, right? Now what is the normal cardiac output? What is a normal cardiac—how much blood is pumped by the left ventricle into arterial tree, systemic arterial tree, permanent? What is the amount of blood pumped by the left ventricle into aorta and eventually into systemic arterial tree? That is, you know, cardiac output is equal to what? Is equal to heart rate into stroke volume. That—what is the volume pumped by the left ventricle per stroke, and how many strokes per minute? So you know that is 72 into 70. Heart rate is on average 72 beats per minute, and 70 ml is the blood which is ejected by the ventricle, healthy ventricle, and resting conditions. So become about 5000 ml, right? But per minute. So it is about 5 liters blood per minute, resting, healthy person, approximately. So now you are studying the lecture. I hope you are somewhat resting, uh, at least physically. So what is happening? That 5 liters of the blood is formed by your heart into your circulatory system every minute. Now out of this 5 liters, right? This is the 5 liter blood. Is that right? This is 5 liter blood. And this 5 liter blood, out of this, how much blood goes to the renal system? About 20 to 25 percent. Suppose 20 percent to the renal system. Let's suppose 20 percent blood is going into renal arterial tree, right? Renal arterial tree. There's 20 percent blood going—20 percent blood makes how—how much out of 5 liters? If I say 20 percent blood has gone to the renal blood flow, how much it make? One liter, is that right? It makes one liter. That means that out of 5 liters every minute your both kidneys are receiving one liter of the blood, and of course there is no fun in explaining that one liter blood is equivalent to how many mls? 1000 mls per minute. Out of this blood which is going to the kidney, 1000 ml, this blood can be divided easily into yes cells and what is the other thing? Plasma. Is that right? You know about 40 percent of the blood is cells, so white blood cells, red blood cells, and platelets. They make about how much? 400 ml. The cells are about 400 ml out of the one liter which is passing through the glomeruli. Right? So naturally what is this now? 400 ml cells are passing through the glomeruli. You know how many glomeruli are there? And both kidneys together they're about 2.5 million. I'm just showing one, but the values represent all the glomeruli put together, right? And how much is the plasma now? How much plasma is there? Yes, if 400 ml has gone cells, plasma is 600 ml. So it means through glomerular structures every minute there is 600 ml of the plasma flowing through because cells will flow simply; they do not filter RBCs, WBCs, or platelets. They simply pass through the glomeruli next to the afferent arteriole, right? Cells remain same 400 ml cells, but in the plasma, the 600 ml of the plasma as it is passing through glomeruli, a part of this is filtered into where structure? This is your Bowman's capsule, and this is which tubule? Proximal convoluted tubule, and you know that this proximal convoluted tubule will go into loop of Henle, and this loop of Henle will turn up ascending limb. This was descending loop of loop of Henle, here pin turn, ascending loop of loop of Henle, thin part and thick part of ascending limb of loop of Henle, and here it is distal convoluted tubule, and what is it here? Collecting system and drop off urine coming out eventually. So let's develop the connection. I said that heart is pumping how much blood per minute? 5 liters. Out of that 20 percent is going to the kidneys. It means renal blood flow is 20 percent of the cardiac output or 20 to 25 percent of the cardiac output, that is approximately one liter or 1000 ml blood coming to the kidneys. Out of that approximately 400 mls are the cells and plasma is 600 ml. And plasma is 600. Plasma is 600 ml. Out of this 600 ml plasma, you know cells don't filter; they pass forward. But even plasma is passing through this area, right? Fluid of plasma with the dissolved substances is filtered out of the plasma. Proteins don't filter significantly. Proteins don't filter. It is the fluid of the plasma with some dissolved substances that can filter. But how much out of 600? How much filtered total? It is again 20 percent. This is 20 percent. Now you have to remember out of total cardiac output how much is coming to the kidney? 20 percent. And out of total plasma flow how much is filtered? 20 percent. Now out of 600 ml, 10 percent is 60 ml, and 20 percent is 120 ml. So every minute approximately 120 ml fluid is filtered in every—in all the glomerular spaces together. Is that right? Let's suppose for practical purposes we say it is 100 ml. This is 100 ml, just to make it easier calculation. Just place it—both kidneys combined and all nephrons combined, right? The whole glomerular filtrate, total glomerular filtrate in your body every minute is about 120 ml. Of course it is 60 ml per kidney, right? Now we will see that this 120 ml as it is flowing within the lumen, what happens to it and how much appears in the end as urine. Is that right? That this 120 ml when it is passing through the—what is this? Nephron. In the end, how much comes out as urine drop? What do you think? Out of 120 ml, normally how much comes out as urine drop? 1 ml? Okay. What do you think? 1 ml? How about 65 percent of—right? Again, let's suppose for practical purposes we make it 100 ml. If it is 100 ml which is filtered entering into tubule, about 65 percent will be reabsorbed in proximal convoluted tubule. A lot of solutes with 65 percent will be reabsorbed into proximal convoluted tubule, and remaining is moving forward. Out of this, as it is moving forward, how much is reabsorbed here? 10 to 15. Okay, make it about 15. Of course there is a range, but for easier remembering, out of 100 ml, 65 ml is reabsorbed in proximal convoluted tubule, 15 mls reabsorbed through the descending loop of loop of Henle, and then how much is absorbed from the ascending limb of loop of Henle? Answer is that ascending loop of loop of Henle is water tight under all physiological circumstances, so nothing is reabsorbed from here. You can make a diagram like this. Even if they try, water will not be from here, so it has to move forward. Is that right? It will not be reabsorbed from proximal—sorry, thick part of ascending limb of loop of Henle. Then the tubular fluid will reach to the distal convoluted tubule. Now you have to understand it. We had originally 100 ml here, and 65 was absorbed here. What was entering here? 35 ml. Is that right? Out of that 35 ml, how much is reabsorbed here? Yes, 15. So how much it become? 80 ml. And what is left forward? Reabsorption is 65 plus 15. About 80 ml is reabsorbed. How much is moving forward? About 20 ml. Is that right? Out of this 20 ml which is here in this part, about 15 ml is reabsorbed. So how much is reaching now forward? Only 5 ml per minute. So this is a 5 ml of the tubular fluid which is provided for a minute to the last part of the nephron, and this is the function of the last part of the nephron to fine tune this volume, that how much should be reabsorbed and how much should be allowed to go into urine. Is that right? Normally what really happens as this 5 ml fluid is going down under the influence of aldosterone, 1 to 2 ml or 2 ml or 3 ml is reabsorbed, and a little amount is also reabsorbed under the surface of ADH. This last reabsorption is under the influence of aldosterone, aldosterone which reabsorbs salt and water and expels the secrets of potassium, and ADH which—with the help of ADH you reabsorb the water mainly. And usually in a healthy person how much appears in the urine drop? Is just 1 ml. How much is appearing into urine? This is 1 ml, right? So this was your drop off urine, and here was your collecting duct, right? This is 1 ml per—per minute. So normally 1 cc or 1 ml urine is produced by both kidneys together about every minute. Is that right? Now it means out of 100 ml which was filtered, about 99 percent of the fluid is reabsorbed, and only 1 ml is usually going out as urine. From this we can calculate if every minute 1 ml—blood is—1 ml urine is formed, then how much urine is formed per day? It depends on how many minutes are there in one day. In 24 hours how many minutes are there? Narendra has calculated. I think you never had time to go—3600 minutes per day. I think your day was too long. You are missing someone. Let's calculate truly. Lesson one day. Look, one hour has how many minutes? Let's calculate it. We don't need Arshamitas for these calculations. This is a very simple—you know, one hour is 60—yes, don't tell me 60 ml. 60 minutes, right? And usually in one day how many hours? Sure, 24 hours. So in one day how many minutes? This is 60 into 24 is equal to 1440. Pour it in 1440 minutes per day. If you don't believe it, one day you can spend and calculate it, right? Now listen. Every day we have 1440 minutes, and if you're producing every minute how much urine? 1 ml. So how many ml urine do you produce per day on average? Yes, about 1440 ml, approximately one and a half liters. So normal person produces urine output approximately one and a half liters. But normal range of urine output is—the normal range of urine output is the minimum is allowed 500 ml and maximum is allowed 3000. 500 ml you should produce urine. This is the normal urine output per day, right? That normally you should produce urine more than 500 ml and usually less than 3500 ml. It means that 24-hour urine output should be more than half liter and less than three and a half liters. I will tell you why, yeah. Just a minute before you tell me something new, I will tell you why—why during less—this is bad, and why urine more than this is also bad. Is that clear? But look at one thing that by producing 1 ml daily, you produce one and a half liters. If you produce 1 ml every minute, then it means daily you produce one and a half liters. And if you produce 5 ml per minute, you will produce seven and a half liters. Or if you—rather than 5 ml, 5 ml is going down, all of it goes down here, in output will be seven and a half liters. Or only 4.5 ml is reabsorbed; only half ml goes down here, in output will be about 700 ml. So this is the fine tuning in the last part of the nephron, that last part of the nephron is working on about 5 ml of the fluid to adjust what should be the urine output. But normally urine output should be maintained somewhere between half liter to three and a half liters, right? If urine is less than 500 ml, we say there is oliguria, and if there's urine is more than three and a half liters, we say there is polyuria. Less than 500 ml, is that right? Now before we really close this area, we must know that why it is so important that doctors say that if urine output is more than three and a half liters it should be called polyuria, not normal, and we should also have a very clear concept why when urine output is less than 500 ml it is a pathological condition. I will explain all right. First I will explain why our normal healthy person should not produce urine more than three and a half liters under normal circumstances. Of course, if you drink a lot of water, you will produce more urine, right? Now we will talk about that. We have already discussed if your output is less than half liter or less than 500 ml per day, you see patient has oliguria, and if your urine output is more than three and a half liters per day, do we call it? There is polyuria. We have to think that why for oliguria the cutoff point is around 500 ml, and why for polyuria we put a cutoff point around 3500 ml. First we'll deal with 3500 ml. Listen, first of all, you should be thankful to the nature that it has provided to the urinary bladder because that acts as a storage place when urine is coming, and then you can release or evacuate your bladder as you feel comfortable, socially and otherwise. Clear? Now what really happens for 24 hours more than three and a half liters? Then during eight hours of sleep so much urine accumulates into bladder that it becomes very discomforting, and you have to wake up and pass urine. So it produces nocturia, and quality of life is disturbed. So doctor thought that in a normal person if he empties his—empties his bladder before sleeping, then he should have a sound sleep, and whatever urine he produces around eight hours that should be accommodated into normal bladder well. But whenever your urine output becomes more than three and a half liters, urine flow is so fast that during sleep you have to wake up once or twice or even thrice depending upon the degree of polyuria. Due to this reason they say the normal urine output should be less than three and a half liters because more than that will produce nocturia and struggles with the sleep quality, and life quality. Is that right? You got the answer to this why? Now the question is this: why urologists and nephrologists are very concerned that their patient should produce urine output at least—urine flow? Yes. Urologists and nephrologists, they're very, very sensitive to the patients', and actually every good doctor is sensitive to the patients' urine output that it should be at least 500 ml because if urine output becomes less than that that may become problematic for the patient. Let me explain to you. You know normally—listen carefully—normally uh, what is the concentrating ability of the human kidney to concentrate the solute? For example, when metabolic waste—metabolic waste product which are daily produced, metabolic waste products, urea, creatinine, their potassium and many other substances, these metabolic wastes which are daily produced, right? Normally what happens that kidney has to concentrate them. All the metabolic wastes which are present in our body, they should go out through kidney, and of course kidney has to concentrate and dissolve these metabolic wastes into fluid. Metabolic wastes are not coming out as tablet form or as—

Powder form; they are coming as dissolved form into urine. Is that right? Now, so kidney has the capacity to concentrate these metabolic wastes into the volume of the water. Normally, the maximum capacity of a healthy kidney is around—that healthy kidney can concentrate 1200 milli—or small a mini mold of metabolic waste in one liter of 1000 mL of water. Is that clear?

If kidney death is—best for example, it is water deprivation. If in body has water deprivation, kidney will try to produce less urine, but maximum then, of course, kidney has to concentrate the metabolic waste into minimum volume. But kidney tries to concentrate the metabolic waste and millios right into water. The normal highest capacity for concentration of the kidney is around 1200 or 1400 millimoles of metabolic waste and one liter of urine. Is that right now?

Listen carefully. In a normal person, how many—how much metabolic waste are produced per day? In a normal person with a 70 kg weight, on normal physical activity and on average diet—normal diet, right—such person normally produces daily about 600 millimoles of metabolic metabolic waste. In a normal person, metabolic wastes are per day—daily. So daily, how much you are producing metabolic waste? Around 600 units—600 urine units. Now, 600 units of metabolic waste you produce daily. Now, kidney can concentrate 1200 units of waste in one liter. So, to get rid of 600 units of metabolic waste, kidney should need how much water? 500 mL. That’s it—500 mL of water. So it means that if your urine output is dropping, still, if kidney tries to concentrate all the metabolic wasted minimum volume, it really needs at least 500—kidney needs at least 500 mL of the water to dissolve the daily waste products. Is that right now?

You imagine if urine output is about two and a half—to 250 mL, right? If or your kidney urine output is only the water available into urine is only 200 mL, can kidney concentrate all the waste into 200 mL? No. So what will happen? Metabolic waste will start accumulating in your body. Metabolic waste will start accumulating in your body, and biochemically in your blood—blood chemistry will be altered. For example, urea and creatinine level will start accumulating into—building up into—land. That is why good nephrologists and urologists are very concerned that a normal health person should produce at least 500 mL of the urine so that his metabolic waste should be properly concentrated and cleared out of the body. If person is producing only 200 or 300 mL of the urine, then some of the metabolic waste will be retained in the body and blood chemistry will be altered due to impaired renal function or reduced renal function. Am I clear? Is it—are you clear now?

Tomorrow, if someone asks you then why we have to produce at least 500 mL of urine, you know the answer. Because in less than that, doctors get upset; they get worried how to improve the urine output. Anything you remember from here, you can infer that those patients who have severe catabolism in their body—breakdown in their body—for example, a patient with severe trauma, patient with severe extensive surgery, patient with the burns, patient under accidental breakdown of the tissues—such patients have lot of proteins breaking down in their body. So do you think if proteins are breaking down into amino acids, then they have been producing more urea? So such patients which are having hyper catabolic state, they are having more solute—more metabolic waste or less metabolic equations—the more metabolecules. Who are the patient who are suffering with hyper catabolism? Burns patient, highly traumatized patient, you can say extensive surgery, extensive trauma, or severe sepsis patient—septicemia. They are undergoing very rapid catabolism. Is that right? So any condition—or forget about even a healthy person who takes lot of, you know, chicken and lots of mutton—so you support stuffing lot of proteins in his body and amino acid—so amino acid breakdown will produce more urea and other products. So all those conditions in weight you produce lot of catabolism in the body of the proteins in these hyper catabolic states. Even a very good doctor—only the very good doctor will be upset even when patient is producing 500 mL. He knows that, okay, that normally a person should produce 500 mL, but my patient is under hyper catabolism; he should produce at least 1000 mL, and he will get upset whenever this urine output goes even less than. So it is not something like a return in Bible or some other thing. The important thing is that this thing is you have to think with your mind; it’s not fixed that in a healthy person you need 500 mL at least, but a person—but in a person who is under hyper catabolism and who is producing excessive metabolic waste, you need to run the urine output more than 500 mL per 24. Is that clear to everyone? Right.

Another thing which I would love to tell you that let’s suppose this is your circulatory system, and here are your beautiful kidneys. Only very few people know how kidneys are beautiful, but anyway, I think kidneys are not properly respected and regarded. You know, heart is given unduly more attention. If kidneys are not there, you cannot live. We want to love anyone or to receive the love of anyone, yes, but they are underestimated, you know, like many people.

Now look, for example, if kidney function is impaired, right, and urine output is total urine output is less than 500 mL or 24 hour, that is Olivia. What will happen? That waste product will start—metabolic waste will accumulate. So urea and creatinine level will go up, maybe potassium and many other waste products. Now look, when kidneys start failing, this waste products start accumulating in the blood. When these waste products are initially accumulating into blood, blood chemistry is altered, but still there may not be any signs and symptoms of heart disease. When only blood chemistry is altered and yet there are no signs and symptoms, we call patient is suffering with azotemia. Is a temia. Have you heard of this term, isotemia? What is the isotemia? Isotemia—the clinical pathological condition resulting due to renal dysfunction in which blood chemistry is altered, right, due to impaired renal function—like zuria, creatinine elevated, maybe acid-base balance or electrolyte balances disturbed, but everything is mild, and yet there is no symptoms of signs of a renal failure. But when with the exotemia—when it is a demia plus there are signs and symptoms of renal failure—the condition is called yes, renal insufficiency is already there. What is this condition called? You have heard of it. When someone has azotemia developing pericardial rub, nausea, vomitings, solar skin, other features of renal failure, what is that called? What is this called? It will say yes, now patient has developed uremia. Have you heard of uremia? Uremia is not urine in blood. Uremia is a clinical pathological condition characterized by severe disturbance in renal function which is not only having the acetamia plus also signs and symptoms related with the linear failure, right? For example, patient may develop nausea, vomiting, or with that pericarditis or skin color alterations, acid-base disturbances leading to hyperventilation and many other clinical features, right? Then we see patient is suffering with uremia. Do you have any question up to this? There’s no question.