in this video we will be looking at how uh the hormones actually allow us to concentrate the urine we'll be looking at aldosterone anti-diuretic hormone and the effects of atrial ntic peptide or atrial ntic hormone we'll also be looking at the reflexes which allow us to actually empty the urinary bladder and um look at some of the diseases of the urinary system so if we look at how we actually concentrate the urine and actually can change the volume of the urine which is actually lost and so um right we get the filtrate formation and that is pretty much constant right you know around 20 to 25% of the total cardiac output goes to the kidneys every day we're making 180 L worth of filtrate and we're pulling everything back that we need from that filtrate it's pretty much um you know that that's going to happen no matter what but we can regulate what's lost uh we can slightly change the volume of the urine being lost and that allows us to either dilute or concentrate the urine uh and uh we have to look at the reen and otens and aldosterone mechanism in the roles of anti-diabetic hormone and uh atrial natural itic peptide in fine-tuning the um contents in the volume of the urine so if we look at the reenan Angiotensin aldosterone mechanism and so first thing we need to know about this is this mechanism is kicked off due to low blood pressure and basically the purpose of the reion otens and aldosterone system is to counteract this drop in blood pressure to keep uh blood pressure within normal uh range and this is a control over blood pressure which happens basically not in the seconds to minutes sort of time range but hours today type of time range and so um the basics of this mechanism are rinin it's an enzy it gets released by ju to glomular cells those specialized cells of um the aphant tubu the apher arterial excuse me which are butting up against the juxtaglomerular apparatus as part of all this now rinin is released into the blood and it's a proteases and it's going to convert angiotensinogen a normally occurring plasma protein produced by the liver into Angiotensin one Angiotensin one will very quickly be converted into Angiotensin to this compound here by another protease Angiotensin converting enzyme sometimes referred to just as Ace now Angiotensin converting enzyme is found on the surface of endothelial cells those cells lining the blood vessels but it's especially found in the highest concentrations in the lung endothelial cells which kind of makes sense because if you want to convert a substance in the blood from one form into another the entire cardiac output goes to the lungs With Every Beat of the heart so let's just put that enzyme at very high concentrations in the pulmonary circulatory system we can find it in the on some systemic endothelial cells but it's much higher in concentration in the lung now um Angiotensin 2 is a Vaso constrictor so that's going to decrease the U diameter of arterials to increase blood pressure but it's also a big stimulus for aldosterone to be secreted now aldosterone is a hormone uh which uh will cause more sodium to be pulled back from the filtrate Angiotensin 2 will also make you thirsty therefore you'll drink more that fluid you're drinking will some of that will go and contribute to the blood volume that increas in blood volume will increase blood pressure and OT tensin 2 will also increase antidiuretic hormone secretion and we'll look directly at um what anti-diuretic hormone does in this video now basically aldosterone basically acts on the distal convoluted tubule in the collecting duct to increase sodium reabsorption and this hormone pulls more sodium from the filtrate this is how we can hormonally fine-tune the amount of sodium being lost in the filtrate and whe if we're pulling sodium back we're also going to be pulling water with it osmotically that water will contribute to blood volume that increase in blood volume due to that extra water being pulled from the filtrate will increase blood pressure so let's look at some of the details of aldosterone so we get a decrease in blood pressure that is basically sensed by the jux glomular cells they detect this reduced stretch on them and they secrete rein this enzyme right here rein will act on angiotensinogen now angiotensinogen is a plasma protein it's made by the liver it's always present in the blood just waiting to be turned into Angiotensin 1 Angiotensin one when it flows through the lungs will be converted to Angiotensin 2 by Angiotensin converting enzyme and that brings us to the next slide here Angiotensin converting enzyme as we mentioned is also a protease it takes Angiotensin one to Angiotensin 2 um so ensin 2 doesn't last all that long but ensin two will increase the rate of aldosterone secretion so we're going to get increases in aldosterone we're going to get thirsty we're going to be wanting salty foods and it's going to cause ADH secretion now the effect of ring and the effect of all those substances right all that we just mentioned right all those effects on thirst and salt and ADH secretion those are going to increase the blood pressure that's going to increase the stretch on the mular dens cells and reenan secretion will cease uh through all this and basically we're going to be looking at what aldosterone does um so if we look at what's happening here so we've got the filtrate down here we've got the apical membrane of the uh tubular cells we have the basil membrane of the cell right here and so basically this is the tubular cell from one side to the other and what we have here is we've got an aldosterone receptor we've got uh antiporters here we've got sodium potassium atpa and so um we've got the lumen of the tubule down here and aldosterone will come into the cell aldosterone is a steroid based hormone so it acts inside of the cell and it will bind to its aldosterone receptor and that's going to increase uh the number of uh antiporters and it will also increase the activity of the sodium pottassium atpa so that we move more sodium from the filtrate down here into the interstitial areas and so that's um how aldosterone works it's a um it just increases sodium reabsorption from the filtrate now when it does that um it's going to increase sodium potassium pump activity and sodium Transporters um now one of the effects of in increase in aldosterone secretion is that we're moving more sodium in this direction but that also causes pottassium to be secreted basically uh from the interstitial areas this way so sodium is here and potassium is moving this way and so under the effects of aldosterone we increased sodium reabsorption but we're losing potassium and actually very high potassium levels can actually also cause aldosterone to be secreted because now the kidneys are trying to get rid of that extra um potassium and that's totally fine that works because you know too much of anything's not good for you and so aldosterone is involved with sodium we increase aldosterone that leads to increase sodium moving from the filtrate into the blood blood and then that's going to increase blood pressure due to the increase in well blood volume all right that's aldosterone the next hormone we have to deal with also starts with the letter a and that's anti-diuretic hormone so this is a uh peptide-based hormone it's made by the hypothalamic uh the hypothalmic neurons themselves and it's actually released from the posterior pituitary and um it's released in response to an increase in osmotic pressure and so we have little uh osmo receptors in the hypothalamus and if there's an increase in the osmolality of the blood IE or the intertial fluid up there that means it's too concentrated that means um we want to stimulate ADH secretion because what uh ADH will do is to basically pull more water from the collecting duct that water is being pulled from the filtrate and being returned basically into the vascular system we have more fluid in the vascular system that will increase blood pressure but it will also decrease the osmolality of the blood a little bit because well we're putting more water in there and that will decrease the uh signal to these osmo receptors in the hypothalamus because we diluted that fluid out a little bit um we have bar receptors in the heart and in some blood vessels can they can also uh stimulate ADH release if there's a major drop in blood pressure which uh you know due to Hemorrhage or something like like that and so the way anti-diuretic hormone works is it affects the ability of the distal convoluted tubule in the collecting ducts to pass water and anti-diuretic hormone increases water reabsorption uh from the filtrate basically by causing aquaporins little membrane proteins which let water through uh they put more of these aquap porns into the membranes of the cells and um that movement of fluid from the filtrate into the interstitial area and then from there into the blood will increase blood volume and therefore blood pressure and we can actually have clinical situations where we're not making enough anti-diuretic hormone and that's actually known as diabetes insipidus it's another diabetic condition has nothing to do with blood glucose levels because when you look at the root of the word diabetes it just means a large urine volume diabetes meletus is that condition where we have a problem with u blood glucose control diabetes insipidus is a condition where we have um a large urine volume due to uh not enough anti-diuretic hormone and a poorly controlled diabetic will have lots of glucose in their urine that glucose will act as an osmotic agent and basically increase urinary volume and that's why diabetics have or poorly controlled diabetics I should say have a increase in uh urine volume so let's look at what happens in some detail of ADH on water movement through the uh collecting duct and so this can happen on the collecting duct cell or the distal tubule cells and so that's this whole cell here the filtrate is at the bottom and so we have one aquaporin here we've got the cytoplasm of the U tubular cell here we've got the other membrane the the basil membrane here of that tubular cell it's in contact with the interstitial fluid this blue area up here and we've got this nice peritubular capillary up here now we have the ADH receptor here it's a uh gpcr it's a uh G protein coupled receptor that's not all that important for our discussions today but when anti- dtic hormone binds to its receptor and there's another one of these complexes here we activate the the receptor which activates the G protein which activates adenin uh cyclas in this case we convert ATP into cyclicamp and that allows an aquaporin 2 containing vesicle to basically fuse with the plas with the plasma membranes on the apical surface of the cells and um so now that aquaporn 2 is going to let water into the cytoplasm of the cell and then another aquap porin which is always present on the basil membrane is going to let that water out now if this membrane vesicle which is not drawn to scale here I should point out doesn't fused with this membrane there's no aquaporn in this a in the apical membrane here water just bounces off that membrane and just keeps on going and stays in the filtrate down here but if we increase ADH that leads to an incre an increase in aquaporin we'll just abbreviate that as AP and that leads to increase water reabsorption that was painful so and we have to remember that this is a hormone it does its job we have to remember what a diuresis is a diuresis is just a condition where there's a lot of urine volume an antidiuretic condition is going to be one where there's not a lot of urine volume and an anti-diuretic hormone causes a state where there's not a large urine volume and we can do that by removing that water from the collecting duct if we pull it out of the collecting duct the urine is getting more concentrated and that fluid which is being removed from the filtrate goes into the blood increasing blood volume and therefore increasing blood pressure and so it's all due to controlling the amount of aquaporins in this U apical membrane of the distal collecting tubular cells and the cells of the collecting duct so more aquaporn too in those membranes more water leaves more water leaving the urine means that that urine is getting more and more concentrated and so this water is actually pulled out because of that very high concentration of solutes in the medulla this the water still needs well the aquaporn is the pathway for it but the force driving that fluid um from the filtrate into the interstitial areas is basically the osmotic pressure of that gradient running from 300 to 12200 in the medulla and remember the collecting duct will start up in the cortex and run down through the medulla and so if the antidiuretic hormone is there we have lots of aquaporins and the water can leave if there's no aquaporins well then no water leaves as we'll see so if we look at this diagram so we've got two different conditions here on the left we've got lots of ADH so lots of ADH lots of aquap porn and we can see that water is leaving this collecting duct as it runs through this osmotic gradient shown here on the right from 300 to 1200 that's the driving force to pull that water from that membrane and so as this filtrate goes down this way it's losing lots of water and it's becoming more and more concentrated until it becomes well the same concentration as the interstitial fluid of 1200 milliosmoles if we are really uh dehydrated that's as as concentrated as we can make urine because that's the maximum concentration of the interstitial fluid in our kidneys now if we look at the other situation here with no anti-diuretic hormone so the fluid in the distal convoluted tubul is at 100 milliosmoles now as this fluid runs through this collecting duct it's getting fluid from lots of different nephrons both cortical and um jomary but but that fluid stays at 100 Milli Osmos because there's no ADH present without that ADH we're not putting that aquaporin into that basil membrane that water can't leave the Lumen of that tubule it can't get into those cells to get pumped out into the interstitial area and so that water just stays there it's going to flow down into the urinary bladder and at that point uh once fluid is in the urinary bladder we can no longer change its concentration and again um we need this concentration gradient to uh pull that water out if we don't have that concentration gradient this area down here is going to be at 300 millios there's no reason for this uh fluid to come out the under those conditions the most concentrated urine we could make would be 300 milliosmoles and we would need lots and lots of um well water because we wouldn't be able to concentrate our urine anywhere past that and um so the other thing the kidney is constantly keeping and maintaining this gradient it's always there both counter current Loops excuse me are active all the time whether we need to use that loop at any point in time or not is it's not if we are um overly hydrated and need to dump extra water get rid of extra water and actually make a very dilute urine we still have this gradient intact we just don't put the aqua porins into the membrane and we allow all of that uh water to just pass through the system um we can actually get down to around 65 milliosmoles concentration in urine if we really are overhydrated um and that that's is due to extra pumping of ions by the uh distal tubule to um just dilute the urine as much as possible but you know we're making this gradient no matter how many liters of water a day that we are drinking which brings us to atrial ntic hormone this is the last of the hormones that we'll need to talk about it also starts with letter A so it's very easily confused with the actions of aldosterone and anti-diuretic hormone but atrial ntic hormone is unusual for a couple of uh reasons one it actually does not increase blood pressure it actually has the opposite effects and it will uh decrease blood pressure and it's also made directly by the heart we don't often think of the heart as a endocrine organ but um the atrial part in this hormone's name right comes from the Atria of the heart because that's where it it is made and it's actually made in the right atrium and that's because there are stretch receptors in these cells if there's an increase in Venus return or in blood pressure these cells are overly stretched which means they get signal to make atrial ntic uh peptide or atrial ntic hormone the natur uretic part of this is referring to sodium as we'll see because natrium in Latin is the word for sodium that's why sodium chemically is abbreviated na for natrium now atrial ntic hormone or peptide uh is um secreted when blood volume is high due to this extra stretching of the Atria and it overall has an effect of decreasing blood volume by basically uh inhibiting sodium reabsorption and by inhibiting sodium reabsorption we're leaving that sodium in the urine and we're not uh pulling any water back from that filtrate because we're leaving that sodium there that sodium is uh osmotically keeping that fluid in the filtrate itself we are also decreasing atrial ntic uh or and I'm sorry atrial ntic hormone will also inhibit ADH production so atrial ntic hormone the one which decreases blood pressure one of the ways it does that is by actively inhibiting the production of antidiuretic hormone so through all of this uh factors both of these factors it basically um causes more fluid to be lost in the the urine urine volume is increased that's at the expense of blood volume and therefore it brings blood pressure down and this decrease in blood pressure will uh decrease Venus return to the right atrium which uh reduces the stretch on those uh atrial cells and atrial ntic hormone production decreases due to that so regulation of blood pressure so again we're talking about what's happening here in the kidney that's going to be more of a long-term control of blood pressure rather than a a minute uh to Second type of control so you know we can do this by controlling ADH secretion and or atrial ntic hormone secretion um basically we can control blood volume to make sure that we can keep everything in place right so if we get an increase in uh blood volume we're going to kick off a bunch of different things which are going to kick in and so um we're going to increase ADH and aldosterone secretion well actually we're going to cause those guys to decrease which reduces water absorption uh and therefore that will bring blood volume down uh and so that's also that increase in blood pressure is also going to cause uh atrial ntic hormone to uh be secreted which uh increases urine production that increase in urine volume will decrease uh blood volume which decreases blood pressure the blood volume returns to normal and everything is okay and so uh you know everything is is good again so a couple of Concepts in um basically uh the physiology the the kidney itself as a more holistic look at it so plasma clearance is just how much well of a substance is removed from a volume of plasma in a given amount of time basically per minute and so we can uh calculate this using creatinine which is a normal breakdown product of muscle metabolism um but these substances have to be filtered they can't be reabsorbed they shouldn't be secreted back into the tubules and they can't be um metabolized or actually even made by the kidneys and this is a way we can use substances like this inulin is another one which has been used in the past to basically calculate the glomular filtration rate and so um glomular filtration rate is used as a measure of Kidney Health looking at um well decreases in GFR are an indication that there's uh kidney disease potentially occurring but these substances right so it's basically you know a substance which we can put into the blood or it's naturally produced by the body and put into the blood um we can look at the plasma level of the substance we can look at various time points and we can look at the urinary uh concentration of the substance at various time points and determine the GFR how much of the filtrate is actually being uh well actually how much of the blood is actually being filtered uh per minute and so um we can you know uh calculate renal plasma flow using substances like that par amino hipic acid which we is one of those substances which is um filtered earlier actually it's not it's filtered and uh and it's actually secreted into the tubul so this is a way to look at um the ability of the uh kidneys to actually secret materials uh and that uh third process of um urine formation and we can use this to basically determine uh which drugs or other substances are excreted by the kidney because if they sort of follow the same uh pattern of concentrations over time as the phah well then that's indicating that it's uh potentially being actively secreted by the kidney tubular cells now renal threshold is uh gets into this T-Max idea which we mentioned earlier right um the renal threshold for any substance and it will vary substance to substance is dependent upon the ability of the kidney to basically uh uh reabsorb that material from the filtrate um an example of that is glucose if glucose if plasma glucose levels are within a reasonable range um all the glucose will be totally removed from the urine and we won't lose any glucose in in the urine but we can see glucosa Uria which is the loss of glucose in the urine due to the fact that plus the uh glucose levels are so high that we are um reabsorbing as much glucose as we possibly can because every glucose uh transporter in the kidney tubules is working at 100% And if those uh kidney tubal cells are working at 100% to bring back all the glucose that they can we can still have a uh concentration of glucose in the plasma which is so high that even with those cells working 100% they can't reabsorb it all and therefore um we have surpassed the renal threshold for glucose that glucose is being lost in the urine uh and we can actually do this for a number of different substances which are actively reabsorbed which again gets us to this idea of Transport maximum it's the maximum rate at which a substance can be actively reabsorbed every substance which is reabsorbed has its own different uh TMax uh transport maximum um so if we look at what's happening here so this is the amount of glucose in the filtrate on the x axis the Y AIS is basically the amount of glucose in the urine and we can see that right around 375 migs uh per minute of um filtrate entering well that's the the glucose uh concentration right so if we're below that no glucose enters the urine if we're you know around that we'll get a little bit of UR glucose in the urine and if we're Above This level of glucose we're just going to be passing a lot of um glucose in the urine because the plasma concentration is well above the ability of the kidney to pull it all back um so in diabetes melus right the the amount that tubular load which is basically the plasma concentration of glucose exceeds the transport maximum and glucose is going to pop up in the urine um urine volume will increase because the uh filtrate has an excess of osmolality glucose is a uh osmotically active compound if we're keeping that extra where if we can't pull all that glucose back that glucose will exert osmotic effects and pull water towards it and that's going to increase urine volume when the blood glucose urine uh the blood glucose concentrations are very very high all right we now have to look at how the urine is actually removed from the body and so the uror are going to allow the transport of the urine formed by each kidney and trans and you know allow the delivery of that urine to the urinary bladder and at this point we are starting to see transitional epithelium that U that specialized type of epithelial cell which is only found in contact with urine urinary BL and the uh urethra will also be lined with this transitional epithelium now the urinary bladder it's a nice uh Hollow organ lined with lots of smooth muscle and it's also has this transitional epithelium and uh the muscle wall is part of the uh the trusser muscle which is uh basically involved in the uh urination process itself the trione is basically it's the small area on the inside of the bladder um it's basically between um where the two uror enter and the uh urethra allows the urine to flow out this sort of forms this little triangular area now this area basically expands less than the rest of the bladder when that bladder is filling up uh with urine over the you know uh over time now there's an internal um urinary sphincter which is in males and basically this is a little piece of elastic connective tissue and basically it uh prevents semen from entering the urinary bladder during the ejaculation process because we have to remember that the urethra inmes is also part of the reproductive system there's an external urinary sphincter this is skeletal muscle and it's basically surrounds the urethra as it extends through the pelvic floor basically this is a valve uh which will open and close to allow urine flow to occur or not now the male urethra basically goes from the inferior part of the urinary bladder and uh will go all the way through to the tip of the penis the female urethra is a much shorter u tube and it opens um basically just anterior to the um vagina so if we look at the the Anatomy here we see the two kidneys we can see one urer coming down from one kidney into the bladder the other one comes down here we can actually take a look at that uh here we've got this nice transitional epithelial cell tissue lining not only the ERS but the bladder and the urethra here um here we can see a drawing of the uh bladder wall with the smooth muscle uh there we've got rugi on the interior surface of the bladder to allow that bladder to expand we can actually see the trione area here right with the urethra um draining urine from this area here and the two URS coming into the posterior side of the bladder and on the lower portion of the slide we can see the differences in the uh well female on the left and the male uh urethra on the right female urethra is relatively short and just um you know exits outside the body wall uh the M urethra actually has to pass down through the prostate gland a gland of the reproductive system and then go all the way uh uh through the penis essentially so um how does urine actually flow through all of this and so it's basically that 10 mm of mercury of hydrostatic pressure which is forcing the fluid through the nefron itself once the urine exits the um kidney itself and gets into the uers peristalsis will actually move um the material down the uers and um basically that paracolic wave will start up in the renal pelvis and bring it down to the urinary bladder and that can be from uh one wave every couple of seconds to every 2 to three minutes um parasympathetic stimulation will increase the frequency of this peristaltic wave sympathetic stimulation will decrease it the um uers will uh enter the bladder uh through the trigone and they come in through the back side the posterior side and um fortunately pressure in the bladder basically helps compress the URS and prevents this urine from flowing backwards which will help keep any bacteria which are happen to be you know uh causing a UTI in the bladder itself to you know uh restrict them and not allow them access to the URS and the kidney itself uh sometimes that doesn't always work but it's nice to know that it's there so micro tincture basically the reflex which allows us to pass urine so urinary bladder its job is to hold urine it can hold about a liter uh and uh basically it can uh accommodate this due to the transitional epithelium stretching out and becoming much thinner and the stretch of the smooth muscle um will and the lack of a reflexive uh contraction of that smooth muscle allows that bladder to fill up and hold a very large volume of urine uh but this reflex can be uh activated when the urine gets stretched there are stretch receptors in the urin bladder to detect this um a parasympathetic action potentials will cause the muscles there to contract and U that will cause the urine uh to actually flow and uh decreas sematic motor signals actually cause the external urial uh sphincter to actually relax and again help with uh urine flow all right uh effects of aging on this system so as you get older the kidneys will actually decrease in size over time nephrons can be lost but amazingly we only need about a third of one kidney to maintain uh necessary uh kidney functions and uh full homeostasis um the amount of blood flowing through the kidneys will decrease with age glal numbers decrease the ability to to secrete and reabsorb decreases um due to these changes the uh ability to concentrate urine declines urine will be uh less resp or the not the urine the kidney becomes less responsive to ADH and aldosterone as we age um the kidney is involved in vitamin D synthesis and that U will also decrease with age which can contribute to uh calcium deficiencies and those calcium deficiencies May to osteoporosis and an increase in bone fractures if the kidneys get very compromised uh due to these age related changes a brief look at some of the diseases of the urinary system right we can have Glam nefritis this is a um inflammatory condition of the glomerulus itself it affects the um filtration membrane itself we can get plasma proteins and actually BL blood cells into the filtrate uh this is not a good thing this leads to increases in urine volumes uh and basically this is due to the osmotic pressure of these substances which are in the filtrate which really shouldn't be there uh we can have an acute glomular nefritis which is a often a response to a severe bacterial infection uh quite often due to a strep uh infection and um will uh generally take care of itself um but we can't have chronic glomular nefritis U the filtration membrane actually gets thicker and um basically eventually goes away the kidneys become nonfunctional at that point and you enter uh renal failure at that point pylon nephritis uh starts off also as a um bacterial infection but in this case it's probably most often an ecoli infection uh up in the renal pelvis which then spreads into the rest of the kidney um the infection destroys nephrons and causes all kinds of um reductions in the ability to basically concentrate the urine um if these conditions get bad enough we can enter renal failure we can actually have an acute renal failure um and this can happen quite quickly uh quite suddenly and um we can get uh a backup of waste products in the blood if um this failure is complete uh right you only will hang around for maybe one to two weeks if your kidney's totally shut down chronic renal failure is a more long-term condition the nephrons have been damaged for some uh reason and uh cannot maintain normal kidney functions this could be from chronic glamin nefritis uh trauma to the kidneys tumors kidney stones can also cause this again uh can lead to uh well the kidney's totally shutting down uh renal failure is often tracked by decreases in GFR GFR should be the glomular filtration rate should be around 120 uh 125 Ms per minute that will naturally decrease with aging just due to the decrease in nephrons and so you have to look at the age of the patient to deter whether you know a um GFR you know say 80 Ms per minute is you know a you know expected for this person's age or not and in acute renal failure lots of things can start to go wrong right we're throwing off all of the electrolyte balances we're throwing off blood pressure we're throwing off um blood volumes and so you know we can have uh problems in all of these areas