Renin Angiotensin Aldosterone System - RAAS

today we are going to talk about the iranian angiotensin aldosterone excess or the system right it is one of the very important physiological system which is doing lot of function but most important function is blood pressure regulation there how this is regulates your blood pressure so let's start first to understand its physiology right and to understand its physiology let's take an example that due to some reason if my blood pressure is going down for example I develop some hemorrhage or bleeding I'm losing the blood out of my body then how this system is activated because the duty of the system is duty of renin-angiotensin-aldosterone system is to maintain my blood volume and to maintain my blood pressure volume and pressure the vascular system should be regulated by this system it plays one of the very important role let's disturb the volume and pressure and see what happens to the system example we take that there is a patient and he got in roadside accident and he is losing blood right of course now we'll discuss that how the system is activated let's suppose that this is the circulatory system of that patient right the organs which are going to play a role in this whole game is number one central nervous system which is responsible for sympathetic outflow we will talk about the kidney this is their right rather trying the full kidney will draw a nephron here right so I draw a small kidney here right then there is a role played by the liver we'll talk about that what is that rule and then very important role is played by pulmonary circulatory system and of course we will not forget the role which is played by adrenal cortex now let's start one by one what really happens that when your patient is bleeding let's post patient is losing the blood here naturally blood pressure is going down and blood volume is going down is the right many things will happen in the body one of the thing which will happen that if patient is bleeding and blood pressure goes down the blood flow to kidney will increase or decrease decrease the first thing we'll say this reduced renal perfusion now whenever there is reduced renal perfusion right then means from the kidney the waves from the kidney start bringing and enzyme in the blood this enzyme is relays in blood from the kidney this enzyme is called renin what I have said that whenever blood pressure goes down kidney start producing more renin and more red income into blood but first of all we must study that you need thoroughly that by reducing the blood pressure how kidney start producing renin right for this purpose I will bring one nephron out and shown the nephron the operators which is supposed to release renin one kidney is how many nephrons you know kidney the very specialized tube you are millionaire as far as nephrons are concerned and one kidney there about 1.2 million inter farms but i will just bring out of this kidney one nephron out right let's suppose this is the nephron here and this nephron i am going to draw outside to explain that how really this system work this is one epithelial tube or nephron from the kidney right and we'll see how normally this nephron works and relationship to blood supply let's first this is afferent arteriole which is bringing the blood to the nephron these are glomerular capillaries and here is different arteriole what is this this is efferent arteriole here it is afferent arteriole right and here is your nephron now what really happens that we say that blood is patient is bleeding naturally blood coming to kidney is less so of course blood flow to this nephron is also less so afferent arteriole as poor blood flow now this very interesting thing nature has poor poor blood pressure measuring devices with every nephron what a master system in the nature that nature has put blood pressure measuring device with every nephron so that every never knows how much blood is coming to it is it enough or not so strategy will tell me what is the blood pressure measuring device with every nephron anyone has idea about you have any idea every nephron has blood pressure measuring device if you have 2.5 million nephrons right now in your to greatness there are 2.5 million blood pressure measuring devices with every nephron let me tell you month you see what is this this was afferent arteriole the smooth person these are the normal smooth muscles are afferent arteriole as afferent arteriole approaches ah what is this glomerulus right it's smooth muscles become altered there are no more normal smooth muscles these are very specialized smooth muscles right and this group of very specialized smooth muscle which are present in the wall of afferent nephron sorry efferent arteriole this is blood pressure measuring device these are the baroreceptors it means nature consider blood flow to nephron extremely important that is by nature my array my as the blood flow to every nephron right and this whole group it has been given a special name the name is called polka chien-po Kison so what is polka same polecats in our motive made of a special operators which is made of what modified afferent arteriole ur smooth muscle which are able to measure the blood flow to nephron and whenever blood flow to nephron become less whenever the blood flow to nephron become less they start releasing renin into blood so it means their double action one action is to measure the blood flow and second action is to release the renin it means they are acting like an endocrine gland because one group of cell releases the hormone into blood and acting into some distant area so every nephron a small endocrine system with it am i clear this is the blood pressure measuring device whenever your blood flow is coming less and there is less pressure on this operators as soon as this operators sense that blood flow is less or blood pressure is less it will start releasing which substance renin okay write it like this it is the red end so this is one way how renin is released by the special operators from that nephron now another mechanism is also their first understand normal normally what happened that when blood is moving through the glomerular capillaries there is some filtration done there is glomerular filtrate am i clear now this cruel murderer filtrate normally has lot of sodium and many other substances of course what are these these are the cells in the walls of nephron right now listen nephron has lot of cells in its wall now you see normally when there is normal blood flow then there is normal filtration and filtration normally is about 120 ml per minute in that all nephron this filtered material start going down but because it has lot of sodium nephron cells take the sodium back to the body this is right about 70 percent of the sodium of 60 to 70 percent of the sodium which is filtered as it is moving through proximal convoluted tubule it is reabsorbed back to the body we don't want to lose the sodium then sodium's keeps on moving forward and about 25 percent of the sodium is reabsorbed here if 65 percent sodium if 100 unit of sodium go down 65 is reabsorbed here and 25 is ribs out here how much is left I think your match is not of this 65 plus 15 25 65 plus 25 how much it become 90 it means normally out of the filtered sodium about 10 percent sodium will comes here or disband this is the end or this is the beginning of distal convoluted tubule and end of the thick part of ascending limb of loop of Henle here Nature has put a very beautiful system there are some cells here which are very very slightly modified structure this group of cells here the nephron cell that somewhat modified these are tall these are dark looking and these cells loved to paste the fluid here these cells are sensitive to they are sensitive to sodium they are sodium sensors what are what is the function of these cells these are sodium sensing cells right now actually these are pressure sensing system and this is sodium sensing system or this system together make a hole operators now look afferent arteriole with polka scene and this specialized group of cells from distal convoluted tubules and its junction with the proximal part so they write this group of cell and this group of cell they make one specialized operators these acting as a barrel receptors and these acting other chemo receptors these are the baroreceptors these are the chemoreceptor they measure the blood pressure they are the sodium concentration this is the right and they are held together by some connective tissue cells they are held together by some yes connective tissue cells now I told you this blood pressure measuring device baroreceptor group it is called paul kasin and this sodium sensing device which is present in every nephron it has a special name you know what is the name of this special group of cells which me or the sodium thank god the researcher who found it you did not put his name on this actually in the beginning when researchers looked at the nephron structure they found this area was a little bit more dark as compared to the rest of the nephron these group of cells are more dark so they just call it macula densa that there is some macule macula mean patch patch of cell which is looking very dense so this is called what is the name of this thin macula densa now pole kissing is from afferent arteriole Nakula 10 sites from distal convoluted tubule this is vascular component this is nephron component this is pressure measuring device this is sodium measuring device and they are held together through connective tissue cells which are called less s7 all this operators as a group all this operators as a group this present in every nefra it means every nephron has blood pressure measuring device as well as sodium measuring system and as a group paul kasin plus macula densa they have given a very special name to this and all of you know that name what is the name of this operators what's the name of this operator yeah juxtaglomerular operators have you heard of it so this is juxta glomerular operators yes they call it a special operators right just opposed to Cola Burley's juxtaglomerular with the glomerulus there is a very special operator thank God that we did not put a very complex name for it they just say they're special operators they never knew in the beginning what are its function now they know now let's go back to our analogy we were saying that person is bleeding blood pressure is going down blood flow is going yes down so when blood flow is less better receptors are activated in juxtaglomerular operators and the release renin meanwhile when your blood flow is less than glue below filtrations more or less less of course if there's less blood coming right then filtration is also less now you think really with your own cortex that if filtration is very less the Sun listen if filtration is very less the fluid will move through this lumen rapidly or slowly sure so whenever GFR is less luminal flow becomes slow when movement of a fluid through the lumen becomes slow then what happened these cells which are working on this luminal fluid they have more chance to work or less transfer more my friend of course look if there are many mangos going here attention this or that let's suppose there is water going a lot of mangoes going here and you are sitting here to catch the mangoes if flow is very fast you will miss the mangoes but if it is very very slowly coming you will catch every mango you get disease cells work like you they are not catching mangoes they are they're catching sodium there so when blood pressure become less we were a filtrate become less luminal flow become less these cell expect extraordinary amount of sodium and by the time the fluid little fluid reaches here it is more than normal amount of sodium or less than normal about the sodium less than normal amount of sodium then macula densa it love to taste sodium so whenever GFR is less than proximal part of the nephron work on the slowly moving fluid extract too much sodium so less sodium reach to the sodium sensing device and whenever macula densa feel there's less sodium comment it becomes super active it is activated when there is less rhodium reaching here and it releases some nitric oxide is released by it and prostaglandins are released by it and they activate these polkas in cells macula densa request this that please listen to us there is very little sodium coming here there is something wrong with GFR probably blood is not coming well so please release more renin so renin release become further augmented so now renin has been released under two influences under pressure change and under sodium change so every guru Marella's has just up our operators operators consist of blood pressure measuring device and operators consists of sodium sensing device blood pressure measuring device is derived from the afferent arteriole smooth muscle sodium medium device is a derivative of nephron cells together they make juxtaglomerular apparatus whenever blood flow is less to the kidney right this operators religious excessive renin and the blood now what this rendon should do renin should correct the balance bring the patient out of tragedy what was the tragedy blood pressure was going down and blood volume was going down now function of renin is to bring the blood pressure back as well as blood volume up so that patient does not die for example patient has lost one litre of blood then somehow blood pressure should be maintained and somehow blood volume should be maintained we will talk about how then it does it but before that we will talk about one more factor what is that that is that whenever your blood pressure go down whenever your blood pressure goes down let's suppose here is your heart so what really happens what is it what is this carotids system has carotid body what is the function of sorry carotid sinus not throated body this is this is what I'm saying this carotid sinus carotid sinus is an other blood pressure measuring device it also has baroreceptor when patient is bleeding the blood flow to here will be more or less less so whenever blood flow become less this carotid system is also activated and to special neurons the report to the central nervous system their blood pressure is falling they report to the central of a system that blood pressure is falling in the central of a system right okay let's forget about this part of the diagram and concentrate only on this this is going into peritubular capillaries and then it collect back as Venus and okay connected here this was the renal arterial flow and this is the renal venous flow venous blood going back right and arterial blood let us come back I was saying as soon as blood pressure goes down carotid sinus through the sinus nerves right this is through the vagus we get a nice enough glossopharyngeal nerve right this is message is given to the central of the system that blood pressure is going down as soon as central nervous system senses that blood pressure is going down it will stimulate the sympathetic outflow through vasomotor center in the medulla so from them adalah fibers will come down neuronal connections will come down and stimulate what sing out stimulate sympathetic outflow this sympathetic outflow which is going out suppose these are pre ganglionic sympathetic neurons and here are postganglionic sympathetic neurons I will not go to detail of all sympathetic fibers right now we are concerned only with those sympathetic fibers which are coming to juxtaglomerular operators these are sympathetic neurons which are coming to juxtaglomerular apparatus actually as soon as blood pressure start going down via the motor centers stimulated lot of sympathetic outflow come some of the sympathetic fibre come to just a glimmer or apparatus and what they will release there they will release neurons will release neurons release norepinephrine all right and these cells have receptor for norepinephrine these are beta-1 adrenergic receptor what are these receptors beta-1 adrenergic receptor you must know there are beta-1 adrenergic receptor present on just a glimmer operators because beta blocker blocked them also and help us in hypertension management so the beta-1 adrenergic receptors present over here so sympathetic outflow stimulate these beta 1 receptors and when beta 1 receptors are stimulated here more release of renin according to mr. Haddad speculations more release of renin so how many mechanism are there to release the renin from here number one to local and one systemic internal mechanism is low blood pressure in the afferent arteriole and low sodium concentration to the macula densa both of them release renin these two are internal mechanism of release of any extra renal mechanism of release of renin is most important sympathetic fibers connected with that is that right so we see this gesture glimmer of craters can measure the pressure directly can mirror the sodium concentration directly and in every emergency whenever sympathetic nervous system will fire rain and welcome now what this Renan will do let's see what this Renan is going to do this Renan is going to the general circulation from the Renan will go to the general circulation now Rendon has come to the judge systemic circulation right through the renal vein what Rendon will do here I told you Renan is an enzyme right and every of them work on special type of substrate it will also work on some special type of substrate before we go for that your liver has lot of hepatocytes hepatocytes produce lot of protein normally you know the producer humans and global ends alpha-globulin VTR global ends but not gamma globulin because gamma globulins are immunoglobulins antibodies which come from plasma cells these cells but most of the proteins other than the gamma globulins most not all but most of the proteins are produced by liver cells liver cell produced a one very special type of protein normally and this protein is called in geo 10 C no gen injured and sahaja right in Jotun see no Jen okay I will write it in small way this is injured tension or Jen right from where it is coming it is coming from liver and it is not coming only during crisis it is produced by the liver all the time right now all of you have in your blood in Jordan's Energon but as soon as the whren income it will work on the injured in solution it will work on injured in cinah Jen and convert the injured in solution into angel tenzen one it is injured ensign one so what is the function of Renan Rendon is an enzyme which can convert into attention to Jane into injured ensign one this is it right now all of you know it that when injured ensign one passes through the lungs it convert into angiotensin 2 that is the cross of understanding that in Jotun sin 1 when it is passing through the lungs it converted to angiotensin 2 it means in the lungs should be some enzyme which convert angiotensin 1 into injured ensign 2 and that enzyme is called angiotensin converting enzyme again an injured ensign one passes through the lung that converted to angiotensin 2 injure Henson to write when injured ensign passes for the lungs it convert into angiotensin 2 this is large protein molecule it is dead deca peptide I mean 10 amino acid then there is enzyme in the lung which break down two more amino acid and this product is octapeptide only eight amino acids I want to move on that angiotensin converting enzyme on which so many drugs work NGO tension converting enzyme a present in which part of the lung are the president bronchioles are the present in al July are the present in capillaries are the present where they are in the lung Ange attention converting enzyme is present all of you know the many drugs which inhibit that enzyme we must know where is that enzyme yes we talked to a bus no idea Jaime same yes hidayatullah you are the majority or you will try to guess something in the lungs everyone has heard there is a cons I'm called angiotensin converting enzyme have you heard of it or not masha'allah you have heard of it where is literally it is present no idea no idea Jamie just guess it wild guess you don't want even guess maybe it is present on the pleura yes any boiled gas all of your eye what do you think NUMA sites okay write it down on the book and put a very big cross on this you know why if it is present in all you lie then tell me one thing it means your blood has to pass through all villi I will I a blood flow system or air flow system the air pockets of blood fine yes [Music] now there are alveoli are air pockets and pulmonary capillaries are attached with them but pas Luna capillaries are not organized themselves right so one thing is sure Alvin I should not have the enzyme otherwise there will be tragedy blood has to jump into al July so that injured ants and one should convert into injured hands into okay let me explain actually the here is all villi let's suppose this airway and give that suppose on Buehler system this is the air pockets of course blood should not enter there is it right actually you know on the endothelial cells what are these endothelial cells or pulmonary capillary beds on the endothelial cells there is a region unique enzyme expressed this enzyme is expressed on the surface of endothelial cells that is why this enzyme is called acto enzyme because this is not intracellular online the cell is expressed from the surface of endothelial cells right not release into blood but now they believe that not only pulmonary blood capillaries have capacity to convert angiotensin one into two even some other capability beds can also do this function but for your levels you just remember that in the pulmonary capillary endothelial lining they are expressing on xym called what is the name of these enzymes you know they are very angry because you do not remember where they are you look at their expression right these are which enzymes NGO tents and converting enzyme what they are doing actually they are responsible to convert injure turns in one into angiotensin 2 this is a function of these enzymes these are the function of these enzymes which are called angiotensin converting enzyme x' that they convert injured ensign one and two injured ensign two and when we talk about the drugs like captopril enalapril assign apparel or other NGO Tencent converting enzyme inhibitors those drugs basically bind with these proteins and block their function when we say there are whole group of drugs called angiotensin converting enzyme inhibitor what is the function of those drugs these rails are basically bind with these enzymes and blocking direction every doctor knows that these enzymes are converting injections and one into injured ensign - but some good doctors know to do also one more function what is the second function of this enzymes there is another product in the blood which is called Brady kind in there is another product in the blood which is called Brady kind in bradykinin is broken down by these enzymes Brady kind in general look at it because it is inactivated Brady Kynan inactivation in activation bradykinin is visible later and enjoy dancing to is visa constructor so what is the function of this enzyme these on zaimes break down the wizard elated and produce with a constructor of course when blood blood vessels will constrict blood pressure will go up am i clear now so again let's recap up to this patient was actively bleeding right you could take some time renal perfusion is reduced then injured your what is this blood pressure sensitive cells release renin plus macula densa senses low sodium coming here a sign of low GFR that also forces the cell to release renin more our following blood pressure activate the sympathetic outflow and simple fibers coming to the juxtaglomerular ATIS further release of renin this Renan is an enzyme which come into general circulation and break down the angiotensin hojin into angiotensin one and when inductance and one is passing through the mainly when it is passing through the pulmonary circulation then enjoy tension converting ons ions which are normally expressed on the endothelial cell the pulmonary circulation they convert angiotensin one into injections into so they produce very powerful visual constructor and of course these enzyme the very active very intelligent while they are producing whether constructor that do not forget to inactivate the wizard a laters like bradykinin now we have the incidence into in our circulation now we have to see what is your transition to we will do in the body what is what it should do it should bring the bread freshen up and blood volume up that was the problem now so now we see how enjoy turns into is going to achieve its function let us come to the actions of NGO Tencent to first we'll talk about the classical action number one enjoy tensed into okay I will draw here circulatory system in a little detail the left heart and these are the arterioles from the aorta these are the arterioles and here is your right heart this is the venous system and of course in between these arteriovenous system there are what are these capillary beds we hope you must know that come from arterial side passes through the capillary beds and then it is drained to the venous side right this is right heart and that is left heart and of course you will not forget to draw that there must be long over there that this is your pulmonary circulation and blood gets oxygenated over there and then it comes to the left atrium and of course here is your what is this airspace is clear now we'll see first of all what is the action of angiotensin 2 on this system because pressure and volume is falling into the system first of all in certain sin to have the receptors on the arteriolar smooth muscle what are these arteriolar smooth muscle in Jordan sent to receptors are present on arteriolar smooth muscle plus Ange attention to receptors are also present on the vanilla smooth muscle so they are also present over here right now what really happens number one angiotensin 2 will work on what is this Venus smooth Posada then enjoy tension to act on the NGO tension to receptors on Venus smooth muscles veins constrict when veins will constrict can blood remain pool into n no most of our blood is accumulate present in the way in the veins contain about 70% of total blood volume that is why we call them the vascular component with the highest capacity or simply veins are called capacitance vessels so enjoy dancing to will construct the veins when winds are secreting pressure and veins will go up and blood will rush towards we're where the blood is going to the heart and then to the eventually left heart so under we know construction blood going to the left heart is less or more when you squeeze the Wain venous return to the heart is increased now listen when blood flow increases to the left heart it means RDF filling is more so venous return we know construction lead to increase venous return that lead to increase cardiac filling increase cardiac filling lead to increase and diastolic volume and increased and diastolic pressure at the end of the diastole volume and pressure is more in the ventricle so ventricle is stretched and according to friends Starling law more you stretch the ventricle more it contract frank-starling law is stated that within for the logical limit more you stretch the myocardial cell more they contract of course within physiological limit don't rupture them right now so whenever venous return is more and actually volume is more we say that pretty load on the heart is more and whenever preload on the heart is more preload is the amount of blood in the ventricle on which it has to produce contraction is it right so the whenever there is more blood accumulated here more it is stretch more it contract so stroke volume will become more so that will lead to increase stroke volume that will lead to increase stroke volume and of course when stroke volume is more than what is they are increase cardiac output and when there is increased cardiac output that will lead to increase in systolic blood pressure that was the point we wanted to reach you know were systolic blood pressure was falling as well as diastolic blood pressure was falling and your bleeding was going on for example bleeding was from here so blood pressure was falling so but we know constriction and increase in the venous return to the heart and increasing the end diastolic volume and of course increasing the contractility and increasing the stroke volume resulting in to increase cardiac output eventually increases systolic blood pressure because systolic blood pressure mainly depends on cardiac output am i clear during the systole blood pressure will go up meanwhile angiotensin ii will also work on what is this arteriole smooth muscle and arterioles will constant now if arterioles will become very narrow during the systole even lot of blood come here can it easily move to that side No so even if heart is not pumping because after the systole heart will undergo relaxation there will be unsettled Ashley during that Ashley of course your dick valve closes blood cannot go back the only choice for the blood during diastole was that no blood coming during the - Lee here but whatever blood is pumped here that should rush to the capillary side and venous side during the - way now if arterioles are open too much most of blood will run forward and pressure in the - Lee will fall but if our Tilda too narrow they are tight you think blood which is present during the - Lee here can it easily move so blood will be retained on the arterial side and pressure in the arterial tree during the dance Lee will be also increased and we say that diastolic blood pressure increase there is increase in diastolic blood pressure so that was our target what was the target then we were losing the blood systolic and diastolic blood pressures are going down by increasing the Vino constriction and venous return we increase the cardiac output in systolic blood pressure by increasing the arterial low constriction we reduce the movement of blood from arterial side to the venous side and blood which is trapped here even in during diastole it maintain the pressure on the right the story is not yet over meanwhile in detention - we'll also go to cells here and these cells in the outer what is this zona glomerulosa these are the cells and outer adrenal cortex the cells are called zona glomerulosa and what are the receptors here these cells also have receptors which are receptors for injured innocent to an NGO Tencent to work here what happens insurance and to work over here these cells start releasing a substance called Aldo stearin in geo tension - will act on zona glomerulosa and lead to the release of aldosterone what the hell does tear on will do this aldosterone now let's see how industry don't work okay I will draw just one cell here this is one cell Evan lied and this cell is called principal principal cell the P cells and last part of nephron jewelley they are in the second power half of the distal convoluted tubules and they present in collecting tubules what are these cells that's for sense actually this is let's pose the nucleus of principal cell it has different genes here of course every nucleus has genes now listen what L does foreign will do this elders Kiro on which is released by from where zona glomerulosa have to come into circulation through the circulation it will reach to the P cells and what it will do this aldosterone will come here let's suppose this is the eldest arrow when eldest children enter into the cell there it will find the receptors for eldest arrow and let's suppose this is the receptor for aldosterone so this is a very special type of protein which act like a key and this key is operated by which is which substance aldosterone this is aldosterone operated receptors what they do as soon as aldosterone bind this protein rush to the nucleus and open the locks of the genes what is do it is going to do open the locks of the genes when gene number one is opened by this aldosterone receptor complex gene number one start making a special type of protein and that protein is planted in the into basolateral membrane what is this these are the size and lateral side of which cells principal cells so these special proteins are planted into basolateral membrane under the direction of a low steer on what these proteins are doing are they doing anything important or just Paris facts fashion yeah what these proteins are doing these are sodium potassium ATPase --is they are present in every cell but in this kidney cell they are present on this electro membrane and not present on a luminal membrane but under the direction of aldosterone the concentration of sodium potassium ATPase --is on the basolateral membrane has been increased so what really happens that these cells use a sodium potassium pump so they keep on throwing the sodium from the cell to extracellular environment so cells start throwing the sodium from its cytoplasm to the blood and at the same time you must be knowing they are accumulating in the cell what is this Tashia these are sodium potassium pumps so it means under the influence of Elder steer on principal cell starts showing the sodium from their cytosol to the interstitium and start accumulating potassium so these cells become extremely poor in sodium and extremely rich in potassium under the directions of aldosterone mediated enhanced sodium potassium ATPase is then gene number two is also activated by the same gee number two is also activated by the same receptor system aldosterone receptor but second gene is stimulated this produces a product which will not go to the basolateral membrane which will product will come and it will be planted into what is this luminal membrane the special protein which is product of the second gene this protein fits into luminal side and what is this protein this is sodium channels these are not pump these are simply channels they let the sodium pass freely as sodium want to move now whatever little amount of sodium will come here if the cell is extremely poor in sodium sodium will rush in you know things move from high concentration to low concentration as soon as sodium come in through the pump it is thrown to the blood this is how sodium is reabsorbed under the direction of aldosterone that is you don't first enhances activity of the sodium potassium ATPase so that cells keep on pushing too much rhodium from the cell to the blood cells become extremely poor in sodium then sodium automatically starts shifting from the what is this nephron lumen to the cell and from the cell to the blood does it right so that sodium which was about to be lost into urine is reabsorbed and you know who loves to follow sodium who loves to follow sodium I think it's water right so naturally sodium is reabsorbed along with that water is also ray of the path and of course cell was rich in potassium so third gene is activated and third gene made potassium channels and potassium is more inside the cell or in the lumen inside the cell your hero's good so what will happen potassium will start leaking out so under the direction of what under the direction of aldosterone principle cells start reabsorb in sodium and water to the blood starts secreting the extra potassium into urine is that right now this salt and water this salt and water or you can say simply sodium and water which is retained in the blood they will decrease the blood volume or increase the blood volume so it is very easy if blood volume is increased if blood volume is increased then venous return the yes increase so cardiac ventricular fillings will increase ventricular contractility will increase and systolic blood pressure will go up this is how aldosterone the retaining salt and water take the systolic blood pressure up another sport to that eldest angiotensin ii has done this work through the elbow now angiotensin Deauville angiotensin ii will go to the central nervous system a change it's a long travel and it will work on the scepters present in the hypothalamus angiotensin ii will go and work with the receptors on hypothalamus and force some neurons in hypothalamus and they will activate action potential which will reach to the posterior pituitary and from there what will come out don't tell me and if anything what will come out from posterior children ADH don't tell me oxytocin that is not going to help the patient right now right so now in Geo turns into has made a long travel going to the hypothalamus stimulate which nucleus angiotensin ii ADH so propped you clear excellent so profit nucleus stimulated and eventually there is profit nucleus of the nerve endings and posterior which ovaries tittle and from there ADH come in to blood what ADH will do all no not going to detail just trust me I'm right what ADH will do it will make the last part of the nephron more permeable to water it will under the direction of ADH right the cells of last part of the nephron become more permeable to water this is a right and you know that last part of the nephron is going to metal off the kidney is that right and when this nephron is moving towards the middle medullary interstitium my delirium is hyperosmolar did you know that or not when I will teach you kidneys you will know that very clearly that middle interstitial is hyper or smaller a small allottee here is very high when this part of the nephron become water permeable here fluid is high both smaller here fluid is hyper smaller water will move from hypo smaller area it will be pulled to hyperosmolar area so water will rush from where yes from the last part of the nephron from the lemon water will rush through the cells to the interstitial so there will be increase water reabsorption so that water should not be lost into urine is there right and this water which is coming back it's too easy to understand this water will increase blood volume increase venous return of course increase cardiac filling increase contractility increase stroke volume increase cardiac output increase systolic blood pressure again we reach to the blood pressure it again reads the blood pressure is it right am i clear any other function of Co tension - extremely important function of angiotensin ii yet not mentioned is it is a super thermal letter of sympathetic nervous system this is a Supra stimulator of sympathetic nervous system so enjoy tension - receptors are present even lot of component of sympathetic nervous system so what really happens look here central sympathetic outflow will increase number one then these cells in the ganglia sympathetic ganglia they are also stimulated first central sympathetic outflow is stimulated then these ganglia are stimulated then if this is the postganglionic nerve and in let's pose this is the target tissue on which this nerve ending is ending this target tissue may be Venus smooth muscle this may be arteriolosclerosis or this target tissue may be myocardium normally what happened that postganglionic sympathetic nerve endings released nor epinephrine norepinephrine work on the receptors and once norepinephrine which is religion has done its action on the receptor it 80% of it is taken back by the nerve ending this is it right this is normal physiology now what angiotensin will do here angiotensin ii has a receptors here also it will stimulate the nerve ending in such a fashion the release of norepinephrine will be increased and reuptake or the norepinephrine will be reduced so amount of norepinephrine which is present in this area is reduced or increased if now ending is producing more epinephrine if now ending under the direction of injured nc2 is releasing more norepinephrine and not recapturing it then amount of norepinephrine present in the synapse is less or more it is more if you are releasing something more and not taking it back so that that thing will be there less or more you know it so in this way norepinephrine will be more in this area and even angiotensin ii has a receptors which increase its energy receptor concentration on the target tissue so it means what now angiotensin 2 is doing it is increasing the whole parameters of sympathetic nervous system increasing the sympathetic central sympathetic outflow increase increasing stimulation of sympathetic ganglion increased stimulation of sympathetic nerve ending increase responsiveness of target tissue LC what will happen with this look if sympathetic nervous system works more on the veins veins will constrict when they will constrict further more increase in venous return I know you must tell me more cardiac filling more contractility more cardiac output and more stroke valium sorry more increase in systolic blood pressure right this V no construction meanwhile when sympathetic activities increased on the arterioles more are durable construction and increase in diastolic blood pressure when sympathetic activity increase and releases more norepinephrine here more release of renin whole system is amplified this is the right and then we should not forget something very important angiotensin ii has receptors on the central thirst system so when intention to work on the those group of neurons which control the feeling of thirst patient who is bleeding he will feel thirsty of course you would ask water and if you have it he will take the water and try to increase blood volume again that is helpful but all these means what angiotensin ii i must say by all these means rainin angiotensin aldosterone excess what it is doing it is trying to elevate the blood volume and blood pressure this is the right i am i clear to everyone no problem this is for the logical functions of angiotensin ii and aldosterone but one most important pathological function I did not tell you there are some diseases in which blood flow to kidneys chronically low for example if you have congestive cardiac failure if you have a cardiac failure heart of a very poor out cathodic output for example I have very severe heart failure my systolic function of contact ility of the ventricle is very poor whatever the reason if my heart is a poor pump my blood flow to every organ is reduced including blood flow to kidney is reduced so all those patients in which heart feel as a pump cardiac output become less then blood flow even to the kidney is reduced and in these patients this qur'anic activation of renin-angiotensin-aldosterone axis you understand it in the same way who as person has cardiac failure of course is blood pressure also drops so sympathetic stimulation is also chronically activated so patient who have congestive cardiac failure right in them there's chronic sympathetic activation and this chronic renin-angiotensin-aldosterone activity when angiotensin ii level is chronically increased then something really very bad happen what happened if injured consent to is chronically increased and aldosterone is chronically increased this chronically increased angel tension - right and aldosterone will work on the myocardium and change the morphology of the heart this is something which is the recently discovered but very very important the patient with congestive cardiac failure have chronic elevation of angiotensin 2 and aldosterone and they chronically work on the myocardial cell and fibroblasts there this stimulates the proto-oncogenes genes which are concerned with growth these all myocardial cells start producing growth factors if myeloid cells start producing growth factor and these growth vector which are produced by the myocardium work on the myocardial cells so myocardial cells undergo hypertrophy but this is not normal hypertrophy it is pathological hypertrophy at the same time myocardial cells and fibroblasts start producing extra amount of connective tissue so myocardial cells become abnormal normally in light and in between the myocardial cell lot of hype erotic tissue and extracellular matrix is deposited and these things under cronic influences these things under cronic influences lead to our iteration in geometry of the heart chronically elevated aldosterone levels and chronically activated in geo tension to level in congestive cardiac failure lead to muffle logical changes in the heart what are these morphological changes myocardial cells undergo pathological hypertrophy and they undergo pathological production of excessive matrix and growth factors and many other alteration those alterations in the lump lump sum they are called cardiac remodeling so we can say that in congestive cardiac failure due to chronically which--it elevation of physio turns into and aldosterone myocardium undergo progressive that's a logical geometrical changes or we simply call it as dr. all said simply call it myocardium is undergoing remodeling phenomenon this chronic remodeling of myocardium makes a myocardial more poor contractile machinery and patient with congestive cardiac failure under the crouppen confluences of angiotensin ii and aldosterone go under progressive cardiac failure this is right in the same way chronically elevated angiotensin ii and aldosterone also work on the smooth muscles of vessels and bring pathological changes in them so this is one of the most modern concept that if you allow the renin-angiotensin-aldosterone access to work pathologically high that will eventually disturb the whole efficient geometry of the heart as well as vascular patches are produced this is the right that is why any patient with congestive heart failure at any stage it comes to you either at very early stage of late stage most important drug is drug which inhibit the NGO tension converting enzyme so that in geo tension too should not be produced and aldosterone should not be released or alternatively we use the drugs which block the receptors of angiotensin ii so that enjoy dancing to blocking the receptor blocking drugs are also very effective and not only they change the preload and afterload and blood volume but they also reduce the pathological progressive geometrical changes in the heart they prevent the cardiac remodeling we will discuss in detail what are these drugs and how the work the next session

Channel: Dr. Najeeb Lectures

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Rating: 4.882236 out of 5

Keywords: renin, angiotensin, aldosterone, raas system, renin angiotensin, renin angiotenin aldosterone, renin angiotensin aldosterone system, dr najeeb, dr najeeb lectures, Renin (Hormone), function of renin, aldosterone (chemical compound), Renin Inhibitor, nephron, RAAS, kidney, pressure, ace inhibitors, renin angiotensin system, hormone, urine, pathway, glomerulus, medical, angiotensin ii, angiotensin converting enzyme, armando hasudungan, vasopressin, nephrology, physiology, adh, blood pressure

Id: kDItNCpM7UI

Length: 59min 7sec (3547 seconds)

Published: Thu Jun 09 2016