DIP Episode 430 - The Clutch Renin Angiotensin Aldosterone System Podcast (For Step 1-3)

All right welcome everyone my name is divine Welcome to another exciting episode of the divine intervention podcast and Into these podcasts I'm going to be addressing a very basic topic But a very high-yield topic to be completely honest with you I don't know I have not had a dedicated podcast on this particular topic for a long time So I'm going to remedy that situation or today So what's this riveting topic I want to talk about I want to talk about the Rinning and Jutenzen our Dosteron system the Rinning and Jutenzen our Dosteron system This is something that In some way shape or form you will see integrated Into any of the USMLE or complex exaps step one step two step three complex one two or three And even when you're going to clinical practice This is one of those mechanisms and pathways. That's really really helpful to understand You're just gonna see come up in many different ways is just one of those things you know Try as hard as you made a run away from it is always gonna keep waiting for you somewhere So it's just something you kind of want to know especially if you're going through like someone who can try no medicine It's probably a useful thing to understand. Okay, so What's the deal with the Rinning and Jutenzen system?

Well really what it does is it regulates a bunch of stuff It regulates blood volume regulates your vascular resistance regulates your in a sense Let me see a little bit indirectly regulates your cardiac output your blood pressures It just basically regulates a bunch of stuff right and if you look at the name of the system It cannot tell you the big players right says the Rinning and Jutenzen our Dosteron system Rin and Jutenzen our Dosteron system So the thing is there are three things there's Rinning which is important There is a Jutenzen which is important and there's our Dosteron which is important and the good thing I like about that order in terms of the names is it tells you which one triggers the other So the first problem the latter is going to be really and where those Rinning come from I mean we don't make Rinning out of thin air Rinning actually comes from the kidneys it comes from the kidneys it comes from your afrin arterio In fact, let's be a little more specific here comes from a subset of cells at the afrin arterio that are known as the Joc style glomerular cells the GG cells right and Rinning before we talk about its effects.

I think you'll be really helpful to Discuss some things that can cause you to release more Rinning like what in the world causes you to release more Rinning well One thing that can cause you to release more Rinning is if you're delivering less sodium to your distal tubules So the thing is if you think about it So I just said that the GG cells they are subset of cells of the afrin arterio The thing is those GG cells the line very close proximity to certain Cells that are a part of your distal convoluted tubule those cells are known as the macula densa The macula densa. So because they are known as the macula densa You know the sense sodium I think of them as like sodium sensors in a sense Right so they sense how much sodium is in the fluid that's coming through your kidneys and when they sense that oh There is very low sodium coming through the kidneys then that makes them think That's probably low blood pressure happening and if there's low blood pressure happening Then your body is like oh, we need to make more Rinning so you will tell the GG cells It will signal to them to go ahead and make more make more Rinning, okay It will signal to them to go ahead and make more Rinning and again You may be like divine. Why is it that less sodium coming to the macula densa tells us that the blood pressure is low? Well think about it.

Let's just work our way backwards If you have less sodium coming to the distal tubule That means not much fluid was filtered at the level of the glomerulus So you're like Why did I not have much fluid filter that the level of my glomerulus? Well surprise surprise it's because your glomerula capillary hydrostatic pressures are very low Okay, because think about it right if you have adequate glomerula capillary hydrostatic pressures You have extravacational fluid But if you don't have enough hydrostatic pressures in your glomerula capillaries That you will not have extravacational fluid into woman space. You will not for any good ultra-filtrate So what's gonna make you not have enough glomerula capillary hydrostatic pressure? Well surprise surprise if blood is not caught if there is not adequate amounts of blood coming into the afferent into the glomerula capillaries Right if there's not adequate amounts of blood coming into the glomerula capillaries Then you have enough hydrostatic pressure. So if there's not enough blood coming in that means that Adequate blood is not coming through the afferent material. That's what causes precisely what I've just described Okay, so that's why the macula densa when you see is that huh? Well, there's not much sodium coming through here It's almost like a surrogate. It's like a marker for decreased blood pressure So you want to see stimulate more reading release in those circumstances Now what else can cause you to make more reading?

Well, I'm not gonna cause you to make more reading is if you have beta-1 stimulation Right beta-1 is one of your energy receptors. I remember it's a G protein copul receptor. It's a stimulatory G protein copul receptor So it increases the activity of a denolate cyclase which converts ATP to cyclic AMP and in cyclic AMP Activates protein kinase A right but basically that beta-1 receptor if you activate it That's gonna cause you to release more reading. So obviously if you're taking a beta blocker What should a beta blocker do? Beta blockers should bring down your reading and if beta blockers bring down your reading You should have hypercalemia actually that's the mechanism behind beta blockers causing hypercalemia really as we go through the Podcast I'm gonna throw in a lot of very nice integrations that can really help you on in-sap So just kind of pay attention as we go Because again, remember if you make less reading you'll see why down the line you should have hypercalemia Or describe that later in this podcast and then and that thing that also causes you to secret more reading is if there's just low blood flow through your renal arteries, right? Just low blood flow through your renal arteries.

So let's say for example you have like fibromuscular dysplasia Which would be no younger person or you have renal arteries to noces or less you're like just systemically hypotensive All those things just gonna cause less blood to flow to your afternoon material If your afternoon material sees that man, an off blood is not flowing here Those GG cells are gonna freak out. They're gonna make a lot of reading and when you make a lot of reading You kick start the whole cascade, okay? You kick start the whole cascade So another way you can even think about this is if for example a person takes an insect what do you think an insect is gonna do to release? To your GG cells well theoretically although there there's a lot of varying mechanisms here So this is something that's really tested But theoretically if you took an insect an insect will inhibit cocks if inhibit cocks there will be less Prostaglandine production so instead of having dilation of your afternoon material You have constriction of your afternoon material if you constrict your afternoon material And there's not much blood is gonna be flowing through those GG cells They're gonna freak out and they're supposed to release Reading right they're supposed to it's not something that necessarily happens But is theoretically accurate to know that for for example is theoretically accurate to know that for for example So okay, so we've talked about the things that cause it to release reading so what in the world does running do?

Well reading does a few things the first thing it does is that or the major thing it does is that it's a Pre-eulitic enzyme it cleans something known as Angiotensinogen and geotensinogen it cleans it to form angiotensin one and then angiotensin one Goes to the pulmonary capillaries it goes to the pulmonary capillaries That's where you have Ace angiotensin convertin enzyme and you're tensing convertin enzyme We'll convert angiotensin one to angiotensin two right now one thing I just want to comment on is it's pretty high yield for the US Similarly exams to know that your pulmonary capillaries have very good metabolic activity at least in general There are two high yield metabolic activities. You need to know that occurring the pulmonary capillaries number one is Ace just literally doing his job converting angiotensin one to angiotensin two and number two is also knowing that the pulmonary capillaries Have the ability to break down serotonin. This is why people that have carstoid syndrome carstoid syndrome They don't have left-sided heart lesions. They only have right-sided heart lesions because when the serotonin from the carstoid Comes through the pulmonary capillaries.

They are metabolized the way right so that they do not affect the left side of the heart That's pretty important to know And one nice question that our friends at the MB is being as smart as they are can throw an exam You know step one or step two or step three probably say more so step one is they can give you a question Where you're supposed to delete Angiotensin one and angiotensin two concentrations between Blood sample drawn from the pulmonary artery versus a blood sample drawn from the pulmonary vein well think about it Obviously in the pulmonary artery the angiotensin one level should be high and the angiotensin two levels should be very low Why because it has not angiotensin one has not undergone metabolism yet and then in the pulmonary vein Your angiotensin one level should be very very low and your angiotensin two levels should be very very high Because now you're a distal to the pulmonary capillaries So because you are distal to the pulmonary capillaries you have converted your angiotensin one to angiotensin two Again, this sounds like a very benign very mundane concept But I promise you in the heat of an exam where you're sweating bullets You you would want to have this thing on your fingertips So it's not something that you have to keep thinking thinking thinking about it, right? So again after you after you know the pulmonary capillaries angiotensin one is converted to angiotensin two And in that angiotensin two does a bunch of stuff, right?

I mean like is this a pretty amazing compound the first thing it does is that it's a very powerful viso Constructor believe it or not angiotensin two is one of the most powerful viso constructors in the human body I'll say it again And you're tensing two is one of the most powerful viso constructors in the human body How in the world does he do that? Well, he does that by binding to the angiotensin two type one receptor So it's the type one receptor is the angiotensin two type one receptor. So by doing that it will bind to your It will bind to your it will bind to that receptor and it will cause a viso construction obviously if you viso Constrict that's gonna reduce your system that's gonna increase whoops That's gonna increase your systemic vascular resistance Obviously if you increase your systemic vascular resistance, your blood pressure is gonna go up Now he angiotensin two also especially in the earlier parts of the kidneys like the proximal tubule It actually stimulates the reabsorption of sodium So think about it if you stimulate sodium reabsorption Then you're gonna be stimulating the reabsorption of water Ultimately that's gonna cause fluid retention that's gonna cause an increase in blood volume Now a third thing that angiotensin two does is that it goes to the zona glomerulosa of the adrenal cortex I'll say that again It goes to the zona glomerulosa of the adrenal cortex What does it do in the zona glomerulosa?

Well, it stimulates the release of our dostero Right now dostero is a very powerful compound one of the things our dostero does is that it increases the activity of the Inek channel the sodium channel that we find at the principal cell of the collecting duct on the urine surface of the Collecting duct of the principal cell of the collecting duct So when you increase the activity of that channel you're gonna reabsorb sodium as sodium is being reabsorbed Water is gonna follow but it also causes you to excrete potassium into the urine, right? So our dostero makes your reabsorbed sodium and water and mix your excrete potassium and also our dostero And acts at the level of the alpha intercalated cells I'll say that again it acts at the level of the alpha intercalated cells What in the world does it do at the alpha intercalated cells? Will it cause you to secret protons into your urine? So whenever you have a high out of the stron state you're literally gonna be dumping protons in your urine You're literally gonna be dumping protons in your urine. You literally. I'll say that again gonna be dumping Protons in your urine if you don't put on in your urine you're gonna get a metabolic Alkalosis, right?

You're gonna get a metabolic alkalosis when you have a high out of the stron state So think about it if you're taking an out of the stron antagonist So something like Spurno-Lakhtun or a player in known it will then make sense that hmm This person is gonna be getting the opposite of what our dust run causes So the person is gonna get a hyperchylemia right because instead of getting rid of potassium in your urine You're holding them onto them, but you also have a metabolic acidosis, right? You'll have a metabolic acidosis because oh instead of getting rid of those protons from the level of the alpha intercalated cell Of the distal nephron the food on to those protons, right? That's a high pool out of your own state causing a metabolic acidosis to be honest with you That's actually a normal anion gap metabolic acidosis, right?

So whenever you have a low out of the stron state, it gives rise to a magma Actually, cause of RTA, let me get a little more specific because it's a Reynolds-Belacidosis More specifically, causes a Type 4 Reynolds-Belacidosis Let me tell you this, whenever you see a person that has an RTA and they have hyperchylemia With said RTA, that's a hypo-out of the stron state That's a Type 4 RTA, that's gonna hide you to know Really, I'm telling you if you pay attention to this podcast You will absolutely crush many questions on your exams And another job of our dust turn is that, I mean of Anjotensin II Is that it goes to the posterior pituitary It goes to the posterior pituitary and causes you to release ADHD anti-diarrytic hormone ADHD is also called visopressin, where we know that visopressin It acts on ADHD receptors, the visopressin receptors At the level of the principal cell of the collecting duct And that causes you to reabsorb a lot of fluid from your urine And also, visopressin, believe it or not, is also a visoconstrictor In fact, this is one of the reasons why it is used in people that have septic shock Although remember, if you have septic shock, you gotta start off with neuropinephrine first We usually try neuropinephrine as the first line visoconstrictor If neuropinephrine is not working, you can try it in Africa and try visopressin To help you visoconstrict and kind of help you out there And one of the things with angiotensin 2 is that it also causes you to have cardiac hypertrophy It causes cardiac remodeling So the thing is, you may be like, oh, divine, wow Hmm, that may point me out to something Well, what do you think I'm trying to point you out to here?

Well, think about it There's these pesky details about the drugs that are supposed to improve survival in CHF Things like your beta blockers, your industrial antagonists Your ACE inhibitors and ARBS Well, why do you think your ACE inhibitors and ARBS improves survival in heart failure? Hmm, well, maybe if you're shutting down cardiac remodeling Maybe if you're shutting down aborant hypertrophy, that may help your heart Right?

So those drugs are pretty good, good from that perspective So really, to be honest, if you understand all these things and mentioning Then you understand the reverse You'll understand certain markers you get When you take an ACE inhibitor and ARBS And before I delve into those, one thing I just want to say is If you like the way I explain things, you may be interested in the classes that I offer For the USML Es, I have a biostatistic bootcamp that's taking place next week Thursday On the 15th of December If you struggle biostatistics, as you can see from my podcast, I'm not big on Well, let me just give you the material to memorize Most USMLE questions these days for biostat are not memorization questions They are questions where you actually have to reason through bio stats In fact, sometimes, even if you know they're formula, you won't be able to answer the question correctly So if you want to become a biostatistics expert, I'll strongly recommend taking my biostatistics bootcamp on the 15th of December If you struggle with test-taking strategies, this is for anyone taking step one, step two or step three I have my MDME test-taking strategy scores, that's going to be taking place on Friday, the 16th of December Thousands of people have taken this class and they are found to be profoundly helpful And then if you're studying for step two or step three or complex level two or three Or you're taking your shelf exams and you want like a very good solid overview of most of the high-yield things you see on your shelf exams I'll encourage you to take my 20-hour course, it's going to be taking place from the 19th to the 22nd of December All these courses are going to be taking place through Zoom And then finally, if you're also, and again, these courses, especially the review course, is going to be based entirely on scenarios Less than 5% of it is a lecture, like 95% of it ar

e just straight-up scenarios Because again, your exam is not a bunch of lectures, your exam is going to be a bunch of clinical scenarios And you're going to see me integrate things across multiple disciplines to really help you understand the concepts And then for those that are taking step one or complex one, I have a review class taking place in January Starting on the 5th of January, it's going to be a 5-day class, 5 hours HD, 25 hours total And the class is a step one review, it's a very high-yield integrated step one review It's very ideal for people taking step one or step one or complex one Or if for example, you're a person that's taking complex two or complex three or step two or step three And you have a poor clinical science foundation To be honest with you, even if you don't have a poor clinical science foundation, you'll find the course to be profoundly helpful The course is going to integrate so many things in clinical medicine across so many disciplines By the time you're done with the course, you'll feel very comfortable You have a very solid, very excellent knowledge base So if you're interested in any of these classes, the all take place through Zoom Shoot me an email and I'll give you some more information that you can reserve a spot for yourself Okay, so I said I'm going to talk about the opposite of what happens when you take an ACE inhibitor and ARB If you take an ACE inhibitor and ARB, think about it I mean, they can give you questions on your exams We have to talk about the effects on preload, for example Think about it, what's not going to do to your preload?

Well, I just said that angiotensin 2 on its own and also throughout the stern makes your ribs absorb sodium and water in the nephron Well, if your ribs are in sodium and water, that's going to increase your blood volume So if you block those effects, you're going to actually decrease blood volume If you decrease blood volume, then you're going to decrease preload If you decrease preload, guess what? You're going to decrease cardiac output And also, if you think about it from the systemic vascular resistance perspective Well, guess what? If you're antagonizing the actions of angiotensin 2, you're going to bring down a person's systemic vascular resistance You're going to lower their blood pressures that way Okay, you're bringing down systemic vascular resistance, you're going to lower their blood pressures So if you really think about it, you're bringing down the systemic vascular resistance You're bringing down the dastolic blood pressure when you take an ACE inhibitor or an ARB And also, you're bringing down the systemic blood pressure because you're lowering cardiac output When you take an ACE inhibitor or an ARB So overall, what's the effect going to be on pulse pressure when you take an ACE inhibitor or an ARB?

Well, let me tell you a secret, it's going to reduce, it's going to decrease those stains Because think about it, you're causing very major drops, very, very major drops in systemic blood pressure Because your cardiac output is going down, because your preload is lower We're also causing very major drops in your dastolic blood pressure, you're causing major drops in your dastolic blood pressure So overall, the net effect, because I know some people may be like, wow, divine If you're only looking at it from the perspective of dastolic blood pressure going down, you'd be like, oh, the pulse pressure should increase But no, two things go down, dastolic blood pressure goes down, systolic blood pressure goes down The net effect is an overall decrease in pulse pressure And overall decrease in pulse pressure And remember, when you take these ACE inhibitors, especially maybe not so, in my lemme not say not AR Bs, but ACE inhibitors ACE inhibitors, what do you think they do to your levels of bradykining?

What you're going to raise your levels of bradykining, bradykining goes up You're going to get that pesky non-productive cough that we find with many ACE inhibitors Usually we don't get that problem with AR Bs, because AR Bs have nothing to do with ACE They literally have nothing to do with angiotensin-converting enzyme And I guess while we're on that topic with angiotensin-converting enzyme, remember, levels of ACE will be increased when you have like long problems Especially like sarcoidosis Because remember in sarcoid you have a lot of inflammation in the lungs, you have those nasty granulomas So you can make a ton of angiotensin-converting enzymes So ACE is actually pretty high in the bloodstream if you measure it in people that have a sarcoidosis Just going to figure that out as an extra point And then another thing I want to say is that, you know, to this renein angiotensin-adosterone system There is like a counter regulatory mechanism So if you actually look at the atrial of the heart, atrial of the heart, you make something called A&P Itrial-naturetic peptide The ventricles of the heart actually produce something known as B&P Brain-naturetic peptide, that term brain-naturetic peptide is a misnomer It does not come from the brain, it actually comes from the ventricle So B&P comes from the ventricles, A&P comes from the atrial And the thing is, in general, I know comment on A&P because that's the big, big one They love to go after an exam But A&P, I mean, it does a bunch of things that basically go counter toward the renein angiotensin-adosterone system does Right?

Like for example, A&P decreases the production of renein, it decreases renein production Well, if you decrease renein production, you're going to, again, pretty much offset its effects And the thing it also does is it inhibits the inect channel A&P inhibits the inect channel in the principal cell of the collecting dot If inhibits that inect channel, you're not going to reabsorbed sodium So you're going to be wasting sodium in your kidneys, you're going to be, water is going to follow That's going to reduce your blood volume, right? That's going to reduce your blood volume So again, A&P is, and also is a very powerful visual dialed leader And some of you may be like, I'm defying like, how do I wrap my head around this? How does A&P cause visual dilation? Well, here's the thing A&P when it acts on its receptors, the A&P receptor is a receptor that actually activates guanilit cyclists So because it activates guanilit cyclists, that's going to cause the conversion of GTP to cyclic G&P And then cyclic G&P is going to stimulate protein kinase G Protein kinase G, and you look at the name protein kinase, Geter kinase So that means it's forceful release things Well, one of the things that most of us for relate is myocene lys chain phosphatase Right?

So protein kinase G phosphorylates, myocene lys chain phosphatase When you phosphorylate myocene lys chain phosphatase, you're going to activate it Myocene lys chain phosphatase is activated when it is forceful related So again, when myocene lys chain phosphatase is forceful related, it becomes active Well, what does a phosphatase do when it's active? It's going to cleave off phosphate And what is it going to do? It's going to cleave off phosphate from the myocene lys chains When myocene lys chains are not forceful related, when the phosphate has been locked off of them Then you cannot combine with acting, you cannot interact with acting So you're not going to get any smooth muscle contraction, and the muscle is going to relax And if the muscle relaxes you, if you have smooth muscle relaxation, that's going to cause viso dilation That's going to cause viso dilation So it's pretty amazing from that perspective And the thing that really makes you release A&P is when your heart muscles stretch So when you have a stretch in the wall of your atrium, there are volume receptors in your atrium They say, man, this is not good.

We need to get rid of some of this blood volume And that's going to cause the trigger to release of A&P, and that's going to cause you to release all that extra volume And I guess one other thing I can say with this A&P B&P business There's an enzyme that happens to break them down There's an enzyme that happens to break them down A friend that the MBM is actually love this enzyme It's actually called an aprylicin For a lysine is an enzyme that breaks down A&P and B&P And I'm just talking about all these beneficial effects of A&P B&P How reduces blood volume, reduces blood pressure, causes visodilation I mean, it may be something that may be pretty helpful to a person that has CHF It kind of sounds logical Because the brain that has CHF, they have volume overload It's probably not a good thing for them to have all that extra volume Because that volume can end up in the lungs and kill them, which is not a good thing So one way you can temper those effects is you can give an aprylicin inhibitor In fact, an aprylicin inhibitor is a drug like Sacubitrial I'll spell that S-A-C-U-B-I-T-R-I-L Sacubitrial, many times actually you combine these drugs with an ARB Like Valsartan, like Valsartan, Sacubitrial You combine those two drugs to give them that actually improves survival in heart failure So Sacubitrial inhibits an aprylicin By inhibiting the aprylicin, you're going to decrease the breakdown of AMP and BMP So since you're decreasing the breakdown of AMP and BMP, you're going to get more of those beneficial AMP, BMP effects It's definitely pretty helpful in people that have heart failure Okay?

Pretty helpful in people that have heart failure Okay, so I think I'm going to go ahead and stop here Again, I hope you found this podcast to be really helpful I do offer tutoring for all the USMLE exams, step 1 to step 3 Complex level 1 to 3, I do not tutor to O-M-M I do not tutor to O-M-M And then I also have review courses as I've described already for step 1, for step 2, step 3, complex 1 to 3 MBME test-taking strategy courses, biostatistics courses If you're interested in that, I also offer help with ERAS applications and MOKIN reviews Again, I've worked with tons of people along those lines that I found it to be very, to be really, really helpful Really, really beneficial And then I have these podcasts on the major podcast apps, Apple Podcasts, Google Podcasts on Spotify I have a You Tube channel, Divine Intervention, USMLE Podcasts and Videos Divine Intervention, USMLE Podcasts and Videos I do upload videos on that You Tube channel, so please subscribe to that when you get there And I also upload versions of my podcasts as well on that on that You Tube channel So again, just subscribe there if you're a person that uses You Tube heavily You can get more productive studying out of your You Tube time by just hitting that up And then I have another website known as Divine Intervention, USMLE Podcasts and Videos Divine Intervention, USMLE Podcasts and Videos Divine Intervention, USMLE Podcasts and Videos Oh, sorry, whoops Misspoke there, whoops I have another website called Divine Intervention Lifelesses.com I kept repeating the name of the You Tube channel, my apologies there But Divine Intervention, Divine Intervention Lifelesses.com It's a website that I made because many people said, wow, Divine I really love the life lessons you put at the end of your podcast So I made a new website, Divine Intervention Lifelesses.com I post about two podcasts every week, about 10 to 20 min

utes long And I use the Bible to describe how to deal with a particular life problem I mean if you know I'm a Christian, so I made these podcasts and again Many people actually subscribe to that and if I need to be really helpful In fact, the podcast associated with that is also on Apple Podcasts It's called the Divine Intervention Lifelesses Podcast Now, real quick before I end today, I just want to talk about a quick life lesson And that's the importance of contentment, contentment, contentment, contentment The thing is, this is something that I know is pretty common in medicine Because medicine attracts a lot of type A personalities People that are very driven, people that are very ambitious And the thing is, there's nothing wrong with being driven, there's nothing wrong with being ambitious But it's also important to just recognize the importance of being content Because the thing is, when a person is super driven, when a person is super ambitious They are always striving for more, more, more, more, more, more, more, more, more, more The thing is, if you have this, always striving for more mindset You will never be satisfied with what you have And let me tell you this, whenever you're not satisfied in life You will pretty much never have peace, that is just the truth Because when you get something and it seems really good, it's going to be good to you for like a deal too But after that deal too, you're looking for the next thing that's going to drive you Right?

You see your scores, you're like, man, I've studied really hard for this USM exam I got a 260, you've studied for it for like one year, very driven everything, you've crushed it But then, after those USM elite scores come, they will go and you return back to your old state And then you're looking for the next big thing Right? And the thing is that behavior just kind of spreads to many other parts Ends of spreading inadvertently to many other parts of like the medical students' life Right? You just never content with anything, you're never content with anything So the thing I think I want to say to you here is, just ask yourself like what gives you joy in life It's just very important for you to kind of sit down and clarify What gives me joy? Is it my USM elite scores that give me joy? Is it my family that gives me joy? Is it money that gives me joy?

But I will encourage you, there are many things like money for example that does not give last-team joy USM elite scores, I promise you do not give last-team joy It doesn't matter how well you've done on the USM elite, I promise you after a few years If you're able to hold onto that joy for a few years, it's going to be, it's going to wear really quickly I can tell you that for sure, I'm not saying what I do not know So I'll just encourage you like make sure you focus on things that are more substantial As sources of your joy And really maybe one thing I will say is don't let your surroundings really dictate your joy Because if you let your surroundings dictate your joy Man you're going to be a very unhappy person, you're going to be a very unstable person Because basically your moods are going to yoyo you with the way your environments look like So if for example it's a wonderful job, everyone is treating you well, you're crushing everything You're going to feel good, but then if it's a very bad work, everything is going horribly And things are not going well, then you're going to feel horrible Or if people treat you well, treat you nicely, they hype you up, you feel good But if people treat you poorly, you get crushed, right?

That's one of the reasons why like the media, you shouldn't depend less on your star In some way shape or form, you shouldn't depend on the media to control your joy No, no, no, no, because the media they are your friends today So to be honest with you, I feel like the media is almost like bipolar sometimes You know, you kind of look at basketball for example You know, you have this player, this person is like scoring 30 points a game Absolutely crushing it, everyone in the media loves you, they're like wow, MVP candidate Wow, this person is top 5 in the NBA, wow, this person is generational talent But then when you have like a string of three or four bad games, they just absolutely just pillage on you Should this person be treated, or this person is the worst person in the world? Wow, this person that no, is this person worth their contract? Right? So that's the thing, like don't let external things control your joy Let your joy come from within, I mean like you know, as a Christian, there's this part of the Bible that says rejoice always Again, I see rejoice, so your joy should be a consistent thing for you Right?

But it will be consistent, your joy will be consistent if it's coming from the inside If it's not coming from a femoral things that can't lie on the outside So I'm not gonna rumble down for a bit, but again, I hope you find this life lessened to be helpful Because I'm telling you like when you are not content, it can really cause you to do some very nasty things in life I mean one of the reasons why people commit suicide is because they're just not content with life So again, I just encourage you like just develop that contentment Regardless of what is going on around you, just tell yourself that you know what is gonna be okay This too shall pass, just remain content, celebrate your victories And you know, if things are not working out the way you want them to work out You know, just trust that things will get better, but again, and also obviously change your strategy If you're doing things that are making things no work out well for you You should be doing those things that are making things no work out well for you That's just kind of common sense, right?

And I encourage you, what way you draw your joy from If you draw your joy from things that change like shifting shadows You're not gonna have long term peace But if you're drawing your joy from the inside, from things that have like lasting value You're very likely to be a little more stable in life So thank you for listening to me today I'll see you in the next podcast, have a wonderful rest of your day God bless you, bye for now, thank you

A subset of cells in the afferent arteriole called juxtaglomerular (JG) cells.

1) Low sodium delivery to the macula densa, and 2) Beta-1 receptor stimulation (e.g., sympathetic activation).

In the PA, Ang I should be high and Ang II low; in the PV, Ang I should be very low and Ang II should be very high because the lungs contain ACE (Angiotensin-Converting Enzyme).

It causes vasodilation, decreases renin production, and inhibits $\text{Na}^+$ reabsorption in the collecting duct.

They inhibit the breakdown of bradykinin, leading to its accumulation in the lungs.

ANP comes from the atria (stretched by atrial volume), while BNP comes from the ventricles (stretched by ventricular volume).

The macula densa.

The Angiotensin II Type 1 Receptor ($\text{AT}_1$R).

Aldosterone.

Hyperkalemia, Metabolic Acidosis, and hypoaldosteronism (or low aldosterone effect).

Sacubitril.

Stimulation of $\text{Na}^+$ reabsorption, leading to water retention and increased blood volume.

The macula densa.

The Angiotensin II Type 1 Receptor ($\text{AT}_1$R).

Aldosterone.

Hyperkalemia, Metabolic Acidosis, and hypoaldosteronism (or low aldosterone effect).

Sacubitril.

Stimulation of $\text{Na}^+$ reabsorption, leading to water retention and increased blood volume.