Comprehensive Overview of the Renal System_BILL_DJ_KIDNEY_LECTURE

Hello, welcome to this review of the renal system. Our agenda today is as follows. We'll talk fairly broadly about the functions of the renal system, and as to kidneys, as well as we'll begin with a general overview of the gross anatomy of the kidneys. We'll focus primarily on the structure of the nephron, which is the major functional unit. unit of the kidney. And this includes the following constituent parts, the renal corpuscle, the proximal and convoluted tubules, the loop of Henle, and the collecting ducts. And while we're in the neighborhood, we'll make mention of some of the echo. extra renal systems, and vascular supply to the kidney. We'll also, of course, as is my usual practice, talk about some of the medical applications of what we're learning today. So, in brief, the functions of the kidney are as follows. Of course, we're all familiar with the ability of the kidney to rid the body of nitrogenous waste, which are the products of... protein catabolism. And without kidney, of course, somebody has to stay a long time on dialysis or get a kidney transplant. And this is done to get rid of the waste products, such as urea, uric acid, ammonia, and some of the other byproducts of metabolism. As well, the kidney is very much involved in regulating fluid and electrolyte balance. And because Because it does that, it's also involved in blood pressure regulation. Finally, there are several discrete hormones produced by the kidney, including erythropoietin, which is involved in blood cell formation. So the gross anatomy goes basically like this. As with many abdominal organs and thoracic organs, there's a tough, utter capsule of compulsive connective tissue against a dense, irregular membrane around... the kidney and we refer to the various poles of the kidney based on whether they're towards the top or bottom so towards the head is the superior pole sometimes called the the cephalic pole, and the caudal pole, or the inferior pole. Now, like many organs, the kidney is divided into constituent parts, a cortex and an inner medulla. There's an indentation through which major vessels enter and leave, called the renal hilum. And unlike many organs, it is one of the retroperitoneal organs, which means that it's not suspended by mesentery. Rather, it's loosely held against the posterior body wall by means of the parietal peritoneum. So, a few other things to note while we're looking at the gross anatomy. There is essentially a hollow area in the kidney right next to the hilum called the renal pelvis. And it's into the pelvis that, of course, urine drains, coming first from smaller tributaries called minor calyces, through larger tributaries called major calyces. into the pelvis and finally out of the kidney by means of a ureter. You'll also note a few fairly obvious structures even on the prosected specimen, the side here. You'll note that there are essentially pyramidal-shaped tracts called renal pyramids, and this is an important area where some of the loops of Henle in collecting dex course, and the end in renal papillae. And each of these little pyramids can be considered a renal lobe. As well, there's a lot of perinephric fat, or unilocular fat, found in and around the hilum, extending deeper into the tissue of the kidney through what are known as renal sinuses. And as well, there's a lot of perinephric fat, or unilocular fat, found in and around Well, there is, of course, a very vigorous blood supply coming in via the renal artery and leaving via the renal vein. If we look at one of those kidney lobules a little bit... in a little bit more detail, you'll notice the following. What's depicted here are the functional units of the kidney, which are called the nephrons, and they're essentially two types. One, which has the bulk of its tubular portion in the cortex, called cortical nephrons, and another which has got a deeper portion of the loop family going deeper into the substance of the kidney, into the medulla, called juxtamedullary nephrons. There are a few other differences as well. Renal corpuscles of the cortical nephrons tend to be higher up in the cortex. The juxtamedullary ones have their renal corpuscles close to the closer to the interstices of the cortex, the medulla. And as well, if you look at the loop of Henle, and that's a structure we'll talk about in a little bit more detail, you'll see that the loop of Henle here has got a very long, thin section or portion. which ascends deep into the medulla. Whereas if you compare the loop of Henle of the cortical nephrons, they have a relatively speaking short thin limb of loop of Henle. This has some functional consequences, and for reasons that will become apparent a little later on, I hope, these juxtamodulary nephrons have got much greater concentrating power when it comes to forming urine filtrate. What's shown... shown at the end of these collecting ducts through which the final urine filtrate is formed is small openings in a structure called the renal papilla. These little openings are ducts are called papillary ducts. You can also see part of the circulatory system here in the kidney. We have various branches of the renal artery ultimately forming arcuate vessels which are found right at the junction of the cortex medulla and these send out interlobular and interlobar branches and ultimately form tributaries which comprise the glomerulus which is a capillary found in the renal corpuscle, and we'll talk more about that shortly. So this shows you essentially what I was talking about, but it highlights some of the circulatory structures a little better. So again, we have branches of the renal artery, which dive into larger interlobar arteries, and then smaller interlobular arteries, and around here you have those arcuate arteries. Again, cortical and juxtamedullary nephrons, the juxtamedullary nephrons being the better concentrators of urine, and they have these very long thin limbs of lupafenly. There are a few other structures to mention as well that we haven't talked about yet. Each nephron consists of a Bowman's capsule and glomerulus called the renal corpuscle here. And here I'm showing you a cortical nephron, followed by various tubular sections, which we'll show in more detail in later slides. But what this slide also does show you is essentially the route that some of the circulatory system takes in the kidney. And we'll talk about different parts of the circulatory supply of the nephron. But you'll see... that essentially what happens is urine filtrate goes in this direction down a descending limb and up an ascending limb of the loop of Henle. And following that is what's called a peritubular capillary network. And branches of that are called the vasorecta. And we'll talk about the vasorecta a little later on, but the vasorecta is essentially what takes away some of the resorbed material from urine filtrate. So... The nephron itself needs to be talked about before I show you some of the structures. Each part of the nephron, no surprise, is specialized. The renal corpuscle is really ideally specialized for the production of ultrafiltrate. And that ultrafiltrate production is driven mainly by blood hydrostatic pressure. So blood hydrostatic pressure, which is the pressure any fluid has on the walls of its container, forces blood out or components. components of blood out of the glomerulus and into the first hollow part of the nephron called the Bowman's capsule. And we'll deal with that in a bit more detail. The rest of the nephron is specialized to modify what's initially filtered. What's initially filtered at the Bowman's capsule is really equiosmolar with blood, it's around 300 milliosmolar, but then it gets modified greatly by the tubular portion. And some of the functions that are involved include secretion, reabsorption, and then and water conservation. And what's interesting to note is that about 180 liters of ultrafiltrates produced every day in a person with two functional kidneys, but only one to two liters of urine is formed. So there's a lot of reabsorption and water conservation that goes on. So let's start with the first part of the nephron, which is called the renal corpuscle. And that consists of the glomerulus, which is a tuft of specialized capillaries, and a tubular structure which surrounds it called Bowman's capsule. And the renal corpuscle is a vascular pole and a urinary pole. And the vascular pole is the one through which an artery, arteriole, called the afrin arteriole, enters. And the urinary pole is the part, of course, from which urine flows. So it's essentially, a Bowman's capsule that is, it's essentially a modified cupped version of a blind epithelial tube. And it has an outer layer of cells and an inner layer of cells. layer, the parietal layer, and we've talked about the parietal layer in earlier lectures, and between the parietal and visceral layers is a Bowman's urinary space. You may recall us talking about the visceral layer of Bowman's capsule, which consists of podocytes. And we'll show you some pictures of that shortly. The glomerulus is essentially, as I mentioned, a tuft of capillaries. And these are very fenestrated, meaning, of course, they've got fairly wide slits between adjacent endothelial cells. And it's created... created by means of an arteriole which comes in, forms the capillary, the glomerulus, and then comes out. So the part that goes in is called the afferent arteriole, the part that comes out is called the efferent arteriole. And the muscles in the capillary are called the glomerulus. and these arterioles are under autonomic control. Typically, the efferent arteriole has a smaller diameter, and the significance of that is something we'll talk about shortly. There are also some specialized cells called mesangial cells, which you'll see in a diagram, which are essentially phagocytes and also contractile, so they can actually essentially massage, filtrate through. And there's also special basal lamina, which... deserves mentioning. So here is a diagram, a very simplified diagram, of a renal corpuscle. And you see here the afferent arteriole coming in, forming this fenestrated capillary called the glomerulus, and then blood leaves by means of an efferent arteriole. And the way I remember that is to think of E for exit. And essentially what drives this filtration process is blood hydrostatic pressure. pressure. So blood hydrostatic pressure is greater than the pressure inside the capillary, inside the glomerulus itself, so then it forces a movement out of the glomerulus and into the Bowman space. And there's a driving pressure of around 10 mmHg, which accomplishes that. So a lot of things get filtered. There's only fairly gross differentiation between products that do get filtered. And that really depends on, what gets filtered depends on the nature of the barrier between the glomerulus and Bowman's capsule. This is an... light microscope view showing you some of the structures I was talking to you about. This is Bowman's space here. This would be the parietal wall. The visceral wall is tough to distinguish. And what you see here is essentially the capillary, which is sort of winding around in a tight ball. And the visceral wall is composed of these special cells called podocytes, which you'll see a little bit better. There are also mesangial cells shown here. And a A few other structures that are worth noting, there are some extraclomerular mesangial cells, again mainly phagocytic and contractile, and a specialized area called the macula densa, and we'll talk about that shortly. An EM view of a portion of the glomerulus looks like this. So here you see an endothelial cell, and this is the nucleus of course, and that endothelial cell is the endothelial cell. cell, which is a single cell layer which comprises the glomerular capillary. It's surrounded by podocytes, which send out little foot processes or pedicels. And if you look at this area right here, what you'll see are some unique structures. You'll see these podocytes, a basement membrane, and then this very fenestrated glomerular epithelium. And if you look a little closer, what you'll see is this. You see essentially a trilaminar basement membrane. We'll talk about that in another picture. And here we see foot processes and this fenestrated epithelium of the glomerulus. So essentially there are some fairly gross filtration slits through which large proteins can pass, but not things like red blood cells, say. And then the basement membrane, which does delimit further what some of the things are that can pass. And it's really a mechanical filtration device. as well as a charge filtration device. And there are essentially two parts, sorry three parts of this basal lamina. If you look at it here you'll see again a trilaminar basal lamina, there's a lamina densa on either side and a lamina rara sort of in the middle. So the dense is denser than the rara. And what you'll also notice is that these podocytes here are filled with actin, and no surprise perhaps to most of you, are bound to the basal lamina by means of integrins. And furthermore, stabilizing the whole structure is a protein called nephrin, which links adjacent foot processes. We'll go up or down a magnification and look at this again. Again, here's this trilaminar basal lamina, these foot processes, and these fenestrations. And there's a charge in the basal lamina, as well as charges on the various fenestrated branches of the endothelium, which can... repel certain proteins. So a cation is a positive charge, an anion is a negative charge. So these anionic charges would repel things which are materials which are also negatively charged. In some disease states we can get autoimmune disorders which involve autoantibodies which essentially attack various parts of this filtration barrier. For example... Good Pasteur Syndrome involves the formation of autoantibodies to the basal lamina that you find in the kidneys. Still other diseases involve fairly nonspecific inflammatory processes at the level of the filtration apparatus of the kidney. And glomerulonephritis is a disorder which involves an inflammation of the glomeruli. If we look at an SEM view, you'll see, or gain a little bit better appreciation of what these podocytes, which are part of the visceral wall of Bowman's capsule, actually look like. Here you can see the podocyte cell body and the numerous, numerous branching processes. And if you take those away, those protocytes away, you can actually see these multiple little indentations in the glomerular membrane, which shows you just how much these little foot processes interdigitate with endothelial cells and are intimately linked. And to put some of the structures I showed you earlier in broader perspective, here's a renal corpuscle. We have an afferent arteriole going in, an efferent arteriole going out, and I mentioned there's a functional significance to that. have a larger afferent arteriole and a smaller efferent, of course we'll have greater flow through the afferent and less flow through the efferent, which will ultimately generate more pressure in the glomerular membrane. And that will aid in the... the filtration of materials from blood into the Bowman space. I also mentioned that there's a special area called the macula densa. And what's interesting, and a little hard to get your head around perhaps, is the fact that there's a specialized zone of the macula densa, or sorry, a specialized zone of the distal convoluted tubule, which actually forms the macula densa, and it comes right up to a very highly modified area of the acromartyrial called the juxtaglomerular cells. So the juxtaglomerular cells and the macula densa of the distal convoluted tubule together comprise the juxtaglomerular apparatus. All right, then we'll turn to that more in a bit. Coming away from the renal corpuscle, of course, we get into the tubular portion of the nephron, which consists of a proximal convoluted tubule. Lupapenly, which has got thick and thin portions, distal convoluted tubule, and a collecting duct, which ends in papillary pores, and is the means by which urine ultimately goes into the renal pelvis. Now, you'll note... that at the side are pictured various cells. And these cells are representative of different parts of the tubular portion of the nephron, and they're quite different. You notice that cells in the proximal convolvulus I've got a highly enfolded apical surface, a few basal folds, and lots and lots of mitochondria, so I don't really have to tell you what that means. Likewise, in distal convoluted tubules, there are also lots of mitochondria, even more basal enfoldings, but relatively few apical enfoldings. The thin loop of Henle is more squamous, again with lots of mitochondria, whereas the... See, collecting duct cells are relatively devoid of invaginations or evaginations, and have a few scattered mitochondria and other intracellular organelles. So let's start with the proximal convoluted tubule first. They're essentially cuboidal, as you saw in the picture on the other slide. They've got a very prominent brush border. They have, not as easily seen in the previous diagram, but they have lots of... lateral plasma membrane interdigitations. They've also got quite a few basal enfoldings in the mitochondria. And we have lots and lots of ion channels and pumps, especially the sodium-potassium pump along the basal portion. And the main functions of proximal convoluted tubule are actually pretty significant. It's a primary place for ion reabsorption, some water reabsorption. It's where we take in amino acids, sugars, and certain proteins. And when you look in a lab under a microscope with a fairly high view, what you'll see is this. You'll see a cross-section of the proximal convolute tubule. And this lighter staining portion here of these cuboidal cells is the brush border. So lots and lots of microvilli. You'll notice right beside it the distal convoluted tubule and what you don't see is a significant brush border. Turning back to the proximal convoluted tubule, here are some of those basal infoldings I told you about and they seem a little darker because they've got lots and lots of mitochondria in them. And here's an EM view, which again shows you some of the same thing. Here is the basal border with a capillary right next to it, and you see quite a few infoldings with mitochondria. So time for a little histophysiology. I mentioned that's a place where ions are reabsorbed, and those are glucose molecules, amino acids, and other large molecules like peptides. So to do that, of course, we have to have very distinct apical and basolateral domains. And we do that by means of tight junctions. We've got antiporters such as proton sodium. antiporters which allow sodium to cross in and leave by means of sodium channels in the lateral membrane and recall I talked about the sodium potassium pump kicks 3 sodium out 2 potassium in and that generates a low sodium gradient which is what essentially powers the sodium movement through these cells as well we've got various glucose transporters and we We talked about the glute transporters before when we were discussing glucose movement. And so we've got several different types of glucose transporters which allow glucose to enter apically and glucose permeases which allow glucose to leave basally. And so it's perhaps not surprising that you would see lots of mitochondria, lots of membrane elaborations. As well peptides get transported by. by transcytosis across and as they are being transported some of them get broken down by lysozymes which you find. So at the end of the day where all these materials go once they come from the lumen and leave the basal surface, well they are picked up by a very intricate capillary network which surrounds the lumen. proximal and distal convoluted tubules. The loop of Henle is a thin portion, mainly thin, but has also thick limbs which are similar to the proximal and distal convoluted tubules. While the thin limb, which and juxtamedullary nephrons is really the most extensive part of the lupine family, we see the epithelium being comprised of a simple squamous epithelium. And the descending limb... that is the one that comes from the proximal convoluted tubule and to the medulla, is decidedly more permeable to water. And this allows what's known as the countercurrent exchange system to work. The ascending limb, by comparison, is relatively less permeable to water, but has got lots of sodium and chloride and potassium transporters. If we look at an EM view, you can see here the thin limb of a loop of Henle in sort of an oblique section as it's leaving a portion of the proximal tubule of the nephron. Light micrograph view, you can pick out some of the distal convoluted tubules and collecting ducts, but also the thin limbs of the loop of Henle, which you can see right here. So here's a thin limb, a squim. epithelium here you can see various capillaries scattered around but of course there's less cytoplasm they stain less densely so see if you can spot those squamous epithelial cells which form the walls the loop of Henle. And as I mentioned, there's an intricate vascular network, and you can see this really well here. Right next to this thin wall of loop of Henle, you can see a capillary. And the capillary and the loop of Henle actually share some of the same basal lamina. Okay, so I mentioned something called the vasorecta a little earlier, and the vasorecta is really part of the peritubular capillary network which surrounds and supplies the capillary network. the nephron and there's a branch which goes follows along with the loop of Henle and then one which leaves and ascends as well as not pictured in the slide there are several sort of connecting loops between the descending and ascending part of the vasorecta. The vasorecta is really involved in picking up a lot of the materials which are reabsorbed from the kidney. You can see some of the vasorecta here in this diagram. Now I don't expect to be able to see it really easily in your particular histological preps. So if you look at thin and thick limbs of the lupus henlii, they're fairly obviously different. Here you see a descending thin limb, squamous epithelial cells. an ascending thick limb of the loop of Henle, more cuboidal, lots of mitochondria, because they are ion pumpers, as I mentioned, and then these spaces here, which are part of the vasorecta, very closely applied to the loop of Henle. I mentioned a countercurrent multiplier, and the way it works is essentially this. So, I mentioned that the descending limb of the loop appendix is pretty water permeable. And the ascending limb is really specialized for ion pumping. So essentially what happens is this. Ions are pumped out of the ascending limb. That makes a very salty and... environment in the interstitium surrounding the loop of Henle, that will osmotically attract water, and that water gets picked up and transported away, water and ions get picked up and transported away continuously by the vasorecta. So, essentially what happens is, filtrate starts off being about equally osmolar with blood, around 300 milliosmolar, and it gets... more and more concentrated as water leaves. So it's around 1,200... milliosmolar at the bottom of the loop of Henle, and then because we're pumping ions out, it gets progressively more and more hypoosmotic. So essentially we go from being iso to hyper to... hypoosmotic as we course through. Eventually when we get to the top of the proximal convolutubule it gets more eukaryoteosmolar. This whole process kind of reverses as we go out to collecting duct which you can see here. Because we've got a very salty interstitium here, it's going to draw water out. So a lot of water moves out of the collecting duct by means of water channels. And that gets picked up again by the vasorecta and returned to the blood. vascular supply. So the distal convoluted tubule is again cuboidal epithelium. It has fewer short microvilli, but compared to proximal convoluted tubule, it has an extensive basal plasma membrane with lots of mitochondria, lots of potassium pumps, and other ion transporters. And essentially, they will drain into collecting ducts. And in this particular image, you can see a proximal and distal conflux of tubules again. And this isn't perhaps as good, but this would be one of the previous ones I showed you. But here you can see a distal conflux of tubule, proximal next to it. And not as easily seen, but you can see there's more material here, it's slightly lighter stained, than the rest of the cell would be the brush border of a proximal convoluted tubule. And you'll see blood vessels and whatnot and thin limbs of loops of henle mixed in. So to compare proximal and distal convoluted tubule epithelial cells, this is a great diagram. It shows you essentially the main difference, two main, three main differences. Proximal convoluted tubule cells are a little taller. have taller microvilli and the basal surface is not quite as convoluted whereas it's more convoluted in the distal convoluted tubule shorter cells shorter sparser microvilli So, time for a little histophysiology of the distal convoluted tubule. And, again, there is some reabsorption that occurs here. Sodium and chloride, amongst other things, get reabsorbed. This is under the control of a couple of... of hormones, but the main one to note is aldosterone, and aldosterone is a product of the adrenal glands, the adrenal cortex in particular, and it upregulates sodium channels as well as upregulates sodium-potassium pumps. So that allows some of the fine-tuning of sodium chloride transport. Now, I mentioned the juxtaculomereular apparatus, which consists of juxtaculomereular cells and the macula densa. It's at the vascular end of the renal corpuscle. Starting with the juxtaculomary cells, these are really modified afferent smooth muscle cells which have got renin in them. So you'll see some renin granules. As I mentioned earlier, the macula densa are really modified distal convoluted tubules. cells that are sensitive to tubular chloride and sodium. Essentially you have to think of the distal convoluted tubule cells as being twisted around to be close to the juxtaglomerular cells. And this shows you a juxtaglomerular cell of the afro-arterial. And there are lots of granules in here which contain renin. And we'll talk about renin very briefly. Essentially. low blood pressure in the afferent arteriole causes renin to be released that reacts with angiotensinogen to make angiotensin 1 and that's converted by angiotensin converting enzymes into angiotensin Angiotensin II has got a couple of rules, yet amongst other things acts as a vasoconstrictor. So that means it raises blood pressure, but it also upregulates aldosterone from the adrenal cortex. And aldosterone causes the kidney to retain water and sodium mainly by upregulating sodium transport molecules. If you increase sodium reabsorption, you increase the amount of sodium in the blood water is going to follow. As well, I mentioned one of the endocrine functions of the kidney, that is the release of erythropoietin. That's really primarily juxtacomero cells, which release EPO, or erythropoietin, and that stimulates bone marrow cells to make red blood cells. You may have heard of athletes doping. They can dope in a couple of different ways, of course, but endurance athletes, such as cyclists, have been caught using erythropoietin, which the kidneys normally make, and that is used to stimulate their bone marrow to produce more red blood cells. And of course, with more red blood cells, you've got higher oxygen carrying capacity. Now, let's look at the structure of the juxtaculomary cells, or the positioning of the juxtaculomary cells relative to the macula densa. So again, juxtaculomary cells are modified smooth muscle cells of the afferent arteriole. So here's the afferent. arteriole here and clustered in this area is our juxtaglomerular cells these mesangial cells which are essentially phagocytes and are contractile and the mesangial cells are the mesangial cells. macula densa and together the macula densa which is sensitive to chloride but also to sodium and the dexamera cells which are sensitive to blood pressure together collaborate in the release of renin and this shows you in a bit more detail what I was just talking about so the Cells of the distal convolutubule, which comprise the macula densa or dense body, sense changes in sodium and chloride. And cells of the juxtaglomerular apparatus sense changes in blood pressure. Together, they collaborate in renin release. Renin and plasma converts angiotensinogen into angiotensin I. And then, enzymes called angiotensin-converting enzymes, change it to angiotensin II, which in turn is a potent vasoconstrictor, but also upper-regulates aldosterone from the adrenal cortex. And aldosterone functions mainly at the distal convoluted tubule, and together, the enhanced sodium uptake and vasoconstriction increase blood pressure. Now, understanding this is not just a moot point. It's kind of cool because... This led to the development of several very useful tools in the toolbox that's used for treating hypertension. So for example, there are a couple of classes of enzymes such as the angiotensin converting enzyme inhibitors or ACE inhibitors, which block the transformation of angio-1 into angio-2. And so we... So we use drugs such as Valsartan or Candasartan, and these are, I'm sorry, I beg your pardon, I got a little ahead of myself. We use drugs like Captopril, which is an angiotensin converting enzyme inhibitor to prevent angiotensin 2 from being formed. So anytime you hear a pril at the end of a drug name, it's probably an ACE inhibitor. And as well, Because we know that angiotensin 2 is a potent vasoconstrictor, we've also got angiotensin receptor blockers, or ARBs. And examples of ARBs are drugs like Valsartan and Candasartan. So PRILs are ACE inhibitors, so Captopril would block this step here. Whereas angiotensin receptor blockers, or ARBs, such as Valsartan, Sartan and Cantosartan will block this here. Alright, and just to prove to you I'm not making all this up, here would be of course the renal corpuscle with the bone in space, glomerulus here, and afro-arterial would be someplace in this vicinity, but here this little row of cells is the macula densa. So look closely at your lab specimens and you should be able to find some of these. And this shows you a diagram of what I was just talking about. Afrin arteriole, effrin arteriole, afrin's larger than effrin, it's going to boost blood pressure and the glomerulus enhance filtration. as well as juxtaglomerular cells, macula densa, and mesangial cells. So together, the juxtaglomerular cells and macula densa sense changes in pressure and osmolarity and cause renin to be released. On our trip through the kidney, of course, we're going to end up eventually in the collecting tubules. And these essentially function to transport filtrate. to papillae and medulla and cortical and medullary collecting tubules both end up at these papilla and they have a couple specialized cell types, principal cells and intercalated cells. The principal cells have relatively few mitochondria, just a few short microvilli with a few basal plasma enfoldings. So we're not really sure what the functions are. The intercalated cells have got a plasma membrane with microplicae, lots of apical vesicles, a bunch of abundant mitochondria, and they're more involved in hydrogen ion secretion. Collectively, though, the cells of the collecting tubules can be manipulated to enhance water movement. And this is done by means of a hormone called vasopressin, or antidiuretic hormone. And what ADH does is cause the insertion of water channels called aquaporins, and you can read about that in your text. into the plasma membrane and this makes it easier for water to follow sodium out of the tubules and into the interstitial area of the nephron and from thence into the vasorecta And this shows you some of the cells of the collecting tubular, and you see intercalated cells and principal cells. And so we think that intercalated cells secrete either protein or protein. Protons are bicarb and may be involved in potassium reabsorption. The principal cells are also thought to be involved in sodium transport and water and secreting. potassium, although we're not totally sure about which does what. The aldosterone that I mentioned coming from the adrenal cortex is what stimulates the reabsorption of sodium here, but it's mainly vasopressin or ADH which is involved in water transport. We're getting close to the end here. The urinary tract really begins with the renal calyces and renal pelvis. So once urine filtrate is finished off and formed, and we're dealing with a hyperosmolar filtrate, usually around 12. 1200 to 1400 milliosmoles compared to about 300 milliosmolar in blood. And this drains from the calyces into the pelvis and then out of the ureter and into the bladder. The last few things I'd like to do is compare the layers of the ureter and bladder and their epithelial lining. We'll pay special attention to the transitional epithelium, which you've identified before in the lab exam, but we're going to talk a bit more about some of its finer structure. So here are pelvic calyces, which eventually... empty into the ureter. And the ureter, like the kidney, also has a transitional epithelium. It's quite highly enfolded, but can stretch. So there's a mucosal layer here, from here to here. There's a muscularis and a cirrhosa or aphantasia around the whole thing. And it can increase in diameter to facilitate flow. Right underneath this transitional epithelium is the lamina propria. So together... together the transitional epithelium and the lamina propria, which is a vascular connective tissue area, make the mucosa. And you can convince yourself this is a transitional epithelium again by looking at the nuclei of the cells in the unstretched ureter. And you can see that they're nice and large and rounded, just as they would be here, towards the bottom. And this helps you distinguish it from, say, a stratified squamous epithelium, because these cells... the luminal side or anything but squamous. And you all know that the bladder has a transitional epithelium, which allows stretching. And so these big folds of transitional epithelium in the unstretched bladder come with this connective tissue of the lamina propria. And when they... the bladder is filled with urine, of course, that all stretches. Now, there's a few more details about the transitional epithelium which are worth knowing. There is a very unique specialization of the transitional epithelium in the bladder, which include these little plaques. And these apical plaques are really basically aggregates of intramembrane proteins, and they're anchored to cytoskeletal proteins on these cells, so that when the bladder stretches, the transitional epithelium, of course, stretches, and... the luminal cells flatten out, but there are plaques, these plaques here, which help anchor the apical regions of the cells together. So it's a very fibroelastic conglomeration of cytoskeletal proteins, which allows stretching. And with that, that ends our trip through renal structures. If you have any questions, please let me know.

We'll focus primarily on the structure of the nephron, which is the major functional unit. unit of the kidney. And this includes the following constituent parts, the renal corpuscle, the proximal and convoluted tubules, the loop of Henle, and the collecting ducts.

And while we're in the neighborhood, we'll make mention of some of the echo. extra renal systems, and vascular supply to the kidney. We'll also, of course, as is my usual practice, talk about some of the medical applications of what we're learning today. So, in brief, the functions of the kidney are as follows.

Of course, we're all familiar with the ability of the kidney to rid the body of nitrogenous waste, which are the products of... protein catabolism. And without kidney, of course, somebody has to stay a long time on dialysis or get a kidney transplant.

And this is done to get rid of the waste products, such as urea, uric acid, ammonia, and some of the other byproducts of metabolism. As well, the kidney is very much involved in regulating fluid and electrolyte balance. And because Because it does that, it's also involved in blood pressure regulation. Finally, there are several discrete hormones produced by the kidney, including erythropoietin, which is involved in blood cell formation.

So the gross anatomy goes basically like this. As with many abdominal organs and thoracic organs, there's a tough, utter capsule of compulsive connective tissue against a dense, irregular membrane around... the kidney and we refer to the various poles of the kidney based on whether they're towards the top or bottom so towards the head is the superior pole sometimes called the the cephalic pole, and the caudal pole, or the inferior pole. Now, like many organs, the kidney is divided into constituent parts, a cortex and an inner medulla. There's an indentation through which major vessels enter and leave, called the renal hilum.

And unlike many organs, it is one of the retroperitoneal organs, which means that it's not suspended by mesentery. Rather, it's loosely held against the posterior body wall by means of the parietal peritoneum. So, a few other things to note while we're looking at the gross anatomy.

There is essentially a hollow area in the kidney right next to the hilum called the renal pelvis. And it's into the pelvis that, of course, urine drains, coming first from smaller tributaries called minor calyces, through larger tributaries called major calyces. into the pelvis and finally out of the kidney by means of a ureter.

You'll also note a few fairly obvious structures even on the prosected specimen, the side here. You'll note that there are essentially pyramidal-shaped tracts called renal pyramids, and this is an important area where some of the loops of Henle in collecting dex course, and the end in renal papillae. And each of these little pyramids can be considered a renal lobe.

As well, there's a lot of perinephric fat, or unilocular fat, found in and around the hilum, extending deeper into the tissue of the kidney through what are known as renal sinuses. And as well, there's a lot of perinephric fat, or unilocular fat, found in and around Well, there is, of course, a very vigorous blood supply coming in via the renal artery and leaving via the renal vein. If we look at one of those kidney lobules a little bit... in a little bit more detail, you'll notice the following. What's depicted here are the functional units of the kidney, which are called the nephrons, and they're essentially two types.

One, which has the bulk of its tubular portion in the cortex, called cortical nephrons, and another which has got a deeper portion of the loop family going deeper into the substance of the kidney, into the medulla, called juxtamedullary nephrons. There are a few other differences as well. Renal corpuscles of the cortical nephrons tend to be higher up in the cortex.

The juxtamedullary ones have their renal corpuscles close to the closer to the interstices of the cortex, the medulla. And as well, if you look at the loop of Henle, and that's a structure we'll talk about in a little bit more detail, you'll see that the loop of Henle here has got a very long, thin section or portion. which ascends deep into the medulla.

Whereas if you compare the loop of Henle of the cortical nephrons, they have a relatively speaking short thin limb of loop of Henle. This has some functional consequences, and for reasons that will become apparent a little later on, I hope, these juxtamodulary nephrons have got much greater concentrating power when it comes to forming urine filtrate. What's shown... shown at the end of these collecting ducts through which the final urine filtrate is formed is small openings in a structure called the renal papilla. These little openings are ducts are called papillary ducts.

You can also see part of the circulatory system here in the kidney. We have various branches of the renal artery ultimately forming arcuate vessels which are found right at the junction of the cortex medulla and these send out interlobular and interlobar branches and ultimately form tributaries which comprise the glomerulus which is a capillary found in the renal corpuscle, and we'll talk more about that shortly. So this shows you essentially what I was talking about, but it highlights some of the circulatory structures a little better.

So again, we have branches of the renal artery, which dive into larger interlobar arteries, and then smaller interlobular arteries, and around here you have those arcuate arteries. Again, cortical and juxtamedullary nephrons, the juxtamedullary nephrons being the better concentrators of urine, and they have these very long thin limbs of lupafenly. There are a few other structures to mention as well that we haven't talked about yet. Each nephron consists of a Bowman's capsule and glomerulus called the renal corpuscle here.

And here I'm showing you a cortical nephron, followed by various tubular sections, which we'll show in more detail in later slides. But what this slide also does show you is essentially the route that some of the circulatory system takes in the kidney. And we'll talk about different parts of the circulatory supply of the nephron.

But you'll see... that essentially what happens is urine filtrate goes in this direction down a descending limb and up an ascending limb of the loop of Henle. And following that is what's called a peritubular capillary network. And branches of that are called the vasorecta.

And we'll talk about the vasorecta a little later on, but the vasorecta is essentially what takes away some of the resorbed material from urine filtrate. So... The nephron itself needs to be talked about before I show you some of the structures.

Each part of the nephron, no surprise, is specialized. The renal corpuscle is really ideally specialized for the production of ultrafiltrate. And that ultrafiltrate production is driven mainly by blood hydrostatic pressure.

So blood hydrostatic pressure, which is the pressure any fluid has on the walls of its container, forces blood out or components. components of blood out of the glomerulus and into the first hollow part of the nephron called the Bowman's capsule. And we'll deal with that in a bit more detail.

The rest of the nephron is specialized to modify what's initially filtered. What's initially filtered at the Bowman's capsule is really equiosmolar with blood, it's around 300 milliosmolar, but then it gets modified greatly by the tubular portion. And some of the functions that are involved include secretion, reabsorption, and then and water conservation.

And what's interesting to note is that about 180 liters of ultrafiltrates produced every day in a person with two functional kidneys, but only one to two liters of urine is formed. So there's a lot of reabsorption and water conservation that goes on. So let's start with the first part of the nephron, which is called the renal corpuscle. And that consists of the glomerulus, which is a tuft of specialized capillaries, and a tubular structure which surrounds it called Bowman's capsule.

And the renal corpuscle is a vascular pole and a urinary pole. And the vascular pole is the one through which an artery, arteriole, called the afrin arteriole, enters. And the urinary pole is the part, of course, from which urine flows.

So it's essentially, a Bowman's capsule that is, it's essentially a modified cupped version of a blind epithelial tube. And it has an outer layer of cells and an inner layer of cells. layer, the parietal layer, and we've talked about the parietal layer in earlier lectures, and between the parietal and visceral layers is a Bowman's urinary space.

You may recall us talking about the visceral layer of Bowman's capsule, which consists of podocytes. And we'll show you some pictures of that shortly. The glomerulus is essentially, as I mentioned, a tuft of capillaries. And these are very fenestrated, meaning, of course, they've got fairly wide slits between adjacent endothelial cells. And it's created...

created by means of an arteriole which comes in, forms the capillary, the glomerulus, and then comes out. So the part that goes in is called the afferent arteriole, the part that comes out is called the efferent arteriole. And the muscles in the capillary are called the glomerulus.

and these arterioles are under autonomic control. Typically, the efferent arteriole has a smaller diameter, and the significance of that is something we'll talk about shortly. There are also some specialized cells called mesangial cells, which you'll see in a diagram, which are essentially phagocytes and also contractile, so they can actually essentially massage, filtrate through. And there's also special basal lamina, which... deserves mentioning.

So here is a diagram, a very simplified diagram, of a renal corpuscle. And you see here the afferent arteriole coming in, forming this fenestrated capillary called the glomerulus, and then blood leaves by means of an efferent arteriole. And the way I remember that is to think of E for exit. And essentially what drives this filtration process is blood hydrostatic pressure.

pressure. So blood hydrostatic pressure is greater than the pressure inside the capillary, inside the glomerulus itself, so then it forces a movement out of the glomerulus and into the Bowman space. And there's a driving pressure of around 10 mmHg, which accomplishes that. So a lot of things get filtered.

There's only fairly gross differentiation between products that do get filtered. And that really depends on, what gets filtered depends on the nature of the barrier between the glomerulus and Bowman's capsule. This is an... light microscope view showing you some of the structures I was talking to you about.

This is Bowman's space here. This would be the parietal wall. The visceral wall is tough to distinguish. And what you see here is essentially the capillary, which is sort of winding around in a tight ball.

And the visceral wall is composed of these special cells called podocytes, which you'll see a little bit better. There are also mesangial cells shown here. And a A few other structures that are worth noting, there are some extraclomerular mesangial cells, again mainly phagocytic and contractile, and a specialized area called the macula densa, and we'll talk about that shortly. An EM view of a portion of the glomerulus looks like this.

So here you see an endothelial cell, and this is the nucleus of course, and that endothelial cell is the endothelial cell. cell, which is a single cell layer which comprises the glomerular capillary. It's surrounded by podocytes, which send out little foot processes or pedicels. And if you look at this area right here, what you'll see are some unique structures. You'll see these podocytes, a basement membrane, and then this very fenestrated glomerular epithelium.

And if you look a little closer, what you'll see is this. You see essentially a trilaminar basement membrane. We'll talk about that in another picture. And here we see foot processes and this fenestrated epithelium of the glomerulus. So essentially there are some fairly gross filtration slits through which large proteins can pass, but not things like red blood cells, say.

And then the basement membrane, which does delimit further what some of the things are that can pass. And it's really a mechanical filtration device. as well as a charge filtration device. And there are essentially two parts, sorry three parts of this basal lamina. If you look at it here you'll see again a trilaminar basal lamina, there's a lamina densa on either side and a lamina rara sort of in the middle.

So the dense is denser than the rara. And what you'll also notice is that these podocytes here are filled with actin, and no surprise perhaps to most of you, are bound to the basal lamina by means of integrins. And furthermore, stabilizing the whole structure is a protein called nephrin, which links adjacent foot processes. We'll go up or down a magnification and look at this again.

Again, here's this trilaminar basal lamina, these foot processes, and these fenestrations. And there's a charge in the basal lamina, as well as charges on the various fenestrated branches of the endothelium, which can... repel certain proteins.

So a cation is a positive charge, an anion is a negative charge. So these anionic charges would repel things which are materials which are also negatively charged. In some disease states we can get autoimmune disorders which involve autoantibodies which essentially attack various parts of this filtration barrier.

For example... Good Pasteur Syndrome involves the formation of autoantibodies to the basal lamina that you find in the kidneys. Still other diseases involve fairly nonspecific inflammatory processes at the level of the filtration apparatus of the kidney.

And glomerulonephritis is a disorder which involves an inflammation of the glomeruli. If we look at an SEM view, you'll see, or gain a little bit better appreciation of what these podocytes, which are part of the visceral wall of Bowman's capsule, actually look like. Here you can see the podocyte cell body and the numerous, numerous branching processes. And if you take those away, those protocytes away, you can actually see these multiple little indentations in the glomerular membrane, which shows you just how much these little foot processes interdigitate with endothelial cells and are intimately linked. And to put some of the structures I showed you earlier in broader perspective, here's a renal corpuscle.

We have an afferent arteriole going in, an efferent arteriole going out, and I mentioned there's a functional significance to that. have a larger afferent arteriole and a smaller efferent, of course we'll have greater flow through the afferent and less flow through the efferent, which will ultimately generate more pressure in the glomerular membrane. And that will aid in the... the filtration of materials from blood into the Bowman space.

I also mentioned that there's a special area called the macula densa. And what's interesting, and a little hard to get your head around perhaps, is the fact that there's a specialized zone of the macula densa, or sorry, a specialized zone of the distal convoluted tubule, which actually forms the macula densa, and it comes right up to a very highly modified area of the acromartyrial called the juxtaglomerular cells. So the juxtaglomerular cells and the macula densa of the distal convoluted tubule together comprise the juxtaglomerular apparatus. All right, then we'll turn to that more in a bit. Coming away from the renal corpuscle, of course, we get into the tubular portion of the nephron, which consists of a proximal convoluted tubule.

Lupapenly, which has got thick and thin portions, distal convoluted tubule, and a collecting duct, which ends in papillary pores, and is the means by which urine ultimately goes into the renal pelvis. Now, you'll note... that at the side are pictured various cells. And these cells are representative of different parts of the tubular portion of the nephron, and they're quite different.

You notice that cells in the proximal convolvulus I've got a highly enfolded apical surface, a few basal folds, and lots and lots of mitochondria, so I don't really have to tell you what that means. Likewise, in distal convoluted tubules, there are also lots of mitochondria, even more basal enfoldings, but relatively few apical enfoldings. The thin loop of Henle is more squamous, again with lots of mitochondria, whereas the...

See, collecting duct cells are relatively devoid of invaginations or evaginations, and have a few scattered mitochondria and other intracellular organelles. So let's start with the proximal convoluted tubule first. They're essentially cuboidal, as you saw in the picture on the other slide.

They've got a very prominent brush border. They have, not as easily seen in the previous diagram, but they have lots of... lateral plasma membrane interdigitations. They've also got quite a few basal enfoldings in the mitochondria.

And we have lots and lots of ion channels and pumps, especially the sodium-potassium pump along the basal portion. And the main functions of proximal convoluted tubule are actually pretty significant. It's a primary place for ion reabsorption, some water reabsorption. It's where we take in amino acids, sugars, and certain proteins.

And when you look in a lab under a microscope with a fairly high view, what you'll see is this. You'll see a cross-section of the proximal convolute tubule. And this lighter staining portion here of these cuboidal cells is the brush border. So lots and lots of microvilli.

You'll notice right beside it the distal convoluted tubule and what you don't see is a significant brush border. Turning back to the proximal convoluted tubule, here are some of those basal infoldings I told you about and they seem a little darker because they've got lots and lots of mitochondria in them. And here's an EM view, which again shows you some of the same thing.

Here is the basal border with a capillary right next to it, and you see quite a few infoldings with mitochondria. So time for a little histophysiology. I mentioned that's a place where ions are reabsorbed, and those are glucose molecules, amino acids, and other large molecules like peptides. So to do that, of course, we have to have very distinct apical and basolateral domains.

And we do that by means of tight junctions. We've got antiporters such as proton sodium. antiporters which allow sodium to cross in and leave by means of sodium channels in the lateral membrane and recall I talked about the sodium potassium pump kicks 3 sodium out 2 potassium in and that generates a low sodium gradient which is what essentially powers the sodium movement through these cells as well we've got various glucose transporters and we We talked about the glute transporters before when we were discussing glucose movement. And so we've got several different types of glucose transporters which allow glucose to enter apically and glucose permeases which allow glucose to leave basally. And so it's perhaps not surprising that you would see lots of mitochondria, lots of membrane elaborations.

As well peptides get transported by. by transcytosis across and as they are being transported some of them get broken down by lysozymes which you find. So at the end of the day where all these materials go once they come from the lumen and leave the basal surface, well they are picked up by a very intricate capillary network which surrounds the lumen. proximal and distal convoluted tubules. The loop of Henle is a thin portion, mainly thin, but has also thick limbs which are similar to the proximal and distal convoluted tubules.

While the thin limb, which and juxtamedullary nephrons is really the most extensive part of the lupine family, we see the epithelium being comprised of a simple squamous epithelium. And the descending limb... that is the one that comes from the proximal convoluted tubule and to the medulla, is decidedly more permeable to water. And this allows what's known as the countercurrent exchange system to work. The ascending limb, by comparison, is relatively less permeable to water, but has got lots of sodium and chloride and potassium transporters.

If we look at an EM view, you can see here the thin limb of a loop of Henle in sort of an oblique section as it's leaving a portion of the proximal tubule of the nephron. Light micrograph view, you can pick out some of the distal convoluted tubules and collecting ducts, but also the thin limbs of the loop of Henle, which you can see right here. So here's a thin limb, a squim.

epithelium here you can see various capillaries scattered around but of course there's less cytoplasm they stain less densely so see if you can spot those squamous epithelial cells which form the walls the loop of Henle. And as I mentioned, there's an intricate vascular network, and you can see this really well here. Right next to this thin wall of loop of Henle, you can see a capillary. And the capillary and the loop of Henle actually share some of the same basal lamina. Okay, so I mentioned something called the vasorecta a little earlier, and the vasorecta is really part of the peritubular capillary network which surrounds and supplies the capillary network.

the nephron and there's a branch which goes follows along with the loop of Henle and then one which leaves and ascends as well as not pictured in the slide there are several sort of connecting loops between the descending and ascending part of the vasorecta. The vasorecta is really involved in picking up a lot of the materials which are reabsorbed from the kidney. You can see some of the vasorecta here in this diagram.

Now I don't expect to be able to see it really easily in your particular histological preps. So if you look at thin and thick limbs of the lupus henlii, they're fairly obviously different. Here you see a descending thin limb, squamous epithelial cells.

an ascending thick limb of the loop of Henle, more cuboidal, lots of mitochondria, because they are ion pumpers, as I mentioned, and then these spaces here, which are part of the vasorecta, very closely applied to the loop of Henle. I mentioned a countercurrent multiplier, and the way it works is essentially this. So, I mentioned that the descending limb of the loop appendix is pretty water permeable. And the ascending limb is really specialized for ion pumping. So essentially what happens is this.

Ions are pumped out of the ascending limb. That makes a very salty and... environment in the interstitium surrounding the loop of Henle, that will osmotically attract water, and that water gets picked up and transported away, water and ions get picked up and transported away continuously by the vasorecta.

So, essentially what happens is, filtrate starts off being about equally osmolar with blood, around 300 milliosmolar, and it gets... more and more concentrated as water leaves. So it's around 1,200...

milliosmolar at the bottom of the loop of Henle, and then because we're pumping ions out, it gets progressively more and more hypoosmotic. So essentially we go from being iso to hyper to... hypoosmotic as we course through. Eventually when we get to the top of the proximal convolutubule it gets more eukaryoteosmolar. This whole process kind of reverses as we go out to collecting duct which you can see here.

Because we've got a very salty interstitium here, it's going to draw water out. So a lot of water moves out of the collecting duct by means of water channels. And that gets picked up again by the vasorecta and returned to the blood. vascular supply. So the distal convoluted tubule is again cuboidal epithelium.

It has fewer short microvilli, but compared to proximal convoluted tubule, it has an extensive basal plasma membrane with lots of mitochondria, lots of potassium pumps, and other ion transporters. And essentially, they will drain into collecting ducts. And in this particular image, you can see a proximal and distal conflux of tubules again.

And this isn't perhaps as good, but this would be one of the previous ones I showed you. But here you can see a distal conflux of tubule, proximal next to it. And not as easily seen, but you can see there's more material here, it's slightly lighter stained, than the rest of the cell would be the brush border of a proximal convoluted tubule. And you'll see blood vessels and whatnot and thin limbs of loops of henle mixed in.

So to compare proximal and distal convoluted tubule epithelial cells, this is a great diagram. It shows you essentially the main difference, two main, three main differences. Proximal convoluted tubule cells are a little taller. have taller microvilli and the basal surface is not quite as convoluted whereas it's more convoluted in the distal convoluted tubule shorter cells shorter sparser microvilli So, time for a little histophysiology of the distal convoluted tubule. And, again, there is some reabsorption that occurs here.

Sodium and chloride, amongst other things, get reabsorbed. This is under the control of a couple of... of hormones, but the main one to note is aldosterone, and aldosterone is a product of the adrenal glands, the adrenal cortex in particular, and it upregulates sodium channels as well as upregulates sodium-potassium pumps. So that allows some of the fine-tuning of sodium chloride transport.

Now, I mentioned the juxtaculomereular apparatus, which consists of juxtaculomereular cells and the macula densa. It's at the vascular end of the renal corpuscle. Starting with the juxtaculomary cells, these are really modified afferent smooth muscle cells which have got renin in them. So you'll see some renin granules. As I mentioned earlier, the macula densa are really modified distal convoluted tubules.

cells that are sensitive to tubular chloride and sodium. Essentially you have to think of the distal convoluted tubule cells as being twisted around to be close to the juxtaglomerular cells. And this shows you a juxtaglomerular cell of the afro-arterial.

And there are lots of granules in here which contain renin. And we'll talk about renin very briefly. Essentially. low blood pressure in the afferent arteriole causes renin to be released that reacts with angiotensinogen to make angiotensin 1 and that's converted by angiotensin converting enzymes into angiotensin Angiotensin II has got a couple of rules, yet amongst other things acts as a vasoconstrictor.

So that means it raises blood pressure, but it also upregulates aldosterone from the adrenal cortex. And aldosterone causes the kidney to retain water and sodium mainly by upregulating sodium transport molecules. If you increase sodium reabsorption, you increase the amount of sodium in the blood water is going to follow.

As well, I mentioned one of the endocrine functions of the kidney, that is the release of erythropoietin. That's really primarily juxtacomero cells, which release EPO, or erythropoietin, and that stimulates bone marrow cells to make red blood cells. You may have heard of athletes doping.

They can dope in a couple of different ways, of course, but endurance athletes, such as cyclists, have been caught using erythropoietin, which the kidneys normally make, and that is used to stimulate their bone marrow to produce more red blood cells. And of course, with more red blood cells, you've got higher oxygen carrying capacity. Now, let's look at the structure of the juxtaculomary cells, or the positioning of the juxtaculomary cells relative to the macula densa. So again, juxtaculomary cells are modified smooth muscle cells of the afferent arteriole. So here's the afferent.

arteriole here and clustered in this area is our juxtaglomerular cells these mesangial cells which are essentially phagocytes and are contractile and the mesangial cells are the mesangial cells. macula densa and together the macula densa which is sensitive to chloride but also to sodium and the dexamera cells which are sensitive to blood pressure together collaborate in the release of renin and this shows you in a bit more detail what I was just talking about so the Cells of the distal convolutubule, which comprise the macula densa or dense body, sense changes in sodium and chloride. And cells of the juxtaglomerular apparatus sense changes in blood pressure. Together, they collaborate in renin release. Renin and plasma converts angiotensinogen into angiotensin I.

And then, enzymes called angiotensin-converting enzymes, change it to angiotensin II, which in turn is a potent vasoconstrictor, but also upper-regulates aldosterone from the adrenal cortex. And aldosterone functions mainly at the distal convoluted tubule, and together, the enhanced sodium uptake and vasoconstriction increase blood pressure. Now, understanding this is not just a moot point. It's kind of cool because...

This led to the development of several very useful tools in the toolbox that's used for treating hypertension. So for example, there are a couple of classes of enzymes such as the angiotensin converting enzyme inhibitors or ACE inhibitors, which block the transformation of angio-1 into angio-2. And so we...

So we use drugs such as Valsartan or Candasartan, and these are, I'm sorry, I beg your pardon, I got a little ahead of myself. We use drugs like Captopril, which is an angiotensin converting enzyme inhibitor to prevent angiotensin 2 from being formed. So anytime you hear a pril at the end of a drug name, it's probably an ACE inhibitor.

And as well, Because we know that angiotensin 2 is a potent vasoconstrictor, we've also got angiotensin receptor blockers, or ARBs. And examples of ARBs are drugs like Valsartan and Candasartan. So PRILs are ACE inhibitors, so Captopril would block this step here.

Whereas angiotensin receptor blockers, or ARBs, such as Valsartan, Sartan and Cantosartan will block this here. Alright, and just to prove to you I'm not making all this up, here would be of course the renal corpuscle with the bone in space, glomerulus here, and afro-arterial would be someplace in this vicinity, but here this little row of cells is the macula densa. So look closely at your lab specimens and you should be able to find some of these.

And this shows you a diagram of what I was just talking about. Afrin arteriole, effrin arteriole, afrin's larger than effrin, it's going to boost blood pressure and the glomerulus enhance filtration. as well as juxtaglomerular cells, macula densa, and mesangial cells.

So together, the juxtaglomerular cells and macula densa sense changes in pressure and osmolarity and cause renin to be released. On our trip through the kidney, of course, we're going to end up eventually in the collecting tubules. And these essentially function to transport filtrate. to papillae and medulla and cortical and medullary collecting tubules both end up at these papilla and they have a couple specialized cell types, principal cells and intercalated cells.

The principal cells have relatively few mitochondria, just a few short microvilli with a few basal plasma enfoldings. So we're not really sure what the functions are. The intercalated cells have got a plasma membrane with microplicae, lots of apical vesicles, a bunch of abundant mitochondria, and they're more involved in hydrogen ion secretion. Collectively, though, the cells of the collecting tubules can be manipulated to enhance water movement.

And this is done by means of a hormone called vasopressin, or antidiuretic hormone. And what ADH does is cause the insertion of water channels called aquaporins, and you can read about that in your text. into the plasma membrane and this makes it easier for water to follow sodium out of the tubules and into the interstitial area of the nephron and from thence into the vasorecta And this shows you some of the cells of the collecting tubular, and you see intercalated cells and principal cells. And so we think that intercalated cells secrete either protein or protein. Protons are bicarb and may be involved in potassium reabsorption.

The principal cells are also thought to be involved in sodium transport and water and secreting. potassium, although we're not totally sure about which does what. The aldosterone that I mentioned coming from the adrenal cortex is what stimulates the reabsorption of sodium here, but it's mainly vasopressin or ADH which is involved in water transport. We're getting close to the end here.

The urinary tract really begins with the renal calyces and renal pelvis. So once urine filtrate is finished off and formed, and we're dealing with a hyperosmolar filtrate, usually around 12. 1200 to 1400 milliosmoles compared to about 300 milliosmolar in blood. And this drains from the calyces into the pelvis and then out of the ureter and into the bladder.

The last few things I'd like to do is compare the layers of the ureter and bladder and their epithelial lining. We'll pay special attention to the transitional epithelium, which you've identified before in the lab exam, but we're going to talk a bit more about some of its finer structure. So here are pelvic calyces, which eventually... empty into the ureter.

And the ureter, like the kidney, also has a transitional epithelium. It's quite highly enfolded, but can stretch. So there's a mucosal layer here, from here to here.

There's a muscularis and a cirrhosa or aphantasia around the whole thing. And it can increase in diameter to facilitate flow. Right underneath this transitional epithelium is the lamina propria. So together... together the transitional epithelium and the lamina propria, which is a vascular connective tissue area, make the mucosa.

And you can convince yourself this is a transitional epithelium again by looking at the nuclei of the cells in the unstretched ureter. And you can see that they're nice and large and rounded, just as they would be here, towards the bottom. And this helps you distinguish it from, say, a stratified squamous epithelium, because these cells...

the luminal side or anything but squamous. And you all know that the bladder has a transitional epithelium, which allows stretching. And so these big folds of transitional epithelium in the unstretched bladder come with this connective tissue of the lamina propria. And when they...

the bladder is filled with urine, of course, that all stretches. Now, there's a few more details about the transitional epithelium which are worth knowing. There is a very unique specialization of the transitional epithelium in the bladder, which include these little plaques.

And these apical plaques are really basically aggregates of intramembrane proteins, and they're anchored to cytoskeletal proteins on these cells, so that when the bladder stretches, the transitional epithelium, of course, stretches, and... the luminal cells flatten out, but there are plaques, these plaques here, which help anchor the apical regions of the cells together. So it's a very fibroelastic conglomeration of cytoskeletal proteins, which allows stretching.

And with that, that ends our trip through renal structures. If you have any questions, please let me know.

Transcript for:Comprehensive Overview of the Renal System_BILL_DJ_KIDNEY_LECTURE

Transcript for:
Comprehensive Overview of the Renal System_BILL_DJ_KIDNEY_LECTURE