Lecture22 Urinary

hi everyone this is lecture 22 urinary system so the urinary system is the system that includes the kidneys as their working unit and then the rest of the system that releases urine after the kidneys produce it so I'm going to introduce you to the urinary system also called the renal system renal refers to kidneys we're going to talk about the kidney function and the regulation of the kidneys through that will talk about the processes of glomerular filtration tubular reabsorption tubular secretion and plasma clearance as the kidney is working so just a review of the kidney the kidney has a large blood supply which branches throughout the middle of the kidney which is the medulla and the outer portion of the kidney which is the cortex the working units of the kidney are located through the cortex and the medulla and they will produce urine urine then drop by drop will enter into the renal pelvis and exit out of the ureters from the ureters the urine will enter the bladder where it is stored and then out the urethra we'll talk about the differences between the male and female urethra when we get to the reproductive lecture which is our next lecture so the urinary system is made up of the kidneys the working unit of the kidney is the nephron and after the nephrons and the kidneys produce urine urine will exit the kidneys through the ureters then to the bladder and then out of the body through the urethra so this is just an overview of the kidneys within the body and I want to emphasize here the heavy blood supply that enters and leaves the kidneys so the kidneys are the primary organs of the urinary system at less than 1% of the total body weight they receive twenty to twenty-five percent of the total cardiac output in other words they have a huge blood supply which enters through the renal artery the funk the functions of the kidney include maintaining blood volume maintaining fluid and electrolyte composition of the blood that is balancing the water and the ions within the blood maintaining acid-base balance eliminating metabolic wastes and other substances activating vitamin D which helps with calcium and phosphate absorption in the small intestine and production of certain hormones the kidneys can produce EPO which increases red blood cell production they also produce remin which product which is part of the renin-angiotensin-aldosterone system for water and salt conservation so what exactly is urine urine is a fluid waste product that is produced by the kidneys it normally contains water ions nitrogenous waste and small soluble compounds basically urine is a filtrate of the blood so the blood enters the kidneys is filtered and whatever substances the kidneys decide to keep out of the blood will enter the urine whatever substances are necessary will be returned to the blood as the blood returns to the body so the composition of urine will change as a function of blood and kidney regulation so the urine should not contain components of the blood that are necessary for the basic function of the blood it should not contain blood cells it should not contain the large proteins in the blood which help to maintain the osmotic of the pod and presence of blood cells and large proteins could indicate damage to the kidneys so the nephron is the working unit of the kidney the nephron is what actually does the work of deciding what should stay in the blood and what should be removed from the blood to enter the urine so the nephron actually produces the urine through this process and there are over 1 million nephrons in each kidney nephrons will remove exchange and add materials to and from the blood in order to regulate blood composition so what i want you guys to ask as you're going through the urinary system are two questions what should stay in the blood and what needs to be removed from the blood so the blood will enter the kidneys and the regulated blood leaving the kidneys will return to the body so what do we need to maintain in the blood as the nephron begins to filter and act on the blood and then the blood and in is also going to have waste that needs to be removed so I want you also to ask what should leave the blood and exit the body so think about waste and other products that need to leave the blood and how can the kidneys do that so overall this large blood supply is going to enter the kidney and nephron by nephron little little by little the kidneys will remove waste regulate the fluid composition regulate the ions and regulate the acid-base composition so that the blood leaving the kidney is regulated and filtered and then that blood will be returned to the body and general circulation whatever is in excess in the blood that needs to be removed then will exit out and be excreted through the urine so I want to take a moment and this is important please get out a piece of paper and we're going to draw the anatomy of the nephron together okay so entering the nephron is a large blood vessel called the a Ference arteriole the afferent arteriole and branches into a tuft of capillaries that looks like a ball of yarn that tuft of capillaries is called the glomerulus then the blood exiting the glomerulus will leave out the efferent arteriole and that will continue to branch around the kidneys in a group of capillaries called the peri tubular capillaries surrounding the glomerulus is a large capsule which is the start of the nephron so that capsule is called Bowman's capsule and it's lined with epithelial cells and it has a hollow center so together Bowman's capsule plus the glomerulus is called the renal corpuscle so again renal corpuscle is Bowman's capsule plastic glomerulus so what's going to happen is that the blood is going to enter the efferent arteriole and travel through the glomerulus and it will first be filtered and that filtrate is going to enter Bowman's capsule from there there is a series of winding tubules I'm just going to draw this way we call the proximal convoluted convoluted four winding to fuel and then there's a long dipping down to Buell makes a big loop and we call that the loop of Henle so the urine filtrate is going to travel through the proximal convoluted tubules and then down the loop of Henle and then back up the loop of Henle so we call this the descending limb of the loop of Henle and the a sending them up for loop of Henle from there we enter into another structure that is winding and it's further away in terms of how long the filtrate has traveled from Bowman's capsule so this we call the distal convoluted tubules and I abbreviate these as PCT proximal convoluted tubule and DCT distal convoluted tubules then the last stop before the urine exits out the renal pelvis is called the collecting duct so the filtrate will travel up the ascending limb of the loop of Henle through the distal convoluted tubule and then down the collecting duct where the urine will exit out the body what I want you to notice is that I have drawn the peritubular capillaries up here that's for simplicity it turns out that the peritubular capillaries are winding all around all around the nephron structure so they're really everywhere so I should really draw them all over the place and so I want you to remember them that there will be constant exchange back and forth between the peritubular capillary and the urine filtrate that will happen all throughout the nephron so we have the afferent arteriole which enters the glomerulus the glomerulus then puts filtrate into you Bowman's capsule the blood will leave the efferent arteriole and the filtrate will enter the proximal convoluted tubule from the efferent arteriole then the blood will enter the peritubular capillaries and the filtrate will continue down the loop of Henle which is wrapped with peritubular capillaries for the loop of Henle you have the descending limb which goes down the loop of Henle and the ACE ending limb which goes up the loop of Henle from there is the distal convoluted tubule and the collecting duct so look over here and you'll see a more anatomically correct diagram so the picture that I just drew for you is with relation to how the filtrate flows from start-to-finish what you now need to do with the picture is take that nice linear flow take the distal convoluted tubules and wrap it around so it goes back and touches the efferent arteriole and that's the picture that you see here so here's your a ferrand arteriole and let's just follow the path of the filtrate it's going to enter Bowman's capsule and then a series of winding tubes which are the proximal convoluted tubules and then it's going to go down the descending limb of the loop of Henle and up the a sending limb now here's the distal convoluted tubules twists back and touches the efferent arteriole so all of this is distal convoluted tubules traveling through until we get to the final exit which is the collecting duct and then the urine will exit the bottom as of the renal pelvis so this is basically how I drew it for you but remember this is a linear path as if we've stretched out the nephron to go from start to finish anatomically we need to take this end the distal convoluted tubules and twist it back over so that it touches the afferent arteriole and we'll talk about the significance of that and its regulation so this is a summary diagram for your reference for later now let's talk about what is actually happening throughout these tubules there are three main processes in the nephron that regulate blood and in the process of regulating blood produced the urine the first is glomerular filtration glomerular filtration is separation of big from small so this is separation of cells and large proteins those should stay in the blood from the plasma and whatever is dissolved in the plasma basically small molecules so the plasma will enter the nephron and the cells and the large proteins will stay behind that is a filtration process then the second process is tubular reabsorption reabsorption means that you're taking fluid or substances from the filtrate and putting it back into the blood the last process is tubular secretion where something that is in the blood that has not yet been filtered out will be put into the blood selectively to make sure that that particular waste substance is removed from the blood and out the urine so first let's talk about glomerular filtration lemare Uhler filtration is what I refer to as the pasta strainer so think about a pasta strainer right or some people call it a colander I guess it depends on where you're from and it's a pasta strainer have lots of little tiny slits in the bottom right and you dump your your pasta or your soup or whatever it is you're trying to filter and all the big stuff the pasta stays behind and what ends up in the pot is the fluid and anything small enough to fit through all those tiny little slits so this is what happens with glomerular filtration so there are these tiny little filtration slits that I'll show you in a second that allows small molecules through but keep the large molecules namely the proteins and the large cells in the blood so the blood is going to enter in the afferent arteriole and pass through the glomerular membrane so this is at the glomerulus what do we want to stay in the blood we want large proteins and cells to stay in the blood so they will stay and they will exit the efferent arteriole what do we want to enter into the filtrate so we can begin to regulate it well basically everything else we know we need to keep large proteins in cells we're not sure about what's left in the filtrate so we're going to put everything that's small enough into the tubules so what should go into the tubules is going to be water ions small molecules anything that is small enough to fit through the tiny slits in the filtration membrane so these are going to enter the filtrate at Bowman's capsule so the afferent arteriole will bring the blood in and then the membrane at the glomerulus is going to act like a pasta strainer it's going to keep the large cells and proteins which would be the pasta in this example back in the blood and allow the fluid and small molecules to enter into the kidneys so they can now regulate it so this is what the glomerular membrane looks like so these are the openings and the spaces that the small molecules will have to travel through to get into Bowman's capsule there are three components of the glomerular membrane that will filter the blood through there's the glomerular wall the glomerulus is a capillary so the wall of the capillary is just like any other capillary simple squamous epithelium but these capillaries are unusual these are a particular type of capillary that contains large pores those large pores are called fenestrations ven astro means window so these are large pores or holes that allow some molecules to pass across the capillary wall towards the filtrate then there's a small basement membrane the basement membrane is a glycoprotein gelatinous layer that is also full of collagen so this layer will act like kind of like a cheesecloth so you add little holes and the capillaries that let some small molecules and fluid through and then you have a basement membrane that will let even small smaller molecules through leaving some of the larger molecules behind and then finally we have one more level of slits and these are actually in the capsule so there are these cells called podocytes that wrap around the capsule and one photo site will have sort of its cell body here and then these Big Foot processes so pod or Poteau refers to feet this is big stretching out feet and they will link together and make these slits that lay across the capsule so these little slits will act like another second pasta strainer and they will keep large molecules out of the filtrate and only allow fluid and small molecules through so here is a picture of how all of that is happening but I think that it would help you guys if we drew it out so let's draw it out so we are here where the blood has entered the afferent arteriole and is now going to be pushed out of the glomerulus into Bowman's capsule everything went States behind in the blood will leave the efferent arterial so let's zoom in here the glomerulus so we have the 1/3 arterioles coming in and then capillaries I'm not going to draw the whole tuft of capillaries these capillaries have pores in them or fenestrations so they are fenestrated capillaries so some small substances and fluids are going to be able to get through those fenestrations they will also pass through a basement membrane and then they will enter the capsule which again have these filtration slits covering them from the podocytes so the podocytes don't make up the capsule the podocytes cover the capsule and create these slits which will have one more passive filtering such that what enters the capsule is going to be fluid and small molecules and those will continue as the filtrate that will enter the rest of the nephron what stays behind will be blood cells red blood cells white blood cells and proteins large protein albumin proteins etc and those will exit out stay in the blood through the efferent arterial so the blood keeps large cells and protein the fluid and small molecules enter the filtrate and this is the process of glomerular filtration so here is a nice diagram from the book showing the afferent arteriole which then becomes the glomerular capillaries and the glomerular capillaries are surrounded by podocytes so you have the fenestrations we have the demonstrations and the capillaries the basement membrane surrounding the capillaries and then the podocytes forming the filtration slips from there whenever is able to pass through those three layers a filtering will enter this capsule drawn here in yellow and become the filtrate that goes into the rest of the nephron the blood will continue to pass through the efferent arteriole and continue to be regulated as it crosses the remainder of the nephron so there's a a actual picture of the glomerular membrane with the fenestrations of the capillary the basement membrane and the podocytes that form the slips here's a really cool picture of a photo site these are neat cells so there's the cell body of the photo site and then you can see how it stretches at least finger-like processes and then they intertwine with other photo sites to form these filtration slits so I hate to do this to you guys because we just did a net filtration pressure for capital areas and bulk flow but since you did that you guys should be experts now so we have to now talk about something similar to capillary bulk flow and this is glomerular filtration pressure so glomerular filtration this process of getting filtrate into Bowman's capsule is regulated by various pressures at the glomerular membrane so the capillary blood pressure will be the main driving force just like in bulk flow where the arterial and venous venule blood pressure where the main driving force is there same thing here but we also just like bulk flow we'll have opposing forces which are the osmotic pressure so we're going to have our outward pressures driving fluid out of the capillary and we will have our inward pressures driving fluid back into the capillary so let's just draw this briefly to give you guys an overview of this type of filtration pressure and if you didn't understand capillary bulk flow this will be a similar process so this may help you understand that as well so this is glomerular filtration pressure and what we want to look at to get the glomerular filtration pressures is the sum of outward pressures minus the sum of inward pressures just like we did for bulk flow so our outward pressures for glomerular filtration are going to be hydrostatic from the capillaries our main inward pressure is going to be osmotic pressure in the capillaries we will also have a hydrostatic pressure that is from the filtrate oops sorry an osmotic pressure that is from the filtrate that will drive fluid into the filtrate we will also have a hydrostatic pressure from the filtrate that will drive fluid away from the filtrate and into the capillaries so it looks like this we have the glomerulus and then we have Bowman's capsule so for the glomerulus the major pressure that will be driving fluid out is going to be blood pressure so this is a hydrostatic pressure that is forcing fluid out of the glomerulus and we call this the hydrostatic pressure of the glomerular capillaries in other words pee glomerulus or pressure of the glomerulus this is approximately a positive fifty five millimeters of mercury there will also be within the blood an osmotic pressure with all of the proteins that are in the blood and solutes drive fluid towards them so this is going to be an inward pressure due to solutes driving fluid into the glomerulus so this is going to be the osmotic pressure of the glomerulus and that pressure turns out to be about negative thirty millimeters of mercury we also have hydrostatic pressure so there is fluid in Bowman's capsule that also drives and pushes fluid back towards the blood that hydrostatic pressure of the filtrate is about negative 15 millimeters of mercury and we're just going to call that HP of Bowman's capsule and that is about negative 15 the last is osmotic pressure that would drive fluid into Bowman's capsule if there was damage to the glomerular filtration membrane and somehow blood and proteins got into Bowman's capsule that would drive fluid with an osmotic pressure sucking fluid towards the solutes but in this case there's no pathology the blood and proteins stay in the blood so the osmotic pressure of the filtrate is zero so now I just take our outward pushers and we subtract our inward pressure so we have 55 minus 30 plus 15 45 and our glomerular filtration pressure is going to be about 10 millimeters of mercury into Bowman's capsule out of the blood to bone Axl so why do we care about this we care about this because ultimately the blood pressure that is coming into the glomerulus is driving filtration and if we want to regulate filtration the easiest way to regulate that is to change the blood pressure coming in so the rate of glomerular filtration is very important clinically for assessing the health of the kidneys assessing kidney disease and looking at kidney failure because this is the first pass of fluid entering the kidneys and without glomerular filtration or with low glomerular filtration the kidneys don't have any fluid to work on so looking at the net filtration pressure we need to take into account how much blood pressure is coming in and the basic properties of the glomerular membrane so the total filtration rate or the total amount that is being filtered through the glomerulus will be the net filtration pressure that we just calculated multiplied by a factor called K which represents a properties of the membrane so the properties of the membrane such as the size of the pores and the capillaries the size of the filtration Flitz of the Poteau sites are also modifiable in addition to the pressures and that will give us our total GFR the total for the entire system daily average GFR is about 115 to 125 milliliters per minute and you will if you move forward clinically use glomerular filtration rates as a way to assess the health of the kidneys so as I said the regulation of GFR can be altered by regulating blood pressure there are other ways to regulate GFR you can regulate the protein concentration in the blood that will affect the osmotic pressure pulling fluid back into the blood so that will oppose filtration you can regulate your level of hydration which will affect the pressure in the glomerulus and the pressure in the filtrate as you increase water the hydrostatic pressures will increase GFR can also be affected by obstruction in the urinary tract so obstructing the obstructing the urinary tract can affect the pressure in the capsule but the main way to affect GFR is through blood pressure or mean arterial pressure this is the variable that will cause the biggest changes so there are two ways that the kidneys can compensate and change mean arterial pressure one is through local mechanisms which we call auto regulation there's two ways the myogenic and two the local area feedback another is extrinsic or outside regulation through the sympathetic nervous system so the idea here is that as you change the blood pressure coming in you will ultimately change the glomerular capillary pressure which will ultimately affect the hydrostatic pressure and the net filtration pressure if you increase all of those pressures by increasing arterial blood pressure you can increase GFR and vice versa if you cut off the blood flow or the blood pressure to the glomerulus you will decrease GFR so first auto regulation is the main way that kidneys sort of on a moment-by-moment basis maintain constant GFR so this is to basically as the arterial blood pressure changes the kidneys will regulate GFR to compensate for that to maintain the same pressure within the glomerulus no matter how the blood pressure is chained so if GFR is too high sense that it is too high then the afferent arteriole will be closed off through vasoconstriction not fully closed off but blood flow will be decreased and local blood flow will slow down to the glomerular capillaries and there will be less GFR if it's found that GFR is too low the afferent arteriole will be dilated and now increase flow to Bowman's capsule and get more filtrate through so the first way to do this is oh I guess I should show you guys this I instead of leaving my hands okay I'll show you the diagram sit so if we go from a normal size to Veysel construction that will decrease blood flow to the glomerulus and ultimately decrease GFR if we however go from a normal size to a dilated efferent arteriole that will increase blood flow to the glomerulus and increase GFR so the first way to do this is the myogenic mechanism the afferent arteriole actually automatically constricts if it is stretched so if mean arterial pressure in the body increases that will stretch the afferent arteriole the afferent arteriole will Veysel constrict to try to keep GFR constant so rather than fluctuating continuously as the blood pressure changes in the body there is auto regulation within the kidneys to maintain a ferrant arterial pressure despite what changes might be happening in the body so if they're over stretched then they will they still constrict to bring GFR back down the second way that the kidneys can do this locally is through something called two below glomerular feedback remember when we talked about the distal convoluted tubules wrapping back around and touching the afferent arteriole well that's what this picture is showing so if you're actually looking at here is a piece of the distal convoluted tubules this is one of the last stops of the filtrate before it leaves the kidneys so this is a very handy place for the kidneys to assess how are things going in the filtrate is the filtrate actually successfully being formed or do we need to give it more time so at this point there are specialized cells in the distal convoluted tubules that will sense the filtrate and we'll talk to the afferent arteriole those specialized cells in the distal convoluted tubules that touch nearby the afferent arteriole are macula densa cells within the aether and arteriole we also have specialized cells that will listen to the macula densa and these are called the granular cells together this whole apparatus of the distal convoluted tubules and the efferent arteriole communicating about how the filtrate is doing its job is the juxtaglomerular apparatus so here is an example of how it works if we have high pressure in the glomerulus the macula densa will sense that there is high salt and high fluid flow through the filtrate so if the filtrate is moving too fast it will sense a lot more salt and fluid in a particular time than normal it will then release ATP and adenosine and the granular cells will sense that ATP and adenosine and Veysel constrict so if pressure is too high in the filtrate that will go down the line and get sensed in the distal convoluted tubules iva macula densa they will then tell the granular cells to cause vasoconstriction in the æther and arterial to slow down the flow and bring GFR back down to normal so here's a su min of that juxtaglomerular apparatus and this is a nice picture which shows basically where we are in the nephron so here we have our glomerulus the filtrate let's say the filtrate got very high and that passed through the proximal convoluted tubule passed through the loop of Henle and then also stayed high in the distal convoluted tubules at this point that that high pressure high salt high fluid movement travels through the distal convoluted tubules can talk to the afferent arteriole and slow down GFR to balance the last way to regulate GFR is through the sympathetic nervous system so we've talked a lot about sympathetic nervous system regulation of cardiovascular changes what does the sympathetic nervous system due to blood vessels in general do you remember vasoconstriction so this is no different the afferent arteriole when it gets sympathetic nervous system input will Veysel constrict and it does that to shut down or slow down GFR what does the sympathetic nervous system overall do to the urinary system now this should make sense based on what you know about what the sympathetic nervous system does the sympathetic nervous system does not want the body to be producing high amounts of urine why because you're running from the barre right so you can't be urinating and and producing urine and spending energy producing urine when you're trying to put energy into your brain and skeletal muscles to run from the barre so the sympathetic nervous system will actually slow down blood flow to the glomerulus by Veysel constricting the efferent arteriole it's going to constrict the afferent arteriole slow down GFR and slow down urinary production also turns out to have an effect on nearby cells in the juxtaglomerular apparatus and Poteau site contraction that will decrease the size of the filtration slips and prevent entry of fluid and small molecules even further from entering the tubules so we're going to decrease the filtrate rate by decreasing blood flow into the nephron we will also decrease the filtration mechanically by closing down the filtration membrane over all the sympathetic nervous system decreases GFR so this is a summary of the sympathetic nervous system regulation so essentially if arterial blood pressure increases then excuse me let's start back up here so essentially if arterial blood pressure is too low in the whole body then now BTEC detected by the nervous system that will increase sympathetic activity which wants to increase cardiac output and increase total peripherals of resistance to bring blood pressure in the whole body back up by doing that it will increase vasoconstriction in order to divert blood to the important areas and increase totally arterial blood pressure Vasil constricting locally at the kidneys is going to decrease GFR to decrease urine output that will ultimately lead to less loss of fluid and salt and increase arterial blood pressure long term okay do you guys understand glomerular filtration if not pause go back and review your notes before we get to tubular reabsorption so now that we have gone through the filtrate process we're now going to take that filter eight and selectively decide what gets to stay and what should go so tubing the reabsorption is a selective process of taking needed substances from the filtrate and putting them back into the flood so remember that the filtration process through the filtration membrane was not specific to any molecules it was only a size filtration so anything small and fluid is now in the filtrate including a lot of things that the body needs so the glomerular filtrate is going to contain a lot of fluid ions and small molecules from the blood that the blood needs back so starting with the proximal convoluted tubule now we will selectively transport the valuable substances that the blood needs back to the peritubular capillaries those will be then returned to the blood and returned to the body anything that the tubules don't recognize they don't know anything that is in excess that will stay in the filtrate and exit Azure so we're going to take the filtrate through the remaining tubules and return valuable substances to the blood anything then that is not necessary to be returned to the blood will stay in the filtrate and enter as waste so for normal GFR at 125 milliliters per minute about 124 milliliters per minute is returned to the blood so this is 99 percent of water 100 percent of sugar for nutrients 99.5 percent of salt will all be put back into the blood so the body knows water sugar salt that needs to go back but what will exit and leave the body will be any excess iron ions urea and toxins will become concentrated in the filtrate so we're going to do reabsorption by location and talk about the processes in the remaining tubules so first the proximal convoluted tubules the proximal convoluted tubule is going to reabsorb a lot of salt a little bit of water some chloride all the glucose possible amino acids phosphate urea and potassium we'll talk about secretion in a moment and control as we go through the loop of Henle is going to reabsorb about 25% of the total salt about 15% of the total water and some chloride the distal convoluted tubule and collecting duct will reabsorb more salt about 8% of the total more water and more chloride so you may notice as you look at these three lists that the missouri majority of reabsorption happens right away in the proximal convoluted tubules and then after that through the loop of Henle the distal convoluted tubule and collecting ducts it's really just salt and water balance basically the concentration of the urine that is being altered so for this we need to talk a little bit about cellular transport that is happening in the tubules so reabsorption happens through the process of selectively transporting substances from the tubules into the blood so we need to draw this out a little bit just to give you guys a picture so we finished filtration which happens between the glomerulus and Bowman's capsule and now the filtrate is moving into the proximal convoluted tubules of reabsorption is going to happen so let's zoom in here on the cells within the proximal convoluted tubules so what we have in the proximal convoluted tubule our epithelial cells lining then we have the lumen where the filtrate is entering so the filtrate coming in the epithelial cells of the proximal convoluted tubules you're going to have some fluid and then from there we'll have the peritubular capillaries winding all over the tubules and waiting to get their substances back so one is already currently in the peritubular capillary is from the filtration process already in the peritubular capillaries will be blood cells and proteins okay so this is all blood it came from the efferent arteriole which came from the glomerulus which came from the afferent arteriole right it's just going to be densely filled now with proteins and cell there will be some fluid because not all the fluid enters the filtrate but in the filtrate now we have the fluid and small molecules when we want to return important substances through the epithelial cells of the proximal convoluted tubule through to the interstitial fluid of the proximal convoluted tubules and then back into the blood so how is selective transport achieved what do we use think back to our cellular transport lectures that you guys did at the beginning of this master we need some protein channels so we're going to have channels found the tubular lumen to the tube you'll epithelial cells we also need to have channels from the basolateral membrane or this base membrane to the interstitial fluid and then substances can enter the peritubular capillaries so this is all re absorption and reabsorption is the process of returning needed substances from the filtrate back to the blood and it requires selective channels so let's look at some specifics of this type of transport so reabsorption can be passive or active well you guys to think back to your membrane transport lectures and this is the same idea so a passive transport is when you have no energy required to pass from the tube you'll to the blood so we're getting across the membrane the phospholipid bilayers of the tubules cells in some cases you don't need energy to do that they can just follow their gradients from high to low in other cases you have active transport where ATP is required for at least one step this is secondary active transport where the sodium gradient will be set up by a sodium potassium pump and then a sodium gradient will be used to transport other material so the sodium potassium ATPase pump is present in the basolateral membrane throughout several of the tubules the sodium gradient then is maintained by pumping sodium out of the tubules and keeping sodium low inside the tubules cells this will be the driving force for sodium to leave the tubules and we can use that sodium gradient for co-transport of important molecules so for example glucose amino acids water will follow chloride will follow and then the change in concentration of urine can also be done through sodium use use of sodium gradients so removing sodium will also remove water from the filtrate and finally this can also be done to regulate blood volume so if we change the sodium content in the blood we can change the water content of the blood and we'll do this through hormonal mechanisms to regulate blood volume and blood pressure so this is what it looks like you have the sodium potassium pump in the basolateral membrane and that will keep the sodium levels inside the tubular cells low that ensures that if you have any sodium in the filtrate it will move from high to low into the tubular cells and then you can piggyback on that sodium movement to bring in glucose amino acids etc so T max is the maximum amount of movement across the membrane for any given molecule so we also call this renal threshold so when a plasma concentration of a substance exceeds the ability of the carriers then it will be in excess and it will stay in the filtrate and be lost in the urine here's an example glucose has a fairly high renal threshold because it has a high T Max value so up to approximately 300 milligrams per 100 mils in the blood of glucose you will get constant filtration and reabsorption so glucose will enter the filtrate glucose will be returned to the blood all the way until you get to 300 milligrams of glucose per hundred milliliters of blood once you hit that point you've maxed out your channels and no further reabsorption beyond 300 MiG's per mil can occur once you get there anything above that will be excreted in the urine so as T max is reached reabsorption cannot increase and the remainder of glucose will be excreted it's actually quite a high value so even if you have a giant chocolate cake for dinner the glucose will be entirely reabsorbed and you won't see any sugar in your urine that will only be in pathological cases where you reach extremely high high levels of plasma concentration of glucose in the blood because of say diabetes or other conditions other molecules however have a low threshold that means they normally don't have a lot of channels or there normally aren't any channels in the tubular membrane so phosphate is an example of that any excess phosphate in the blood will be quickly eliminated in the urine because there are very few phosphate channels in the tubules hormones however can adjust the renal threshold for phosphate if more is needed in the body and that will simply be done by increasing phosphate channels in the tubular cells so after these sodium gradients are established other molecules can follow water will follow flowing through aquaporin channels where 65% of water will be recovered by the end of the proximal convoluted tubules 15 percent will be recovered by the loop by the loop of Henle the remainder of water will be regulated by hormones in the distal convoluted tubule and the collecting duct chloride will also follow sodium following the electrical gradient created by the sodium gradient as the water leaves the filtrate your will become concentrated and about 50% will be of urea will be reabsorbed due to its small size so here's an example of how it works for water so here we have the sodium moving through because of its gradient water will then follow the sodium as long as there are water channels present for the water to move in so there are water channels in the tubular lumen so water will enter the tubules cells and there are water channels in the basolateral membrane so water can then eggs with the shoe Buell's and go into the blood here's just a summary of where we are so far where for normal glomerular filtration rate about a hundred and twenty five millilitres of filtrate will enter the proximal convoluted tubules from there we will have active transport of sodium and water will follow along with that active transport of sodium other molecules such as glucose and amino acids will also follow and be reabsorbed into the peritubular capillaries later on down the line as the urine gets more concentrated passive diffusion of urea can also occur so what's left anything that is not actively reabsorbed left in the filtrate will be excreted in the urine this will include molecules that hit their T Max and molecules that are small enough to enter the filtrate at the glomerular membrane but do not have transporters for reabsorption so this will include wastes like uric acid wastes creatinine least phenol and other toxins that don't have transporters to return to the blood so the regulation of tubular reabsorption have been through hormones first the renin-angiotensin-aldosterone system affects sodium reabsorption and increases the amount of sodium that returns to the blood a and P and B n P will oppose that and decrease sodium reabsorption and then water re-absorption will happen mainly through the action of ADH or vasopressin ADH will increase water reabsorption and maintain blood volume so first for the Rast pathway so the renin-angiotensin-aldosterone system the net effect is to increase sodium reabsorption and this will be done through mainly the collecting duct and the distal convoluted tubule this happens because of the granular cells in the afferent arteriole and the macula densa cells in the distal convoluted tubules so the granular cells have their own receptors that will sense blood pressure and if blood pressure is too low they will cause renin to be secreted the macula densa have sodium chloride receptors and the sodium chloride gets too low because ultimately filtration and blood pressure was too low then they will also send signals to secrete renin this can and finally be triggered by sympathetic nervous system innervation to the granular cells as well so here's how it works and let's draw this out so if the granular cells sense that blood pressure is too low or if the macula densa sense that sodium chloride is too low or if the sympathetic nervous system simply is triggered by stress or low blood pressure then renin will be released so remin is actually an enzyme it's an enzyme that converts a molecule called angiotensinogen into angiotensin one angiotensin one will travel through the blood and be converted by another enzyme called ace which is present in totally randomly present in the lungs so ace will convert angiotensin 1 to angiotensin 2 and that will stimulate several things but ultimately it's going to stimulate the adrenal cortex to produce aldosterone yes angiotensin 2 has some of its own actions it can increase vasoconstriction in the body it can also stimulate thirst but ultimately it's most important effect is to stimulate the adrenal cortex the adrenal cortex then will produce aldosterone aldosterone will increase sodium channels specifically in the tubular lumen of the collecting duct and the distal convoluted tubules will ultimately increase sodium reabsorption which will allow for increase water and increase blood volume an increase in blood volume will increase blood pressure to counteract what was initially sensed as low blood pressure so ultimately the wrasse pathway is present to maintain blood volume and the kidneys are a place that can sense small changes and large change in blood volume and send signals out to the rest of the body to help to increase blood volume those signals will ultimately act through the kidneys to increase sodium reabsorption and water will follow so I want you to notice how many body systems are involved in this blood volume regulation this pathway is absolutely essential to life and deficits in aldosterone can be life-threatening so ultimately the liver produces angiotensinogen running from the kidneys converts back to angiotensin one ace from the lungs converts it to angiotensin 2 angiotensin 2 signals to increase thirst and vasoconstriction but ultimately signals to the adrenal cortex to increase aldosterone aldosterone then acts on the kidneys to increase sodium which will conserve salt and ultimately conserve water in the body and that helps to correct the initially low blood pressure that was felt and sensed by the kidneys so aldosterone ultimately regulates so Neum and the levels of sodium in the blood increase aldosterone will increase sodium reabsorption and decrease sodium excretion it also has an effect on potassium secretion and if we go back you will see that it not only insert sodium channels into the lumen it also increases sodium potassium pumps so the sodium potassium pump is twofold it helps to maintain the gradient so that sodium will enter the tubules cells it can also help to get rid of potassium and secrete potassium out of the cells we'll get to secretion in just a moment a and P and B and P oppose aldosterone by inhibiting renin ultimately this will decrease sodium reabsorption and decrease blood ball these are triggered by stretch of the heart muscle indicating the heart has been overloaded by too much blood volume and they will then act to decrease blood volume and blood pressure so now we need to talk about how urine gets concentrated beyond the reabsorption processes so we're done with reabsorption now we're going to get to urine concentration and secretion so urine is concentrated because of the gradient that is set up by the loop of Henle so the loop of Henle establishes and maintains an osmotic gradient that can be used to facilitate water and sodium reabsorption this ranges from the upper cortex values of the loop of Henle 300 milliosmoles to the lowest medulla values or the deepest medulla 1200 milliosmoles this is created by something called a counter-current exchange where fluid moves down and up the loop of Henle in the opposite direction of the way that fluid is moving through the Vasa recta so what we have is a different level of channels and the descending and ascending limb of the loop of Henle the descending limb of the loop of Henle has high aquaporins where water will leave the a sending limb has high sodium and chloride transport where sodium and chloride will leave so if we break down the kidney into cortex and medulla the proximal convoluted tubule and distal convoluted tubules will be in the cortex and it is only the loop of Henle that stretches down into the medulla so at the top of the loop of Henle and within the proximal convoluted tubules they are sitting in fluid that is 300 Nili osmolar that is isotonic to the blood as you dip down into the medulla the loop of Henle gets into further and further highly concentrated environment so you can see from this diagram how that Anatomy works so the proximal convoluted tubules in the cortex the loop of Henle dips down into the medulla where it gets more and more concentrated outside of the loop of Henle and then goes back up towards the cortex where it goes to the distal convoluted tubules back and I so osmotic conditions and then the collecting duct dips back down through the medulla and this is important for actually using the gradient that's established so partly this works because of the different composition of channels that are present in the filter and in the loop of Henle so high water channels through the descending limb means that a lot of water leaves out of the descending limb that will concentrate the filtrate and pump water out so the filtrate will be highly concentrated by the time it gets to the bottom of the loop of Henle and then that highly concentrated filtrate will start to go back up the loop of Henle and sodium chloride or salt will be pumped out of the filtrate from there that sodium chloride can be pumped in excess such as it actually can become hypotonic or very low salt concentration so from the proximal convoluted tubule Dome the filtrate can lose water and from the bottom of the loop of Henle up to the distal convoluted tubules rate can lose salt to become more dilute but it will be a lower volume dilute urine so the dilute urine will enter the distal convoluted tubules and the osmotic gradient in the medulla will be maintained and used by the distal convoluted tubule and the collecting duct to increase water reabsorption so I think we need to draw this out even though you guys be patient I know we're getting towards the end of the lecture but let's draw it up so the proximal convoluted tubule is going to be in the cortex so here's the cortex of the kidney and then the loop of Henle dips down into the medulla and back up towards the cortex so the medulla because of the way that the blood vessels surrounding the loop of Henle are twisting and turning and moving in different directions with respect to the fluid ultimately this gradient is set up such that you have 300 milliosmoles extracellular fluid outside of the loop of Henle at the top near the cortex and that gets more and more concentrated in the medulla I will be honest with you guys and that I have been teaching this for a long time and I have read many text book accounts of this counter-current exchange and I have never found anything that satisfactorily explained this counter-current exchange and why it works and how its set up if you guys find something let me know let's just accept that the counter-current exchange produces this highly concentrated environment that the loop of Henle dips down into so the filtrate is going to enter the loop of Henle and travel down and as I says is going to lose water that's going to decrease the volume of the filtrate and increase its concentration as it then moves up the ascending limb it's going to lose sodium chloride that will cause it to be dilute or low solute by the time it gets back to the distal convoluted tubule what's cool about this is that this can be regulated such that at the end the collecting duct can now use this gradient so it's actually not in the loop of Henle that the concentration is important the loop of Henle is important for the setup so the loop of Henle sets up the gradient and the collecting duct is going to use the gradient so now in the collecting duct we're going to have hormone regulation to take the final filtrate before it exits out the urine and concentrate or change how much sodium and how much water stays in the filtrate and how much remember it's going to go back to the blood so the hormones that we just talked about first we have aldosterone if we increase aldosterone we will increase sodium back to the blood now here's our final hormone which is ADH ADH is going to increase water back into the blood so that both aldosterone and ADH will cause volume loss and concentration loss in the urine that is in order to retain the sodium and water using the blood so hormones will regulate the collecting duct aldosterone and ADH to increase sodium retention or reabsorption and increase water retention or reabsorption and that ensures that the urine is low volume and we don't lose too much water or salt so low salt so the regulation of water is going to happen by using the osmotic gradient in the doula and the use of ADH or vasopressin to insert aquaporins into the collecting duct this is a graded response that can slightly increase our decrease based on need and this is why if you drink a lot of liquid you will have a high volume of dilute urine and if you do the opposite if you dehydrate yourselves which is most of us right be honest guys we don't drink enough water you will have a low volume of very concentrated urine so up to 20% of total water reabsorption can be increased at the distal convoluted tubules and the collecting duct what's interesting is that caffeine and alcohol block ADH so you will get an increase in urine output even if you're dehydrated from the caffeine the alcohol and this doesn't do much for the body and that's why you can get hangovers and migraines from caffeine and alcohol so here's how it works the ADH will increase aquaporins in the lumen so here is the vasopressin or ADH which is being released from the blood where does it come from do you guys remember the posterior pituitary so it's sent from the posterior pituitary into the bloodstream it will bind to receptors in the collecting duct and through a second messenger system will increase insertion of aquaporins when it does that more water will enter the tubules cells and that water will then be able to move from the tubular cells into the blood so the filtrate has normally a concentration of about a hundred milli molar as it and enters the distal and and distal and collecting distal convoluted tubules and collecting ducts and if you don't have vasopressin that high-volume dilute urine will be lost this is what you see with alcohol intake and caffeine intake where you get a lot of dilute urine clear looking urine and high volumes of it exiting the body with vasopressin water is removed from the filtrate and returned to the blood such that urine becomes more concentrated and here your textbook is showing you it will be a darker yellow color and you will have less volume of it because that water will be returned to the blood and it won't be lost in the urine okay we're almost there guys a little bit on tubular secretion and then we'll be done so tubular secretion is the process now of taking anything that was in the blood that hasn't yet been eliminated so this is a last step to make sure okay do we have everything we want in the blood have we gotten rid of everything out of the filtrate so tubular secretion is an active use of channels to put substances into the filtrate that have not yet been eliminated or not enough has been eliminated from the blood this is how acid-base is balanced because we can remove hydrogen ion this is how potassium is balanced because we can secrete potassium ions and we can also remove certain toxins and other organic ions through specific transporters so go back to our initial summaries secretion and the proximal convoluted tubule is primarily going to be acid and other ions there is no effective hormones but there is a sodium potassium pump in the proximal convoluted tubules in the loop of Henle secretion can be sodium and chloride and that helps to maintain the osmotic gradient but there is no effect of hormones and there is still a sodium potassium pump in the loop of Henle in the distal convoluted tubules secretion of acid can occur and secretion of potassium can occur it is controlled by all of those hormone processes we just talked about secretion and excretion of sodium will be regulated by aldosterone reabsorption and secretion of water will be regulated by ADH and sodium regulation will be a sodium regulation will be opposed by A&P and BNP and again we always have the sodium potassium pumps so let's look at acid secretion acid secretion is regulated in order to maintain acid-base balance so normally this will cause urine to be slightly acidic as we're removing acid due to metabolic wastes and and other wastes in the body so the urine pH is normally a little bit more acidic than the blood a pH of about 6 and this will primarily occur in the proximal convoluted tubules distal convoluted tubule and collecting duct this is because we have hydrogen ion pumps and hydrogen potassium pumps and sodium hydrogen code transporters within these tubules this will be balanced ultimately with bicarbonate reabsorption the complexities of this process could take us an entire lecture but I'm going to leave it here for now in that we can secrete acid if we need to if acid is too high in the blood and that acid secretion can be balanced by conserving bicarbonate in the blood or excreting bicarbonate in the blood along side of the acid secretion and excretion secretion can also occur for potassium potassium is tightly regulated to maintain electrical gradients remember that we want low potassium in the extracellular fluid this is especially important for the heart and to maintain sodium potassium pump activity secretion will occur in the distal convoluted tubules and the collecting duct it will partly be because of the sodium potassium pump moving potassium into the tubules so you'll have high potassium in the tubular cell because of the sodium potassium pump and then you'll have a high to low gradient causing potassium to move from the inside of the cell into the filtrate where will be excreted in the urine you will then also have potassium channels to allow the potassium to pass through and enter the lumen that secretion will be stimulated by aldosterone and it will balance the sodium reabsorption that is also stimulated by aldosterone there's just a zoom in of that picture where you have high potassium inside the cells because of the sodium potassium pump and then you have a potassium channel which allows the potassium to follow its gradient and be secreted into the filtrate where it will be excreted out of the urine so here is just a reminder of aldosterone I'll let you guys review this later and the last piece is that we can also secrete organic ions this can include hormones foreign compounds pesticides pollutants food additives medications this becomes important when you look at the pharmacology of certain medications and how much they will be removed from the blood by the kidneys it affects the dosing of many medications and there are two types of carriers they are not selective so they generally will take an ions of any organic class of molecules or they will take cations of a general organic class of molecules what this means is that organic ions with negative charge will compete for carriers and organic ions of positive charge will compete for carriers this is where you can get drugs competing during elimination and that can cause drug interaction so two drugs that use the same carriers will reach their T max sooner if they are given together so if you have one medication that would normally be eliminated at a certain rate and then another medication that comes in and fills up its channels for elimination that can cause that other medication to be much higher in the body so you have to have dose adjustments for certain compounds especially medications that use the same carriers as other medications so there are several summaries in your textbook I suggest that you redraw the nephron and go through point by point where everything is occurring and I'll leave you with this the total plasma clearance of any given molecule is going to be a balance between the filtration rate and the reabsorption rate the net excretion of urine will be about one milliliter per minute so urine is produced at a rate of one milliliter permanent so substances can be excreted out of the plasma at a rate of one mil per minute this is plasma clearance the rate for any given substance will depend on how well it can be filtered how big it is how well it can be reabsorbed how many channels are present and how much will be secreted how many channels will be present in the opposite direction to get it rid of it in the in the filtrate so some examples creatinine filtered through the glomerulus but it is not reabsorbed there are no channels to reabsorb it and is not secreted so it's rate of clearance is exactly equal to its filtration and can be used as a measure for GFR clinically glucose will be filtered and a hundred percent reabsorbed at normal levels its rate of clearance will be much less than GFR zero there will be no glucose in the urine in normal condition so it has a zero clearance rate acid on the other hand will be filtered but it will be actively secreted so it's rate of clearance will be much higher than GFR because it is actively added in addition to what is filtered a lot will be added to the urine so once urine is produced it needs to be removed so we have stretch receptors in the bladder wall that will sense about 250 to 400 milliliters of volume and send signals through the parasympathetic nervous system to stimulate bladder contraction and open the internal urethral sphincter the external urethral sphincter is a voluntary skeletal muscle and can override that if the time is not convenient for the urine to exit so the bladder will fill as a process of urine being produced in the kidneys stretch receptors will activate parasympathetic neurons that will cause the bladder to contract and empty if the time is right the internal urethral sphincter will open along with the external urethral sphincter will allow that to stay open and urination will occur if not the external urethral sphincter will close around the internal urethral sphincter and we can hold it until later all right you guys have been holed it for a long time this was a long lecture thank you for your patience please let me know if you have any questions

Channel: Physiology for Students

Views: 89,465

Keywords: anatomy, physiology, urinary system

Id: 5VMTJCqlyLo

Length: 90min 21sec (5421 seconds)

Published: Sat Jul 23 2016