let's get into the urinary system the urinary system has many components to it classically everyone thinks of the kidneys the uriters the bladder and the urethra but I want you to pay attention to see if there's anything else that you can add as a component to it we've got two major filters that are going on in our body we've got the liver and then the kidney the kidney is great at changing the fluid level within the body quite easily right the blood is hooked up to it the fluid goes through there it starts to separate things into their components things that are cellular sized are maintained things that are smaller than proteins end up getting filtered through here so this is going to be the way we regulate our total volume if we have a concentrated um urine we're trying to hold on then to more water in our blood system if we've got a dilute urine a clear ur urine we are then going to be trying to uh offput some water we also have our way of controlling ions through there and we help to control the extracellular fluid ions through the kidney as well we can end up retaining sodium or getting rid of it and remember we say water runs towards the salt so if we have a high salt concentration in our body where our extracellular fluid is going to be uh larger constantly we have this carbon dioxide that comes into our body the CO2 and CO2 inside the body as an acid we are going to be using the kidneys and helping to buffer uh and get rid of some of that CO2 and carbonic acid that we have we got tons of metabolic wastes that we're going to go through there and after we've taken some toxins detoxified them some we're going to get rid of them through uh the kidney as well you take in drugs and we say that drugs have half- lives both your liver and your kidney are important for getting things down to their halflife and eventually excreting it in fact some drugs can be detected in your system even when they're no longer active because we have not filtered all of them through the kidney our kidneys are great at regulating our amount of red blood cells in fact if you have bad kidneys if you will we lack this thing called ureiththropoetin which helps us to regulate our red blood cell level our kidneys do an amazing job of activating vitamin D your skin can make vitamin D you can orally intake vitamin D and your kidneys can activate it right we can carry out gluconneogenesis if it's needed with the kidneys and so the kidneys again part of this urinary system and together we can think that with the other organs there we've got the urers connecting directly to the medulla of the kidneys the uriters then go to the urinary bladder and eventually to the urethra there that transports it outside the body here we've got a beautiful image of it this is the kidney here this is the other kidney right here the patient's left kidney we're looking at at that renal vein going across the aorta there on top of the kidney we have the adrenal glands the supra renal glands if you will the kidney has the renal arteries and the renal veins going to them when you hear the term renal I want you to say to yourself does it involve the kidney this is that urer that's making its way down and it's going to into the back of the bladder this is a female so when we look at the urethra it's going to be a short urethra we're going to talk more about that when we talk about infections that might happen with it as we look at it again here we can see that sup that superior misenteric artery going directly over that renal vein right i just want you to be able to get a hold of where we are at in the body what we're not showing you in this picture is that the liver is right here the liver uh is actually quite large and the thing that I don't like about this picture or this picture is that we don't give you a true representation on how much lower the right kidney is than the left when we do a CT and MR you can still end up seeing them in the same plane however the right right kidney is significantly lower now what's on the opposite side over here we're going to end up having the spleen that's right in here so they're going to be in intimate contact with each other again what this picture doesn't actually do a good job showing you is that the kidneys along with the aorta uh and the other great vessel here they are actually retroparitinal we'll get into that deeper later but they're stuck against the back wall they are suspended when you and I are in our standing up positions they're not just falling down in into the pelvis because they're retroparitinal they're stuck against that back wall we can see all the different functions that we have here that we regulate with the kidney we're going to explore those as we continue on throughout this lecture remember whenever we see lists we see multiplechoice questions so when we talk about the functions of it we've got these multiplechoice questions that can come out when we talk about the organs of the uh renal system right we can think of these guys but I want you to keep paying attention to see if one more fits into that category this is a nice little recap of what we just talked about here now we're looking at this in the presence of a cross-sectional image here here we have a CT and one of the words we see here is pilitis itis means an inflammation or an infection here and pilitis means we're gonna have like a pus so we got an infection of the renal pelvis and the kalousy here let me first show you what a normal kidney should look like this is normal here we have got some u abnormality infection here in the pelvis of this kidney we also see it here a little bit now we've got some pyonfritis coming on right in here will have something called nefrons which you'll learn about in a little bit we got an infection or inflammation of the entire kidney we talk about pyonfritis right infections in females are usually caused uh by feal bacteria entering the urinary tract via uh via the urethra gentlemen who are watching this lecture one thing that we as as men are never taught is how to wipe from the front to the back when we are when we've gone uh and taken a bow and had a bowel movement young ladies are taught from the very beginning to wipe from front to back so they keep any ecoli that are in our feces from getting into the short urethra the the shorter urethra of the female allows a bacterial infection to easily climb up the urethra make its way into the bladder which generally causes a bladder infection but if a bladder infection is bad enough it will climb the urer and even get into the kidney antibiotics have significantly decreased things like pilitis but they still happen when we think of urinary tract infections in males we normally think of them being in u in young males infants not that they can happen in men they still happen but the the comparison uh there is none women have them at a much higher rate so the blood comes from the heart right through the abdominal aorta through the renal arteries which are just inferior to that superior misenteric artery i want you to keep remembering where things come off of the aorta right know where the celiac artery is followed by the superior misenteric right followed by the inferior misenteric know where you're coming off right there just off laterally from the superior misenteric or where we have the renal arteries coming off we've got two of them going through here and if we were to go through all this let me go back for a second here as we talk about that superior mucentic we're less than an inch below it when we have that renal artery coming off we're much higher up than we are with the uh inferior misenteric here we're showing the blood flow through the uh kidney again but one of the things that's really really impressive is that the renal arteries are delivering 1/4 or basically over a liter of blood right over a liter of cardiac output of the blood each minute this is a significant amount so we are really recycling and cleans cleansing the blood throughout every minute and imagine how many pints of blood do you have right that's what you have to say to yourself in order to understand how quickly we are filtering the entire body if you think about it we have about five lers of blood in us so in less than uh you know 5 minutes let's say 4 minutes you have recycled all the blood in your entire body now as we increase our physical activity that goes even faster so the arterial flow this is what I want you to remember on how things go through and I want you to be able to pick out which ones go with which the venus flow is basically the arterial flow but backwards okay so the nerve supply is via the sympathetic fibers from the renal pelvis remember all the sympathetics come off uh T1 to L2 here we have some of those that have crossed the diaphragm there and they are then supplying the renal pelvis and when we have that we can constrict right these vessels there are no parasympathetics that ride on vessels so when we talk about the sympathetics to the pelvis I want you to think of some of them and I should say sympathetics to the kidney some of them will be internal but the major ones I want you to think coming right in here to this renal artery trust me we will have further input that constricts these vessels as we're going through right now i'm just discussing the renal artery then again this is how we're going to be going all the way through the system and you want to know this entire pathway right here remember the aorta off the aorta just below the uh superior misenteric on the lateral sides we're going to have that renal artery once we get inside the kidney that renal artery is going to lead to the segmental arteries those segmental arteries are going to be coming around and they are going to be coming up and they're going to be interlobar arteries interlobar arteries are going between the pill so these are interlobar arteries ones that arch over the pill we call those arcuate arteries and these ones shoot out like rays so these are cortical radiate arteries in that cortex right there and once we're in there going to the various glomemeuli we're going to have the aerant uh arteries coming in then the aerant coming out we'll have some perubular capillaries which I'll show you in some images here and we're going to work our way all the way back to the inferior vennea going into uh the right atrium after that we can then look at that coming all the way through and again use this as practice as you're going through now here we are this is the glomemeilus this tuft of blood vessels coming in right here's the aerant arterial coming in the eerant arterial so the apherent arterial comes in and it leads off and gives us these glomeular capillaries once we've gone through that as the blood comes back through it's going through an epherent arterial interestingly enough when we think about the blood vessels here normally when we think about uh capillaries we think of an artery an arterial going through capillaries then going to a vein here we've got an arterial eventually going to another arterial here that's the glomemeilus now outside of that we've got this guy called Bowman's space Bowman's capsule right in here all right and with that when we combine Bowman's capsule with the glomemeilus together we're going to call that the renal corpusle the renal corpusle off the backside of that we're going to have the proximal convoluted tubule and I'll show you the tubules so we get the concept of what a nephron is a nephron is the renal core pusles and all their tubules so virtually this is the nefron right in here we'll get there as we're looking at it here these particular capillaries uh we have different styles of capillaries right these are the fenistrated capillaries they've got small holes in them the holes are small enough that we don't leak cells through them right but we and we don't even leak large proteins what we do leak is glucose we leak amino acids through there right if we disrupt those fenestrations we can end up getting blood into the kidneys but that's not really happening right we we're getting through uh amino acids sugars and various amounts of waste that are going through so they're coming through right in here and they're coming out and I'll explain to you of how these uh pto sites and how they are going to end up affecting it remember podiatry pto sites are going to have lots of foot processes we're going to go through that the uh glomemeular space here that's also Bowman's capsule that they're talking about with it we've got two layers right now the organ itself remember organs have a visceral layer the outside is a parietal this is the visceral layer of it right here the visceral layer of the renal corpusle right and this is the pridal layer of the renal corpusle or we could say the visceral layer of Bowman's uh capsule right and the parietal layer of it right in there and I want you to think of as the fluid comes through out in here in this Bowman's space that we see that's where we're going to have pre-urine when I say pre-urine as it's going to have the constituents of urine but it's going to have a lot more than that it's going to have things that we want to steal back and get into our system such as glucose and amino acids and and a few other things here when we're talking about it here we're showing those ptoytes and the protoytes have those little foot processes that are coming on there and they're clinging to the glomemeuli here there's the protocyes foot processes there and they're coming through and you're noticing they're right by the filtration slits they help determine what's going to be filtering out okay we're looking at it all over again and right as we come here we've got something called the proximal convoluted tubule the proximal convolute tubule we wouldn't say proximal if there wasn't a distal this is the distal convoluted tubule what's between the proximal and the distal is going to be this guy called the loop of henley the loop of henley there's going to be a thin limb and a thick limb you and I are going to focus on the thin limb as far as looking at things hisytologically and there are various functions that go on with the loop of henley and I want you to think about concentrating urine when you think of the loop of henley we're going to notice that a lot of our valuable things are reclaimed here in the proximal convolute tubule we'll get into that in a minute the distal convoluted tubule a lot of things actually get secreted back into the tube uh that's going on through there uh we do reclaim some things but eventually we're going to get into this guy that we call the collecting duct the collecting duct when we have things that enter here I want you to think of it as being urine the only thing that gets modified here is sometimes that urine gets some of the water continually reabsorbed through there we're going to have things called aquaporin channels we're going to have some here in the collecting duct we're going to have some uh here in the um proximal convoluted tubule looking at it all over again here we can see that parietal layer of Bowman's capsule bowman's capsule is also called the comular capsule in today's times I call it both ways likely on your test I'll be calling it Bowman's capsule because I'm an old man and I like to keep old when you leave me you're going to be running into other old people and they're going to call it Bowman's capsule as well but notice at that parietal layer it's simple squamas cells this is that parietal layer nice and simple squamas cells they do have tight junctions right in there so they're holding things together now we also have with it the visceral layer this is the visceral layer of that uh Bowman's uh capsule there and we can see that they've got those pto sites this is the pto site and look how many feet that pto site has and so the fenistrated capillaries are down in here and they're going to be overlapping with the little holes that they have in it with those fenestrations that they have pointing to it there so off of all of that we're going to have a renal tubule the renal tubule is quite long it's got three major parts the proximal proximal convoluted tubule the nephron loop which we pointed to a little bit ago and that distal convoluted tubule each one of them has a slightly unique function to them there is some overlap between them as well and after these guys we've got that collecting duct that has the urine in it that can get aquaporin channels when we are severely dehydrated here beautiful we're looking at it all over again when we are looking in the cortex of that kidney we're going to see them looking like this they're even more highly convoluted than what this is but that proximal convoluted tubule that's this guy coming off of it that's what's reclaiming the vast majority of those valuable things like our glucose and our amino acids now there is no free lunch we have to spend money if we want to reclaim things and that money is going to be the form in the form of ATP adenosine triphosphate and so in order to get ATP we have a major organel that allows us to do so that's going to be the mitochondria that manufactures and makes that so that means we have a lot of mitochondria inside these cells and there's more there in the proximal convoluted tubule than anywhere else within the system that's not to say the distal doesn't have have them at all they definitely do but not nearly to the same degree that the proximal does that's going to give the proximal convoluted tubule a unique hisystological loop if you're looking at an H& stain one of the things that I want you to look for is that the proximal convoluted tubule stains a little bit more hot pink in comparison to the distal convolute tubule inside of it it'll also look like it's got sort of a fuzzy brush border going on inside of that and that's because there's going to be a ton of microvilli that are there to increase that reabsorptive area all right here we're looking at it look at all those microvilli look at all that mitochondria that's there we've got all that ATP being made we are pulling back that expensive glucose we're pulling back those proteins i want you to think about a condition called diabetes diabetes was first uh talked about when people could almost taste a sugar to the urine all right and what that meant was not that the kidneys weren't absorbing the sugar that got in there but it meant that there was so much sugar getting sent to the kidneys that it overwhelmed the ability of the apical membrane with its microvilli to pull back all of that expensive sugar we'll talk a little bit more about that later let's move on uh to the nephron loop there's that nefron loop coming through we're using that to modify the urine we're using it to concentrate the urine now we've got one coming down that must be the descending loop and one going up that must be the ascending loop so here we are we're looking again at this distal convoluted tubial we can see that there's a looks a lot like this we've still got the same cubuidal cells there there are microvilli but there are few microvilli in there these have a lot more mitochondria these still have a decent amount of mitochondria but because they have fewer they stay less intensely pink in an H and E stain still in the cortex of the kidney right now with that said this this doesn't do it justice on how this loops through let's come over here this is that distal convoluted tubule and I want you to see how part of that distal convoluted tubule comes into intimate contact with the glomemeilus we have got both an aerant and eerant blood vessel coming here and its intimate contact is going to allow us to send different signals that are going to let us know whether we need to constrict or dilate these vessels for the aerant aerant and we're going to release various things when we get there see this is that distal convolute tubial that distal convoluted tubule and again we're going to be modifying the aerant and eerant arterial input based off of the information that is released and the signals passed on um at this area right in here here's the eerant arterial they look at the apical membranes there you still see these microvilli you just don't see the same amount you still see mitochondria you just don't see the same amount so an H& stain it's going to look a little pink just not as intensely pink comparing the two we see that all right here we are look at this glomemeulus what are these glamuli when we talk about the aerant eerant arterial coming in these are the capillaries this is where if we look in there histologically we are going to zoom in and we're actually going to see blood inside of this because these are the blood vessels these are capillaries that we see in here here we see the glomemeular capsu and capsule in space here remember I also call that Bowman's capsule in space the the terms are synonymous when you leave me people are going to use the term Bowman's we can see that we've got proximal convoluted tubial i want you to see how this is staining fairly intensely pink right this is also going to be proximal convoluted tubial proximal convolute tubial this is more what a distal convoluted tubule is going to be here's another example of it here still cuboidal cells still pink just not as intensely pink as we see with the other in this picture that we see right in here we are no longer in the cortex of the kidney we're down in the medulla down in one of the pyramids that are there and remember we talked about the the loop of Henley the loop of Henley had that thin loop where the the cells were squamus like so so we could easily allow things to pass back and forth that's what you're seeing right in here it's how we're going to be exchanging and pulling things back so when we're talking about the collecting duct that's when we're talking about more of these cubuidal guys remember those collecting ducts begin in the cortex but then we end up finding them also in the medulla these are the cubuidal cells that make that up all right do they have microvilli very very very few all right again the principal cells that you're going to find in here their job is to maintain sodium balance uh the intercolated cells we're going to have cubuidal cells within that that have um more abundant microvilli and so I want you to know that there are significantly less intercolated cells as there are principal cells in there there are two types of intercolated cells there's both A and B and both help help maintain an acid base level of the blood i want you to think about this way if you have a lot of acids you would denature your proteins your proteins would break up so we've got to get rid of those acids one way that we do it is we breathe off carbon dioxide right we're getting rid of the acid that way another way we do it is through the kidneys so the collecting duct that same guy that we're seeing right here this guy right here that collecting duct collects and receives filtrate from the nephron remember the nephron is both the glomemeulus the capsule the proximal convoluted tubule the loop of Henley and that distal convoluted tubule there so that's going to run through the medulla it's going to give uh it's going to give part of its thing through the pyramids in fact it's going to make up a good chunk of the pyramids and it's going to be stripes uh like appearance there the ducts of them all together coalesce and they fuse together to deliver urine through the pill into the minor kalousy so they come together and urine just drips off them from the minor into the minor kalcy so here we see them again i want you to think of these guys several of them coming together eventually bringing their fluid and dripping into a minor ka perfect think of several of them coming together there as we come over here we got the medularary pyramids and guess what these pyramids all are which are in the cortex are all going to try to reach this pelvis but they've got to come here they've got to drip their urine here drip that urine into a minor kalousy which is going to then go into a major and then the pelvis here this doesn't show a great uh major kacy but the concept is still the same and then the urine's going to go through there all right looking at that whole thing again now you have the ability to compare all the cells together there so classes of nefron when you look at the cortex we've got ones that are right at the cortex medularary border there they're right next to it but they're still in it so they're juxtaposed or they're juxta medularary ja means next to these are the ja medularary nephrons outside of that we've got the cortical nephrons both in the cortex but this is the cortical nephron here these make up 85% of all the nephrons okay these just glam their nephrons they've got that long loop of henley there look how long that loop is so what are they doing they're helping us concentrate that urine even more beautifully here we're looking at the capillary here but look what we've got right here they're going with the loop of Henley we've got vas recta through the vasorrecta system with this loop of henley that's how we're going to be modifying the concentration and the fluid with inside that loop of Henley now these renal tubules also have a blood supply to them because we're going to be constantly modifying the things that are that are there remember we've got an aerant u I should say an aerant duct and eerant duct right so a proximal convoluted tubule a distal convoluted tubule well we've got to get things in and out so we're going to have to have capillaries that sort of run in that area and we call those perittubular capillaries perfect this is just what we would look at this is an electron microraph of the entire thing here that then someone has added color to it here beautiful glomemeilus going on right there and we can see the supply of the aerant arterial coming in right here and then the eerant arterial leaving one thing that some handwritten drawings don't show us as well is that the aerant arterial is usually a little larger than the eeren arterial by doing so it helps us change how filtration works we'll see that as we continue to go on love this picture and the reason why I love it is because it shows you what we're getting getting back in different areas right in here sodium remember it's so expensive that the Romans used it as a form of currency glucose is also expensive so we're pulling that back along with the amino acids well guess what you see the little zigzag in there zigzag zigzag that's going to tell you that we're doing with that with active transport active transport requires money it requires adenosine triphosphate ATP so we're going to be spending a lot of ATP in here so we're going to have to have a lot of mitochondria that's not saying that we're not doing any over here right in that distal convolut tubule we're just going to be doing a lot more of it in here you're also noting that we're not really getting back amino acids and glucose over in this region that's not the function of the distal convoluted tubule that loop of Henley and look we are pulling back salt and the the the old saying is water follows the salt so sure enough we're going to be doing that as we come over here into this collecting duck we've got that pre-ur now we're still getting or I should say it's really becoming urine at this point we're still getting things out of it you see where it says water right here when we're under really good dehydration we concentrate that urine remember your urine gets darker and smellier well we insert aquaporin channels here there are aquaporin channels in the proximal convolute tubial but we insert a lot more of them under various conditions when we release things um like ADH when we release things like um angotensin 2 we'll talk more about that as we go but you're also seeing that we're modifying it and we're pulling back some ura which is very interesting because guess what we want to get rid of ura ura is a toxin it'll come out here much of it will come back in and go through the system and they loop back and forth it's just an interesting concept and I have no idea why we do it here atp perfect looking at this thing you might be wondering why do I keep showing this guy this beautiful guy is the basis for truly understanding much of the function of the kidney i want to go through this all over one more time here right we call this whole structure the renal core pusle the renal core pusle has the glomemeular capillaries in it it's got the Bowman's space right also called a glomemeular space right the Bowman's capsule this is that uh visceral layer of it this is that parietal layer of it in this area we've got these meangio cells the aerant arterial making its way in the eerant arterial making its way out that's that renal corpusle right off of the renal corpusle we've got that proximal convoluted tubule where we have tons of mitochondria and we've got these microvilli going crazy all the way through there remember we have the proximal convoluted tubule that loop of Henley coming through and then the distal convoluted tubule is going to loop back through the distal convoluted tubule is going to have these unique cells right here we're going to call these the macula denza they are sensing the salt concentration that we have and then a signal is going to go through the granular cells and it's going to affect what's going on in that aerant arterial these granular cells are really going to affect that apherant arterial and we'll talk a lot more about that as we go on many of the drugs we're going to give you uh when we go to affect blood pressure are going to work on the eerant arterial internal body aerent arterial drugs that we give you eerant arterial enough about that i also want you to know that we have this these three things this complex these extra glamarular uh misangial cells going with the granular cells and the macula dense of the distal convolute tubule and that's called the ja uh glomemeular apparatus remember jxa means next to you to so it's next to the glarulus perfect now we said that we had some extra glamular meangial cells that must mean we have intra glomemeular messangio and that's what we'll see in here i'll touch on what that means later looking at it just talked about all of this i broke it down for you on that big picture pause this video when you get time and you can look through that all uh together love those granular cells in here now let's talk about those granular cells for me those granular cells are awesome they're all in a bag of chips why because they release something called rein or renin I could care le however you say it and that rein is going to work through a ras pathway which I'll go into deep detail with but this rein or renin that's going to get released is going to go through it's going to end up cleaving something that's called angotensinogen into angotensin one there's going to be this huge complex that goes through the ras pathway that helps us control blood pressure much more on That again remember this is that distal convolute tubule with that macula densa sensing with that sensing the sodium load helping to control what happens in the jugglomeular cells i've said it several times so it must be very important to me and it is the extra glomearular meangio cells that we have in here look at those guys right they are located between the arterial and the tubular cells interconnected with the gap junctions that are there we have gap junctions within this guy and they may we don't know they may pass signals between the maculadensa and the uh granular cells we just really don't know what they do beautiful complex all over again moving on so the physiology of the kidney what's it doing well guess what it is processing the urine right 180 L of urine is pro are processed daily all right but with that said 180 L we're only making 1.5 L of urine through that so the kidneys are filtering the entire plasma 60 times each day but they're not making that much urine that's how great we are at both filtering and bringing back things and even bypassing it many things that go through that proximal convoluted tubule right they get reabsorbed but wait a second let's go back to this apherant arterial guess what through the peritubular capillaries that are in here right and through uh the glomemeular capillaries things are getting right back in out through that uh eerant arterial here's the aerant coming in the aerant going out perfect so and it says consumes 20 to 25% of oxygen used by the body at rest man so if I do a thermal scan of you right there must be a lot of blood going to you cuz that's how I deliver oxygen and sure enough just like the head where we have tons of ATP tons of oxygen/ blood going if we do a thermos scan the kidneys are going to have much of the same thing i love this picture because it shows us here at the glomeular capillary things coming into the proximal convoluted tubule and remember I told you we want to pull back uh a lot of things from there and we're going to be pulling back the sugar we're going to pull back that those amino acids and a few other things directly into those perittubular capillaries we're also going to have some tubular secretion in there because we've got waste that we're trying to get rid of and remember how my colleagues and I make questions we we do multiple choice right can you see A B and C make sure you read through and understand them like tubular reabsorption selectively returns 99% of substances from the filtrate uh to the blood wow all right so the glomeular filtration that's this guy right here passive process when they say passive that means there's no energy being used right no ATP expenditure and glamaria the filtration it's going to be based off of a pressure system we're going to have a higher pressure load coming in I should say coming in this way and we're going to be lowering the amount of fluid because of that pressure system i have some slides later that really go into that uh and it explains how things are pushed in versus how we try to hold on to things however I want you to know the net pressure although not high is into the glomemeular capsule this Bowman's capsule on its way into that proximal convoluted tubule so we talked about those um capillaries having fenestrations right fenestrations large enough to allow amino acids through large enough to allow glucose through not large enough to really allow uh proteins through if somebody said peptides make it through there remember peptides are short uh proteins maybe some smaller ones are going to get through there we can see looking over here at those guys but look we also talk about the basement membrane there of it see that purple basement membrane the colors are colorcoded here so it's a fused basil lamina to two other layers there the two other layers I want you to think of look there's the ptoytes look there's the fenistrated endothelium i have some pictures later that go through that for us there are those photo sites coming through there take your time and look through this pause the video as you need to beautiful fenestrations beautiful foot processes there look through it again now we are going through and we're looking here are the glomemeular capillaries right we can see that the blood pressure ultimately is going to be a little higher than the pressure is in here so we're going to get a net filtration coming out and these are the fenestrations that we talk about right we have that fenestrations then we have this basement membrane and then we got the foot processes of the pto sites so we are being very selective on what can make it through so we've got macroolelecules let's go back over here and look at this for a second you might have macro remember macro means big right so we have might have big molecules that can get stuck in this area that we can then modify and get them out there so macroolelecules stuck in the filtration membrane are engulfed by glomeular misangial cells they're engulfed removed right and when they say glomemeular misandria cells they mean these guys right in here these meandriio cells are called intra glomemeular misangial cells they're engulfing it again modifying what goes through there and then those guys recycle it back into our system there ah and here we're talking about the uh things that do this we say water of course we're bringing water back there sugar amino acids and it says nitrogenous waste i want to make sure that I say this most nitrogenous waste gets to and stays within the urine why because we don't want ammonia in our body the nitrogenous waste means ammonia if you've ever smelled ammonia it's a very strong scent if you smell uh cat's pee it's a very strong scent there's a much greater concentration of ammonia in there we have ammona ammonia coming through our system that's a part of those nitrogenous waste that we're then going on the plasma proteins are coming through here but they're too big to go through those fenestrations so they'll stay in the capillaries and then they'll come all the way back to that eerant uh arterial they help provide a osmotic pressure we call it a colloid osmotic pressure to hold on to the fluid that's there and when I say hold on to it remember there's still a net filtration going out but we don't get rid of all of it we still hold on to quite a bit of it as it's coming through this is maybe an even better pe picture of it here we've got this blood pressure coming through this the glomemeular pressure coming in and it's a high pressure right this high pressure coming in that pressure is trying to force its way out but we've got other pressures uh keeping things in the proteins in here the enotic pressure which most of that's going to be done through a protein called albumin i want to say that again albumin is holding uh some of the fluid in that's acting as a force that's holding it in as well as there's a certain level of pressure that's in this glomemeular bowman's capsule that's also pushing things back in but ultimately the glomemeular um blood pressure is high enough that it overcomes it overall we can look at the different pressures we've got 55 uh coming pushing out 30 and 15 pushing in so we've got a net 10 mm of mercury pressure towards filtration there aerin arterial and eeren arterial you see the size of that eerin arterial that the size of this eerant arterial by the way this is the aerant arterial the size of it tells you that hey as things are coming through it's a lot harder for it to continue on right in there again when we give you drugs right when we give you drugs we're going to be affecting the apherent arterial when your body is trying to control the pressure through the kidney it's going to affect the aerant arterial that you see right in there moving on here ACE inhibitors i want you to write down ACE inhibitors i'm going to talk you through ACE inhibitors later and how they affect our blood pressure and they do it via multiple pathways all right so we've got a colloid osmotic uh pressure again that's going to be the albuan that's passing through here that's sort of and actually I almost wish that this was highlighted in a light brown this is the colloid osmotic pressure that's already inside here the albumin already in here holding on to it and we say that that's 30 mm of mercury so I should have changed the color that this is we've got this uh hydrostatic pressure that purple coming out right in there and overall we have got that 10 mm of mercury filtering things out here showing it all over again showing the whole concept all over again but this is when we talk about glomeular filtration rate gfr glomeular filtration rate and we say glar filtration rate we say it's going to be 125 mil millilit per minute and that's just the average right in there right 125 milliliters per minute that's coming through this guy and it's directly proportional to the net filtration pressure the net filtration pressure the pressure going in right in here if we increase the pressure going in we're going to increase the glaro filtration rate okay it's also related to the total surface area available for filtration if we don't have a very big surface area we don't get as much uh filtration out we don't get as much fluid out all right so regulation of glaria filtration what's regulating the filtration through here again we have a constant GFR we said that 125 milliliters uh per minute there right the goal of the intrinsic controls right is to have renal autoregulation in other words the kidney controls what the kidney does right not other areas of not other areas of control it's like the kidney's got its own little brain it really doesn't but it has its own intrinsic control and that's part of the reason why we can donate a kidney and it then functions for the next patient because it autoregulates itself the apherin arterial dilates when the mean arterial pressure falls below 70 mm of mercury why is it dilating it's dilating because it wants more flow coming through it the epherent arterial does not change but the apher arterial gets bigger why so the glomeular pressure maintains a constant state there so the apher arterial constricts when the pressure gets too high and all of a sudden we don't want to rupture these glamular capillary so if I've got a lot of pressure coming in the aeron arterial is going to say what and it's going to squeeze down and by squeezing down it's going to allow less fluid coming in here that then ultimately decreases the amount of glomemeiltration GFR glomeiltration rate okay now some exttrinsic controls uh for glomeial filtration rate that's when we're going to talk about ACE inhibitors right angotensin blockers diuretics many other things that are there that's how we're going to control it when we have problems with our blood pressure we've got those intrinsic controls that we talked about for uh renal autoregulation that's what I just talked about a second ago a little bit that's the ability of the a kidney to maintain a constant GFR it's intrinsic and says it maintains nearly a constant GFR filtration rate when the mean arterial pressure is in the range of 80 to 180 millm of mercury what does that mean look how broad of a range all right of blood pressure that it can maintain its filtration rate at it's pretty awesome so your blood pressure would have to get extremely low in order for you to not be able to autoregulate through your kidney and your um your blood pressure would have to get really high for you to not be able to autoregulate with your kidney the amount of um fluid that's going to go through the glomemeuli so therefore our glary filtration rate is still constant the two uh types of renal autoregulation that we think of are a myiogenic myo means muscle so we're going to have a muscle clamp down in that area and we're going to have tubular gular feedback mechanisms the feedback mechanism is going to say whoa we've got too much pressure so it's going to slow it down so myiogenic again muscle this is that aerant arterial it's sensing the pressure going through it so the smooth muscle contracts when it's stretched if it's being stretched that must mean there's an increased blood pressure and that's going to cause the smooth muscle of the arterial to stretch that's then going to lead us to constriction of the apherin arterial right when we're constricting it it restricts the blood flow getting into the glomemeilus by doing so we are protecting the glomemeulus all right and so where decreased blood pressure causes dilation of that apher arterial right just the opposite when it's a decreased flow there we're going to dilate it and therefore we're keeping it constant exactly what we said before now when we talk about the tubular flow right I want you to imagine that at that distal convoluted tubule we have a flow that has changed right we either have uh a salt concentration that's gotten there and that's then modifying it so that's what we're responding to inside this distal convolute tubule we're going to have a certain concentration of sodium chloride and the macula densa is going to give that signal to the uh ja other cells that are the jxar cells um right these granular cells that are then going to be releasing something uh uh called reanin or renin I could care less which one you call it there all right and so all of all of this right if GFR increases if glomear filtration rate increases filtrate flow rate increases well filtrate flow rate increases this is going to lead to decreased reabsorption time in the loop of henley we want to hold on to things right so we need time to hold on to things so we want to slow down glomemeular filtration rate so we don't push things through too quick so and when we do push things through too quick we're going to cause our high sodium levels at uh in the filtrate and that's going to get sensed by that macula densa this guy's like "Whoa things are coming through to me too quickly slow down slow down." So that's going to be that feedback mechanism causing constriction of the aerant arterial right in here i love the way this is showing this in here this is some of the sympathetics that are making their way over uh to the kidneys remember there's really not parasympathetics there it's dominated by the sympathetics remember sympathetics are fight or flight so under the sympathetics under normal condition at rest renal blood vessels are dilated they're doing their thing they're autore auto uh autoregulated but when we need to hold on to blood right we're going to have various other activities that are going to go on there we have various hormones that I talked about remember the kidneys themselves secrete uh rein right there's going to be an antidiuretic hormone that's going to come from the posterior pituitary remember the the other name for the antidiuretic hormone is vasopressin because it's going to help constrict blood vessels there's also going to be uh angotensin 2 which rein is going to activate uh is ultimately going to activate the um amount of angotensin 2 i'll just say it right now rean is going to be responsible for uh taking angotensinogen angotensin one angotensin one through the lungs is going to become angotensin 2 and then it's going to have its work it's going to have several pathways you'll hear me say all that again and then although we don't see it here remember the adrenal gland right the adrenal gland in that zonia glomemeulosa of it it released something called eldoststerone aldoststerone is the major mineral corticoid and the mineral that it's bringing back here is sodium water follows the salt as sodium increases our blood pressure increases beautiful beautiful concept there the sympathetic nervous system under abnormal conditions such as extremely uh low extracellular volume low blood pressure our sympathetics our fight orflight kick in and our norepinephrine is released by the sympathetic nervous system and epinephrine is released from the adrenal gland causing the sympathetic vaso constriction which uh which increases the blood pressure constriction of the apherent arterial what's it do it decreases the glomemeia filtration rate so our blood v our blood volume stays higher all right if you get low on blood we might as well keep your volume higher so you don't get uh lower than you already are on blood so the renan angotensin aldoststerone mechanism that's something I've been trying to get into just a little bit all right it's the main mechanism of increasing our blood pressure when I say renin angotensin eldoststerone mechanism you might hear the term rasp pathway so three pathways of uh renin release and that's going to be by the the granular cells of the kidney you remember the granular cells green with green over here they're going to be uh releasing that renin of the kidney and we're going to have direct stimulation of granular cells by the sympathetic nervous system for release that's going to be one way we're going to have stimulation uh activated maculadens cells uh releasing uh because of the sodium chloride uh concentration that's going to activate the uh granular cells to release it we're going to have reduced stretch of the granular cells they're not getting stretch right there right what are they going to do they're going to release more rein/ renin so we need tons of that for controlling blood pressure right uh so but what's also interesting and we'll talk about it in depth later but Africans in comparison to Asians and Caucasians they have a lower rein uh that comes that comes through so their blood pressure is less rein uh dependent which is going to end up changing some of the drugs that we use to help control uh the African-American high blood pressure there's going to be several complications we talk about later as we're getting into it all right ACE inhibitors right ace stands for angotensin converting enzyme right angotensin converting enzyme so angotensin converting enzyme uh inhibitors what do they stop they stop uh ACE angotensin converting right so we're not trying to convert things and we don't convert things anymore we also have ARBs that go through arbs are angotensin receptor blockers we can see that angotensin 2 what's it doing it's uh coming through and we are then having its effect at constriction at the eerant arterial so what do the drugs we give do the drugs we give help us then dilate the apherent arterial by disrupting angotensin 2 right all the other pathways in the body that are working with blood pressure are working on the apherin arterial angotensin 2 is working on the uh on the apherin arterial the one that's going away and again remember if this guy constricts we're going to have a lot more filtration going through right here but ACE inhibitors angotensin converting enzyme inhibitors so we're stopping the production of angotensin 1 where there's no angotensin one there's no angotensin 2 then we have something called angotens tensin receptor blockers angotensin receptor blockers are going to be blocking the sites where angotensin 2 would be going so therefore it's not having its effect ace inhibitors are unique in the fact that they end up one of their side effects uh for a decent number of people but not all is that they cause a cough all right and that's what causes a lot of people to get off of them they are extremely effective because we found out that angotensin 2 is the ultimate protein in the pathway what do what did we learn to do we learn to block it directly through angotensin receptor blockers so the cough is gone again not everyone is affected by ACE inhibitors now as we talk through things the term prill right the term prill on the end of drugs I want you to think of that being with ACE inhibitors here's the pathway for the renit angotensin aldoststerone system and you are going to have this down so that you can answer my questions on uh the exams that come through what's going to happen we're going to sense uh that we have this sodium concentration change because of a blood pressure change so then those glamular meangio cells are going I'm sorry the ja glomemeular cells are going to release rein it's going to get into uh the vascular system and it's going to take angotensinogen and convert it to angotensin one angotensin 1 going through the lungs is going to get converted to angotensin 2 angotensin 2 itself has major effects angotensin 2 is the most potent vasoc constrictor known to man right andotensson 2 also goes to the brain specifically that posterior pituitary you learned about before and it's going to say release antidiuretic hormone remember the name for antidiuretic hormone also meant uh vasop prein all right so it's going to increase blood pressure it's also going to say hey drink water we're also going to say angotensin 2 is going to go through it's going to be saying "Hey you reabsorb more sodium right hold on to more water." And 2 is also going to go to the adrenal gland specifically the zonia glomemeulosa and say "Hey make more eldoststerone and release it which is then going to have its effects over on the kidney for sodium and water reabsorption." Team that's my time i'm going to pause this now uh so that you can have time to digest this before I go into the next lecture with