Greetings. So today we start our organ systems, the urinary system. What we want to talk about in today's specific lecture is the structure of the kidney, which is the dominant organ within this system, the one that generates urine, and then its homeostatic functions. The urinary system has several functions. It balances water and electrolytes within the body. It removes waste products, fluid waste products. So let's see the learning objectives. The first will describe the structure of the kidney itself. Secondly, we'll talk about its homeostatic functions. This is the general overview of the kidney and its role in homeostasis. Third, we'll describe the structure of the kidney nephron. This is the actual filtering unit. This is the small structure that filters the blood. Then lastly, we'll explain the regional functions of the kidney tubule, which is a portion of the nephron. All right, so let's get started. The first thing to note is that the system has two kidneys. Each kidney is connected to a ureter, which is a tubule. So here are two kidneys, and they have tubules, ureters, coming into the bladder. The bladder stores the urine that's generated by the kidneys. From the bladder we will excrete urine to the outside world. The kidney's function is to filter the blood, to remove that excess fluid and excess electrolytes. This maintains fluid balance and electrolyte balance. The electrolytes that we're balancing is not only sodium and potassium and calcium and so forth, but also protons. One of the kidneys major functions is to balance pH. To do so it works in conjunction with the respiratory tract. We'll talk about pH balancing in the next sets of lectures. In addition, the kidney removes liquid waste products. As the tissues undergo metabolism, they generate waste products such as urea. this needs to be removed from the body. This is also a mechanism for excreting drugs, such as morphine or penicillin, and for getting rid of vitamins and other organic structures. And then lastly, the kidney has some very important endocrine functions. The first of these is that makes a hormone called erythropoietin. It does so in response to hypoxia. So low oxygen tension causes the kidney to secrete erythropoietin. Erythropoietin works in the bone marrow to increase the production of red blood cells. The second of these is called renin. Renin is actually an enzyme. It is a hormone that is secreted into the blood, but it acts as an enzyme. Renin will start a cascade which produces two major vascular constrictors circulating within the blood stream. Renin is secreted in response to low blood pressure. The functions of this renin system is to be to raise the blood pressure by raising blood volume. The third hormone is that the kidney activates vitamin D3. Vitamin D3 is made as an inactive form in the skin in response to light. This inactive moiety moves to the kidney where it is activated. Vitamin D3 works in the GI tract to help you to absorb calcium across the epithelium of the GI tract. That calcium is used for calcification of the bone. Okay, so what's our kidney structure? In your body, the kidneys are located at the small of your back. They are retroperitoneal. We usually have two kidneys in a given individual, but there are individuals who have only one. The kidney has, on the outside aspect of the organ, a capsule. It is an encapsulated structure. On one side of the structure there's an indentation. This indentation or concave surface is called the hilus. At the hilus, the renal artery enters into the organ and the renal vein exits the organ. This is the location for the exit of the ureter. THe ureter is sort of a funnel like structure which gathers all of the urine that is generated within the kidney and then transports it to the bladder for storage. The urine then is leaving at this at hilar region. Within the kidney structure itself, the organ can be divided into two zones. There is the renal cortex, which is the outermost area. This is shown here. Then an innermost area towards the center of the organ. This is called the medulla. So we have a cortex and a medulla structure. Now the kidney houses about one million nephrons which are the little filtering units that generate the urine. This is the place where blood will be filtered and then the fluid that's generated will be lost from the body by excretion through the ureter to the bladder, to the urethra and out of the body. These filtering units are located partially within the cortex and partially within the medulla. And we'll talk about this regional distribution later in the lectures. The structure of the nephron is shown here. This stylized drawing shows the two major components to the little nephrons, or to the filtration units. The first is a vascular component. This vascular component consists of a capillary bed, a little tuft of capillaries, which is called the glomerulus. This capillary is fed by an afferent arteriole. The blood that's enters from the renal artery eventually makes it to the afferent arteriole. The afferent arteriole receives the blood. The blood goes into the glomerulus and then it exits from the glomerulus, that capillary bed, by an efferent arteriole. It then enters into a second capillary bed. This is a portal system where we have two capillary beds connected by an arteriole. This is a unique structure. It's the only place in the body where this structure occurs. It is important to the functioning of the actual nephron. The second component of this nephron is a renal tubule. The renal tubule is a blind-ended structure that surrounds the glomerulus. This tubule comes up and it makes a little capsule, or cap, around the glomerulus. This cap, or capsule, is called Bowman's Capsule. That's what's shown here. Then the renal tubule extends from that capsule and eventually the renal tubule drains into another duct, another tubule, which is called the collecting duct. Several nephrons will drain into a single collecting duct. The collecting duct gathers the urine from these separate nephrons, and then that collecting duct will deposit the urine within the deep portion of the medulla at the beginning of the ureter. The urine is then drained from the organ. As we go along the renal tubule, the tubule change in morphology and also it changes in function. There are specific regions. We're going to deal with each of these regions as we talk about the function of the kidney and how it generates urine. The first of these regions we've already described. It is the Bowman's Capsule, which is the starting portion of the tubule, the blind-ended structure that completely surrounds the glomerulus. Distal to that we then have an area which is called the proximal convoluted tubule. The proximal convoluted tubule extends then into a very thin tubule which is called the Loop of Henle and this has a descending portion. Then a central region which makes a hairpin loop and an ascending portion which is called the thick ascending loop of Henle. So the Loop of Henle actually has three components to it. A descending thin Loop of Henle, the loop of Henle's hairpin turn, and then the ascending, or thick ascending Loop of Henle. Distal to this Loop of Henle we have what's called the distal convoluted tubule. This structure drains into the collecting duct. That's shown here. Now there are actually two different types of nephrons present within the human kidney. 90% of the nephrons that are in the human kidney are almost completely located within the cortex. They have very small amounts of the tubules, The loop of Henle barely dips down into the medulla. These nephrons are predominantly located in the cortex. They are called the Cortical Nephrons. They are 90% of the Nephrons in the human kidney. The second type of Nnephron is called the Juxtamedullary Nephron. This Nephron is predominantly located within both regions. It starts in the beginning as a glomerulus and Bowman's capsule. Then the proximal convoluted tubule. These are in the cortex. But the following tubule descends deep into the medulla and then returns back to the cortex to form the distal convoluted tubule. It in turn drains into the collecting duct. This particular nephron is called juxtamedullary, juxta meaning near or next to, the medulla. The juxtamedullary nephron then is the nephron in which the tubule distends deep within the medulla. Only about 10% of the Nephrons of the human kidney are the Juxtamedullary Nephrons. But these nephrons are extremely important for establishing an osmotic gradient within the medulla. This osmotic gradient extends from 300 million osmolar to 1,200 milliosmolar, deep within the medulla. This is within the interstitial tissue of the medulla itself. So we have a standing osmotic gradient. The gradient is made up of sodium and urea. This particular osmotic gradient is absolutely critical for the kidney to be able to generate concentrated urine. Ee'll discuss that in one of the later lectures. Now the kidney receives about 1 liter per minute of cardiac output. So the input then to the kidney of renal blood flow coming through the renal artery is 1 liter per minute. It's actually going to be filtering the fluid phase of that blood. The fluid phase of the blood, as you all know, is called plasma. Plasma is 60% of the total blood volume. The other portion is made up of the red blood cells and other cellular components. So 600 milliliters of plasma per minute, then, are being delivered to the kidney for filtration. Within Bowman's Capsule then, in any given day, we have 180 liters per minute of blood that will be filtered. By the time that you get to the urine, that is, the final output of urine from the kidney, will only about a 0.5 -1.5 liters per day. And that means then that with each pass, we don't filter 100% of the plasma of the blood that's being delivered to that particular kidney. But in fact, we only take a fraction of it. And that fraction is used to generate urine. The majority of that fluid, the majority of the water that's within that filtrate, will be moved back into the body. That way we don't collapse the cardiovascular system. One of the things we’ll talk about in the next few lectures, then, is exactly how the kidney does this. How it’s able to first filter this material, and then move the majority of the fluid back into the body for use by the body. The other thing to notice, is that as we go through this renal tubule, we will change the osmolarity of the filtrate. So the filtrate coming across at the beginning of the tubule that is into Bowman's capsule, will have the same osmolarity as the plasma of the blood, that is, 300 milli-osmolar. By the time we get down to the urine, the final output from the body, the osmolarity of the urine can be variable. It can be as dilute as 50 millismolar but as concentrated as 1200 milliosmolar. We're going to discuss how it exactly this occurs. NOte that the change in the osmolarity of the output, that is, of the urine, is matched to the needs of the body. When the body has excess volume or excess fluid, we put out very dilute urine. But, when the body has insufficient amounts of fluid, or it has more of a dehydration state, then it puts out a very concentrated urine. This process is regulated by hormones within the body, We'll talk about that regulation in one of the later lectures. Okay, so let's look at this. I have drawn now your renal tubule so that we can go through and talk about the different regions, and consider a general overview of how they're working. The renal tubule and its vasculature is diagrammed here. Coming into the glomerulus, we have the afferent arteriole. It comes into the capillary tuff which is the glomerulus. That's our first capillary. Then draining from that glmerulus, we have a second arteriole. That is the efferent arteriole. So the blood then is moving in this direction. It exits the efferent arterial to enter into a second capillary bed. That capillary bed in the cortex is called the peritubular capillary. It is the second capillary. So we have a portal system where we have two capillaries. The glomerulus, which is the first capillary, is in series with a second capillary. They are connected by the efferent arteriole. The second part of the structure is our renal tubule. The blind end of the renal tubule is diagrammed here. It forms a cup-like structure called Bowman's Capsule. From Bowman's Capsule, then, the tubule extends. All along the tubule extends is the peritubular capillary. It parallels the extension of the tubule. The tubule is actually very closely opposed to the capillary. This occurs all the way along the tubule. The first thing that's going to occur is a filtration event. Filtration means that some of the plasma,and only the fluid from a plasma, will cross the epithelial cells that line the capillary bed. It then crosses the basal lamina of the capillary and tubule epithelium, and finally between the epithelial cells which line Bowman's Capsule. That's our filtration barrier. Both size and charge adds to this barrier. Some materials are able to go across this filtration barrier. Cells are not able to go across it, large proteins cannot go across it. But small solutes such as glucose, amino acids, all of the salts, they're able to cross through this barrier, as well as water. Once they enter into Bowman's capsule, then, this fluid is called the filtrate. As the filtrate moves along the renal tubule, it will be modified. One of the modifications is that we reclaim water. We can reclaim salts. we can reclaim glucose, and amino acids from the filtrate and move them back to the blood space. By moving these materials back. They leaving lumen of the tubule, Cross the epithelium of the kidney tubule, and enter into the interstitial space, and then across that, and into the blood. So it's moving across all these barriers, but because the peritubular capillaries closely oppose the tubule. Once materials gets across the cells that are lining the renal tubule, they very quick diffuse into into the blood space. This process is called reabsorption. All of the filtered glucose and amino acids will be reabsorbed in a normal kidney. The majority of the bicarbonate will be reabsorbed in a normal kidney. And much of water will be reabsorbed in a normal kidney, within the first section of the tubule. This is the region called the proximal convoluted tubule. Now the kidney can move materials directly from the blood into the tubule, bypassing the filtration site. This is how a lot of the drugs which are organic compounds, such as morphine, epinephrine, norepinephrine, and things such as vitamins, can move directly from blood space and into the renal tubule. This process is called secretion. Secretion, then, is moving materials in the opposite direction to reabsorption. So secretion is moving material from the blood space back into the tubule. That's shown here. The final product, which is what's excreted from the tubule, is called the urine. Excretion, then, will be the amount that's filtered, minus the amount that's reabsorbed, plus the amount that is secreted. A couple of terms to understand. If the filtration rate of a substance is equal to it's excretion rate, then we have no net reabsorption. Because we can't actually measure reabsorption and secretion for any given, substance, what we talk about, then, is the net handling of the renal tubule. So if the filtration rate is equal to the excretion rate for a given substance, then there’s no net reabsorption, and there is no net secretion. If the filtration rate exceeds the excretion rate for a substance, then we have a net reabsorption. If the filtration rate is less than the excretion rate, then we have net secretion. All right, so the important terms for you to to remember is first, filtration is the movement of the solute in the water from the blood into the lumen of the renal tubule. This is how we generate our filtrate. Secondly, reabsorption is the movement of the solute and the water from the lumen of the renal tubule across the epithelium and across the interstitium, back into the blood. Third, secretion is the movement of solutes from the blood, directly into the renal filtrate, bypassing the filtration point. And fourth, excretion, then, is the removal of the solutes and the water from the body as urine. Okay, so what are our general concepts then? First the kidneys primary functions are to maintain the fluid volumes of the body by regulating the salt balance to maintain the osmolarity of the body by regulating the water balance. To regulate the ionic balance of the body, it's electrolytes, the kidney regulates the amount of water that's in the body, This process regulates not only the osmolarity, but also the size of the fluid space. Secondly, we want to remove waste products, that is products that are generated by metabolism and to detoxify drugs. That's done, again, by the renal tubule. Thirdly, the kidney secrete hormones, including erythropoietin. This hormone is secreted in response to hypoxia. This hormone is absolutely required to generate red blood cells from the bone marrow. Also we have renin, which is secreted in response to low blood pressure sensed by the kidney. In addition, the kidney can activate vitamin D3, which is critical for calcium homeostasis within the body. Fourth, the kidney contains a million filtration units which are called nephrons. Each nephron contains a portal system. An afferent arteriole enters the glomerulus, which is our first capillary bed. This is drained by an efferent arteriole, which then drains into a second capillary bed. We'll talk about this portal system, in detail, in some of the later lectures. And five, filtration occurs across that first capillary bed, the glomerulus. Reabsorption and secretion occur along the renal tubule. And so soluble materials moves from the renal tubule, either to the blood, or from the blood to the renal tubule. This will alter the composition of the filtrate. The final product which leaves the kidney is the urine. All right, so see you next time. And we'll talk some more in more detail about some of the functions of the kidney itself. See you then.