DIP Episode 146 - Comprehensive USMLE Renal Pharmacology Part 1

Okay, welcome. My name is Divine, I am a resident and this is episode 146 of the Divine Inconvention Podcast. And in this podcast I'll be talking about Renault Pharmacology, I'm gonna break it up in parts because Renault Pharm is just one of those things really one to understand. I was really shocked, I think it was yesterday of there about it, I was like, oh wait, I feel like I've covered all pharmacology at least that's tested commonly on the USM and the step one exam. But I noticed that I was like, we Renault, Renault, Renault, I don't seem to remember having made any Renault podcasts and I really did look through the entire website and didn't see anything like that and I was perplexed so I think it makes sense to make a Renault podcast, obviously for the purposes of the USM and the step one exam. So let's jump right into it. And again, I will talk about like Renault Pharmacology but again I'm gonna talk about it from the context of how the material will likely be tested on exams. So let's go ahead and begin. Right so obviously right Renault Pharmacology is something that you probably would never be able to understand if you don't have a good understanding of the Renault and your tensinolosterone system. Right? So remember that Renault ultimately comes from the Jocstag Lumerola cells which are subset of cells that constitute the afrin material. And this Renault converts and your tensinoligen right which actually does come from the liver to 100 tensin one.

And then that and your tensin one is converted to 100 tensin two by and your tensin converting enzyme which you'll find in the endothelial cells of the long right like the long capillaries. Right? And the thing is and your tensin tweets super high to know all its different functions for the exam right. So and your tensin two for example it goes to the super optic nucleus of the hypothalamus right so that you can release ADHD. Remember don't confuse the super optic nucleus of the hypothalamus releasing ADHD to the parvin trickle nucleus of the hypothalamus releasing oxytocin don't confuse those two things. And you may say divine do I need to know these nuclei of the hypothalamus for step one. What do you think? You better know them right? These are things that show up all the time on the exam. And then another function of 100 tensin two right it's it actually increases a systemic vascular resistance right. So the thing is that actually releases blood pressure right it's a very powerful viso constrictor. It does this by binding to the endotensin two type one receptor. Okay. Again there are certain receptors like drug receptors that your friends at the Mbimi really want you to know like in excruciating detail. They like you to know the receptor that is blocked by the like the ADP receptor blockers in the world of hematology right so like your clopidogrel your prasogrel your ticagrelor right.

Those block the ADP receptor but again your friends at the Mbimi realize that every human being has memorized the word ADP receptor. So the name they go after on exams these these is the P2 Y2 overseptor. That's something you certainly want to commit to memory. Another classic one is the lucotrain receptor right. So if you remember like like boxy genies converts our archedonic acid to lucotrain right. And the thing is I mean you can inhibit lipoxy genies to shut down the lucotrain pathway with a drug like xyloton or you can actually block the lucotrain receptor by giving drugs like come on to Lucas danza for Lucas right. So that receptor is known as again lucotrain receptor right. But the thing is your friends at the Mbimi prefer that you learn it as the cis LT1 receptor. So CYS LT1 receptor okay. So I would encourage you to not just remember oh hundred tenzin two receptor no. Remember that the hundred tenzin two receptors the hundred tenzin two type one receptor okay. That is the receptor that is activated by hundred tenzin two to cause an increase in vascular resistance right. So causes viso constriction. And then another thing that hundred tenzin two does is actually goes to the zonal glomerulosa of the adrenal cortex right. And in so doing that it stimulates the release of our dosterone right. Remember the adrenal cortex has like the zonal glomerulosa that secretes our dosterone the zonal fasciculata that secretes um glucocorticoids like cortisol.

And then the zonal reticularis that releases sex steroids primarily dgees okay. So again those are high yield things to know. And remember that the zonal fasciculata and zonal reticularis under the control of ac th okay. Adrenal corticotropic hormone. But the zonal glomerulosa is actually not under the control of ac th for the most part. It's more under the control of the renal and dredense and our dosterone system. So and dredense in two right goes to the zonal glomerulosa of the adrenal cortex okay. That stimulates the release of our dosterone. And the thing is our dosterone has a myriad of functions right. Some very high yield functions you want to know for example right. So the first thing is and I will talk about these different transporters because again review is always helpful. I'll talk about them probably like in the next podcast. So that will make a lot of mention of them in this podcast. But the thing is our dosterone if you go to the level of the distal convoluted tubio it increases the activity of the sodium chloride simporter that you find on the urine side okay. So that helps with increasing like sodium chloride absorption so water follows along side. Our dosterone also you know at the level of the principal cell of the distal nephrine it actually increases the activity of the inek channel okay. And if you increase the activity of that inek channel most sodiums will be reabsorbed right.

If sodium is already absorbed that will create negative charges on the urine side of the principal cell. That will drop potassium out of that principal cell right. So that's why whenever a person has high levels of our dosterone at play they will have a mild hyperneutrhymia right. But you have a hypochylemia as well okay. And then another thing that our dosterone also does is it increases the activity of the proton pump that you find on the surface of alpha intercalidity itself right. So if you increase the activity of that proton pump you don't put a lot of protons in the urine right. That would ultimately cause a metabolic alkalosis. That's why again if a person has a hyper our dosterone state they tend to get a metabolic alkalosis they tend to become hypochylemic already described that they tend to become hyperneutremic and they tend to become hypertensive right. Then you should understand the mechanism behind that hypertension as being a case of urebsobinatonous sodium so water will follow along side so your blood volume expands so your blood pressure expands. Now what are some high urebsobinatonous sodium step one that again again if you've listened to any of my podcasts you see that oh even if I title a podcast like Renovarmacology or whatever right. I try to talk around and integrate multiple fields with that.

So the thing is if you're thinking about step one right remember that angiotensin like in addition to converting angiotensin one to angiotensin two angiotensin converting enzyme actually breaks down bradykinein okay to inactive metabolites. So the thing is if you give an ACE inhibitor right you will actually increase the levels of bradykinein right. And by increasing levels of bradykinein remember bradykinein is a very good bronchoconstructor right. So people can get like an airway like reactive airway style response when they take an ACE inhibitor and bradykinein also actually increases vascular permeability right. So people can actually get a dima with that right. So the thing is the elevated bradykinein it kind of explains the dry cough side effect that is classically same with the ACE inhibitors okay. For the most part you do not get this dry cough side effect when you're taking AR Ps and angiotensin receptor blocker. Now with this said you definitely want to make sure you remember this enzyme known as C1 estri's inhibitor okay. Many people make this like fetal mistake on MB Ms. There is don't just say oh this person has a deficiency of C1 estri's that's at least for the purposes of the USML's that's not the way I would want you to remember things. Think about things more in terms of a deficiency of C1 estri's inhibitor. The full enzyme name is not C1 estri's it is C1 estri's inhibitor.

It is very critical to make sure you understand this because I've seen people host on the USML's by saying oh C1 estri's versus C1 estri's inhibitor. So C1 estri's inhibitor it's an enzyme it's actually another enzyme that helps with breaking down bradykinein. So the thing is it breaks down bradykinein so if for example a person has a C1 estri's inhibitor deficiency right then you want to try to avoid because these people are right think about it so let's say you have like two major bradykinein break down pathways in the body. One pathway is ACE the other pathway C1 estri's inhibitor and then a person let's say you know they have some genetic snafu and they have a C1 estri's inhibitor deficiency you've taken out one of their major pathways for breaking down bradykinein. Well if you give those people ACE inhibitors all right you've knocked out the second major pathway that they depend on so they have effectively no real pathways for the breakdown of bradykinein. So when they have that right they are levels of bradykinein will go up significantly right and they can get hereditri and juadema with that right because again I described some functions of bradykinein already I said bradykinein increases vasculoprimiability causes bronchoconstruction and things like that.

Now let's what if you get a question on the USM List that says how do concentrations of you know like things let's say like angiotensin-1 and angiotensin-2 how do their concentrations change as you traverse as you go from the pulmonary artery to the pulmonary vein. I would hope you're telling me that the angiotensin-1 concentrations actually decrease as you go from pulmonary artery to pulmonary vein right because remember it essentially encounters those endothelial cells in pulmonary capillaries that contain the angiotensin convertin enzyme right but on the flip side angiotensin-2 concentrations would increase right you may say divine it's kind of like a benign one dim point I promise you it's a benign one dim point that is very high yield to know for the USM List. Now the thing is in fact maybe think of this podcast as like a high yield surrounding renal from a college podcast because renal from a college is so high or but the thing is your friends at the MBME find multiple multiple ways to tighten to like many other topics right so it's again kind of high yield to understand these things and understand them are pretty well. So the thing is remember that your arterials are the blood vessels that directly feed capillaries. On the flip side your venules are the blood vessels that directly drain capillaries. Now the thing is there are drugs like hydrolyzing hydrolyzing is a selective dileter of pre-capillary arterials.

Another drug class that works by selectively diluting pre-capillary arterials are the dihydroperidine calcium channel blockers okay so drugs like amlodopin, clevidopin, phyloidopin, stuff like that right so those drugs they selectively dilute pre-capillary arterials. So think about it if you dilute the arterials that feed capillaries what happens to the hydrostatic pressures within those capillaries.

I hope you're telling me the increase right they should increase because you're sending more blood to them because you're dilating the blood vessel that precedes those capillaries right so pre-capillary arterials if you dilute them by giving like a dihydroperidine calcium channel blocker for example the hydrostatic pressures in those capillaries will increase and if hydrostatic pressure is increase if you're thinking about starling forces right that will promote fluid extravacation into the interstitial space so that will cause a dima that is why peripheral adema is a very common side effect in patients that are taking dihydroperidine calcium channel blockers that is one thing your friends at the USM will expect you to know but there's more the thing is well you have that problem it sucks how can I fix that the thing is if you want that to fix the peripheral adema that arises as a side effect of taking a dihydroperidine calcium channel blocker if you then make sense that you want to give something that can potentially decrease those hydrostatic pressures in the capillaries that are causing the adema right so think about it what would you ideally want to do to the post capillary venials if you wanted to fix the peripheral adema that is associated with taking a dihydroperidine calcium channel blocker well I would hope you're saying to delete those post capillary venials right because if you delete the post capillary venials you would have increased drainage from those capillaries and if you drain those capillaries better that will decrease the hydrostatic pressures well guess what it so happens there is a drug class that does that and that's what I'm talking about it in Reno from ecology those are your ACE inhibitors you know ACE inhibitors they actually very selective post capillary venials okay so they actually very I mean they have post capillary venial dilators so t

hey are very good for treating the peripheral adema associated with taking a dihydroperidine calcium channel blocker now if a person has a remaladry stenosis right I mean they will classically describe like an old guy on mbm exams that has a flung has a resistant hypertension they've tried multiple drugs his blood pressure doesn't seem to be coming down I guess an analogous disease in the younger focus especially the younger women on mbm is would be like fibromuscular dysplasia okay so those people tend to have like abdominal bruise flung bruise and all that stuff that's why if you're doing the physical exam right way you're doing like an abdominal exam and they tell you oh I'm listening for abdominal bruise we effectively trying to listen for especially if you listen on the flung you're trying to listen for renal adry stenosis that's old guy on mbm exams or fibromuscular dysplasia that is young female on mbm exams and one thing that classically accompanies renal adry stenosis so any thing that causes like super bad hypertension is avnican atero venous naked in the eye okay so naked n i c k i n g so naked and then anger okay so avnican that's a classic um foundoscopic finding people that have resistant hypertension or like malignant hypertension or people that have like renal adry stenosis for example because again remember that renal adry stenosis can cause bad bad bad bad bad hypertension and the thing is hypertension vastly increases our presence risk for stroke right hypertension is the biggest risk factor for stroke hypertension also causes like renal disease I mean like literally hypertension and diabetes are probably the two actually they are not probably they are the two most common causes of nstitriinal disease in the us so now what are the things that trigger release of renal right so let's again continue on our renal journey here so some things that trigger

the release of renal right if you hypoper fuse the afren arterial that will trigger renal release because the gg cells are like oh crap I'm not seeing enough blood volume well I got a spurs of blood volume by up in the activity of the renal adry stenosis system another thing that can also trigger renal release is if you activate beta one receptors so the thing is classically most med students think that oh beta one receptors I find them only on the surfaces of cardiac myocytes that could not be further from the truth you find beta one receptors on the surface of cardiac myocytes so the increase heart increase heart rate increase our contractility so the appositive by activating a beta one receptor you have positive chronotropic so increase heart rate and positive inotropic increase contractility effects but in addition to that you also increase the release of renal because they are actually beta one receptors at the level of the afren arterial of the nephron okay so that's very high you to know now if you also have low concentrations of like sodium chloride that's detected by the by the macular denser okay by the macular denser that will also trigger the release of renal the thing is the macular denser they are again there are subunit of cells in the nephron especially more so like the distal convoluted tubules they sense they're like chemical sensors they sense like sodium and chloride concentrations if they sense low sodium or low chloride these secret factors that tell the gg cells to secret more renal and the thing is again I'm just seeing this from the perspective of the person that has done a crap ton of renal research actually I still do a ton of renal research believe it or not so I've probably looked at like more than 50,000 pathology images of the kidney but essentially the thing that happens here is if you actually look and on things on a histologic basis

the macular denser cells actually closely fettered to the gg juxtaglomerula apparatus if you look at them histologically even if because many times if you're trying to learn things like linearly like oh the loop of hand release to the distal tubule and all that stuff you may kind of lose sight of like some important things but the thing is geographically in the nephron the distal the macular denser cells of the distal convoluted tubule are almost like directly opposed to the other cells that make up the juxtaglomerula apparatus right like the gg cells or the extra glomerula mesangial cells for example okay so again those are all high-eal things I guess maybe more for the purposes of understanding to keep in mind for example so I said again low concentration of sodium and chloride sense by the macular denser cells those are that ultimately causes an increased release of renal if you actually give a person like aspirin or like an inset the release of renal actually increases because if you actually think about it what does aspirin or most insets do reading hippy cycloxygen is well if you inhibit cycloxygen is right what will happen to your levels of prostaglande it will go down well if your prostaglande levels go down what happens to the afferent material does it constrict or does it dilute it constricts and if it constricts that means your gg cells will start sensing low flow and if this sends low flow they will begin to secret more reading that is why if you actually a prefer person is on like insets or aspirin for like prolonged periods of time that can actually cause like a reactive hypertension in a sense okay and I mean remember right out of the stern and this is something that you like daily learning like an endocrinology block in fact I'll say probably some of the stuff I'll mention from now although actually maybe the next five minutes I'll mention a lot more r

enal stuff but the thing is your friends at the mbmi love to integrate renal with endocrine so I'm going to talk about some endocrineology in the context of renal if you've not had an endocrinology block yet you should still be able to understand what I described because I'm going to try to describe everything in three good detail so the thing is remember our duster and rate it's a steroid hormone right so its receptors will not be found on the surface of a cell its receptors will be found inside a cell okay and the thing is when our duster right because it's it's a steroid hormone it should be able to cross cell membranes without issue it gets into the cell it binds to the aldosterone receptor okay that receptor and aldosterone then goes to response elements on DNA okay so that you can increase the synthesis of the stuff that you want so let's talk about let's do some aropushing here I don't mean I know some people have studied hyperventilating oh no the virus is that talking organic chemistry now aropushing in the context of the mbmi is our way you get questions where they give you like four or five different things and then they put all these hours flying all over the place like some hours going up some hours going down and all that crap so I want to do a bunch of those questions probably for the next 10 to 15 minutes and because this stuff is kind of technical after I do this I think I'll go ahead and pause this podcast and pick up in the next one on on a renal pharmacology so and the next podcast fair warning I'm going to describe all the transporters in the nephron in great detail and you may say do I need to know those transporters in great detail for the usmly exams yes you do okay more so for the usmly step one exam but also believe it or not for the usmly step two ck exam and the step three exam these transporters show up all the time okay I promise you as a

person that has taken all the us at least all the usmly exams that currently exist knowing those transporters is just one of those things that will set you up very well both for your future taking nbm usmly exams and also for your future taking maybe I guess met school exams and also for your future practicing as a clinician believe it or not so the thing is let's assume a patient takes an ace inhibitor what happens to their levels of reigning it should go up right because think about it what does an ace the thing is whenever you get these arrow questions the first thing should ask yourself is okay what's happening when when I give when I introduce this intervention if you give an ace inhibitor you're inhibiting and you're tensing converting enzyme so you're essentially inhibiting the conversion conversion of 110.1 to 110.2 so if you're preventing the conversion of 110.1 to 110.2 well guess what your levels of 110.1 should increase and your levels of 110.2 should decrease and if your levels of 110.2 decrease then you will have less stimulation of our dostron release from the zona glomerulosa of the adrenal cortex so your industrial levels go down and if your industrial levels go down that means you'll stop absorbing sodium in the in the nephron and water you'll be essentially by not reabsorbing sodium you'll also not be reabsorbing as much water so your blood volume will decrease your blood pressure decrease and if your blood pressure decreases you'll have less perfusion of your afrin material so all that do to the release of ringing now actually increase ringing release okay so that is why if a patient is on an ace inhibitor the levels of ringing and angiotensin 1 both go up but the levels of angiotensin 2 and our dostron both go down now what if a patient is placed on an angiotensin receptor blocker right if a person is placed on an angiotensin receptor blocker wha

t should happen to their levels of ringing it should go up right because again by giving an angiotensin receptor blocker right you will block every activity of angiotensin 2 and by blocking every activity of angiotensin 2 well guess what you will not you will essentially again block those angiotensin 2 receptors that you find in the zona glomerulosa of the adrenal cortex so you'll stop releasing our dostron so your dostron levels will fall if your dostron levels fall you'll stop reabsorbing sodium and water in the nephron so your blood pressure will go down so your blood I mean your blood volume will go down so your blood pressure goes down if your blood pressure goes down you will hypo-perfuse the afrin material if you hypo-perfuse the afrin material you will increase your release of ringing because you rev up that you make those gg cells a little more and see okay so you make more ringing you make more angiotensin 1 you make more angiotensin 2 but our dostron will remain persistently low because those angiotensin 2 receptors have been blocked so you will not be able to observe angiotensin 2 style effects so do you see the subtle differences in these arrows if you are comparing taking an ace inhibitor to an angiotensin receptor blocker right because in an ace inhibitor if you take that your ringing and your angiotensin 1 levels go up but your angiotensin 2 and all those throne levels go down if you take an angiotensin receptor blocker your ringing angiotensin 1 and angiotensin 2 levels all go up but our dostron levels are still still down now what if you took this drug known as alesq alesq right so A L I S K I R E N alesq alesq alesq is a direct inhibitor of ringing right so what actually happens your ringing levels if you take alesq and actually it goes down right so your ringing will go down well if your ringing goes down remember ringing is the feet stock for the

ringing and your tensin of dostron system if your ringing goes down well guess what your angiotensin 1 will go down if your angiotensin 1 goes down and your tensin 2 will go down if your tensin 2 goes down your aldostron will go down so everything is low when a person is on alesq but what if a person took spironolactone spironolactone is an aldosterone receptor antagonist spironolactone is an aldosterone receptor antagonist well if you took an aldosterone receptor antagonist right you will not observe the functions of aldosterone right so that improves the activity of the sodium chloride transporter I mean same powder that you'll find at the level of the distal convoluted tubule or that activity of helping the inech channel at the principal cell work even better or those proton pumps right at the alpha intercalculated cell working better all those would not happen right so the thing is if those things do not happen right you not be absorbing sodium chloride in the nephron so water is not following alongside so your blood volume goes down your blood pressure goes down you hypoperfuse the afrin material so your ringing will go up your angiotensin 1 will go up your angiotensin 2 will go up your aldosterone will also go up because the aldosterone you're not getting its effect so that negative feedback just is not there so everything will be up okay so the thing is again make sure it's like super super important that you understand these scenarios I just described these things have shown countless times on the USMAD exams now another thing you want to keep at the back of your mind is you can also see how they can stretch these questions to begin to talk about things like sodium potassium acid base like oh what happens to the blood P what happens to the blood hydrogen ion concentration stuff like that so let me give you an example with spironolactone for present xperinolact

one right which is an aldosterone receptor blocker right you're not getting the aldosterone effects right so instead of becoming hyper nitremic you'll be hyponytrymic because you're feeling to reabsorb sodium at the level of the distal convoluted tubule and also at the level of the principal cell of the collecting duct those people will also get hyper chylemia okay hyper chylemia hyper chylemia because again if you're not reabsorbing sodium at the level of the principal cell of the collecting duct you do not create those negative charges on the urine side that serve to drop potassium out of the principal cell okay so you actually become hyper chylemic right and then think about it if those alpha intercalated cells are not working at least those proton pumps on the urine side of the alpha intercalated cells are not working then you're not dumping protons into the urine and if you're not that means you're retaining those protons so you get a metabolic acidosis right so the blood P should fall in a patient that is taking spironolactone the same things you would also observe in a patient that's taking a plerinone a plerinone is another aldosterone receptor antagonist the only benefit a plerinone has over spironolactone is that a plerinone just blocks our aldosterone receptors but spironolactone in addition to blocking our aldosterone receptors it also blocks androgen receptors so you can cause any comastia as a side effect now what if the telioprision has like renal arteries stenosis of fibromuscular dysplasia let's sort of keep this train of reigning and you're tensing one and you're tensing two bloody bloody blood going so if a person has renal arteries stenosis of fibromuscular dysplasia obviously those people will stop perfusing the alpha intercalate right so again the renal will go up and you're tensing one will go up and you're tensing two will go up our industrial

will go up right now what if a person has adicence disease what if a person has adicence disease remember adicence disease is primary adrenaline sufficiency okay so it's like an autoimmune destruction of the adrenal glands so the adrenals get all screwed up especially most of the adrenal cortex so if you destroy the adrenal cortex right well you will no longer be able to make cortisol you will no longer be able to make our duster you will no longer be able to mix at least DGS the sex steroid DGS right so if that happens well think about if you're not making our duster right then you're not making cortisol remember cortisol actually has a permissive effect on the sympathetic nervous system you may see divine how there are many ways but one big one the expected to know the USMLA exam says there's this enzyme that converts noripinephrine to epinephrine it's known as PNMT phenyl I think ethynellamine N-method transfer is or something like that that enzyme so that enzyme already converts noripinephrine to epinephrine right and I mean essentially right phenyl ethynellamine N-method transfer is right so it uses it essentially adds a methyl group to noripinephrine to make epinephrine so it should maybe help you remember that SAMS adenosyl methyonine is a cofactor for that enzyme believe it or not that's something floridly high to know for the USMLA's a SAM is a cofactor for for PNMT okay remember methyonine is a very good a methyl group carrier in the body so so the president has that essence disease and I'm making our duster on right then I'm making cortisol so obviously your blood pressure your blood volume is going to fall I mean your blood pressure is going to fall right because you're not getting that help me reabsorbed sodium chloride in the net front kind of business going anymore okay and again that permissive effect of cortisol on the sympathetic nervous system where

it activates PNMT in the adrenaline dollar right to help you convert like noripinephrine to epinephrine is no longer there so your blood pressure falls if your blood pressure falls that will spurs up the activity of the reneine undutensin our duster on system right because you'll be hyper-prefusing the afrin material so your reneine will go up your undutensin one will go up your undutensin two will go up but your duster will not go up because even if there is undutensin two around your adrenal cortex is all screwed up so like the site of production of our duster on is literally gone so your duster levels will fall one thing I will go ahead and say is you should be able to contrast primary adgenial insufficiency with secondary adgenial insufficiency with reference to our duster on levels right so whenever you have a primary problem in endocrinology it means is at the level of the organ itself the gland itself right so like the adrenal gland is screwed up in primary adgenial insufficiency right but the thing is if you have a problem one level higher let's say at the level of the anterior pituitary gland there'll be a secondary adgenial insufficiency all right the thing is when people have secondary adgenial insufficiency their cortisol levels will be low because basically secondary adgenial insufficiency means you have an acthed efficiency so their cortisol levels will be low their six steroid levels like dhias primary will be low as well but the thing is that our duster levels will be just fine remember very early in this podcast I said that the zona glomerulosa is not under the control of acthedage so if you have an acthedage problem your zyloclomerulosa works just okay okay so you have normal levels of our duster in secondary adgenial insufficiency where you have decreased levels of cortisol and your six steroids that are supposed to come from the adrenal gland agai

n more commonly dhias and you should also at least hopefully remember that if a person has adgenial insufficiency of any kind especially like primary adgenial insufficiency ekei adescent disease their your synafial levels go up okay their synafial levels go up and that's something you'd want to know like for your future in medicine essentially it shows up on all the usml exams shows up on the medicine show of exam shows up on a ton of stuff right so because remember cortisol actually causes epoptosis of your synafials right so if your cortisol levels are down because your adrenal glands have been destroyed well you have decreased epoptosis of your synafials so your synafial count should go up you should also remember right that if a person has adgenial insufficiency their white blood cell count should ideally go down because there's decreased de-margination of neutrophils right again those are all things you kind of want to make sure you know for in-beaming exams now what if a person has the disease concentrate if a person has concentrate what should happen to their levels of ringing and your tensing one and your tensing to an outdoster well think about it concentrate is a disorder again I told you whenever you see these are questions always define the problem that is being tested when you don't define the problem and just say oh I'm just gonna start from anywhere I can almost assure you very likely it's only if you like your your command of physiology is very good which unfortunately is not the case for many medical students if I define the problem first and then go from that point before you then begin to build other parts of the arrow pushing question so if a person has consent drum in consent drum you have an adenoma in the adrenal gland more likely in the adrenal cortex that's making a ton of outdoster right so obviously if you're making a ton of outdoster right

you know again you will increase the activity of that sodium chloride simple order you may see divine you repeated the same multiple times repetition always helps especially in renal and you gonna do a lot of repetition I guess let me call it targeted repetition because I'm repeating the same thing what in different contexts I will do the same thing in the next renal farm podcast because those transporters are bare to learn for many people but the thing is once you learn them well the first time and see how they apply pharmacology wise which is what I'm going to do right I'm not just gonna give you random names of transporters to memorize no I'm gonna talk about the transporters and then I'm gonna talk about even the context of renal from ecology and if you learn those things well you should really not forget them that's that's the truth so con syndrome a general adenoma secretion of creatinine of an adostro right so you will increase the activity of that sodium chloride simple order that you find that the level of the distal convoluted tubule right and you'll also increase the activity of the inek channel that again you'll find that the level of the principle cell of the distal nephar so those things will increase your blood sodium water will follow alongside so your blood volume increases your blood pressure increases right so you would hyper not high pull hyper perfuse the afraid material if you're hyper perfuse the afraid material that will dial down the ringing and jatanson system right so those people's levels of ringing will go down okay the levels of angiotensin one will go down the levels of angiotensin tool also go down as well okay that is why you actually use the plasma or dostro to ringing ratio so the plasma or dostro to ringing ratio to to string let me not string let me not see diagonals because to diagnose con syndrome you do like some salt suppressio

n crap but that's more for endocrinology so in a person that has con syndrome right so you measure the plasma or dostro to ringing ratio be elevated because the dostro is going up because the adenoma is secreting our dostro but the ringing is coming down okay I would hope you're able to contrast this with Rinaladristinosis where the out dostro and ringing are both going up right so the out dostro to ringing ratio will be normal right it should be like less than 20 or there about so different resources use different numbers versus con syndrome that has an elevated plasma or dostro to ringing ratio now what if a person has one of the congenital adrenal hyperplecious and they have it from an 11 beta so this is again a very nice way of friends at the Mbimilov to integrate endocrin with Rinaladristinosis what if a person has an 11 beta hydroxylis deficiency for those of you that have not reviewed endocrinology let me talk through this real quick basically for person has an 11 beta hydroxylis deficiency they will not be able to make they will not be able to make our dostro and they will not be able to make cortisol okay it's an endocrine disorder I think I've either talked about this more fully in an endocrine podcast I've made in the past or I will talk about it more fully when I make an endocrine related podcast but basically the thing that happens is that if people have an 11 beta hydroxylis deficiency they will not be able to make our dostro or cortisol right but the thing is 11 beta hydroxylis if you have that deficiency you have a build up of a compound known as 11 deoxycoticostero okay I'll see that again 11 deoxycoticostero so 11 a hyphen and then DEOXY CORTI COSTE RONE 11 deoxycoticostero the thing is 11 deoxycoticostero is a special compound that has partial agonist activity at mineralocodicoid receptors I'll see that again 11 deoxycoticostero is a compound that h

as partial agonist activity on mineralocodicoid receptors so the thing is you get a partial outdostroin effect when a person has an 11 beta hydroxylis deficiency so the thing that happens is if you have that 11 beta hydroxylis deficiency again just by virtue of because that enzyme comes upstream of the production of our dostroin and cortisol your dostroin levels will be low okay your dostroin levels will be low but look at why your friends at the NBME will be like having this a sheepish green when you're writing this kind of question your levels of our dostroin will be low so you will think that means because there's no negative feedback block rate I mean raining will be high and you're tensing one and two will be high that could not be further from the truth okay so you got to be careful there on the USM Ls the thing is by virtue of the enzyme defect you know dostroin levels are low granted but one of the things that builds up because you have that block in that pathways again this magic compound I talk about 11 deoxycoticostero and because 11 deoxycoticosteroin has partial agonist activity on mineralocodicoid receptors you do get an outdostroin-like effect so you actually increase the reabsorption of sodium and chloride at the level of the nephron so that will actually raise your blood volume raise your blood pressure so you'll actually hyper-perfuse the afferent arterial so people that have 11 beta hydroxylase deficiency will have low levels of raining low levels of angiotensin one and low levels of angiotensin two and again by virtue of the enzyme defects they'll also have low levels of outdostroin okay again I really hope you understand this is floridly high autonone for the USM Ls the one example and then what if a person has a 21 hydroxylase deficiency that's another adrenal corticone enzyme defect in fact this is actually the most common cause very high aut this

is the most common cause of congenital adrenal hyperplegia okay um I guess before I talk about the 21 hydroxylase deficiency so we'll be see define what's this crap called congenital adrenal hyperplegia we'll think about it um by in general with these conditions you have trouble making out dosterone or cortisol well guess what if you're not making out dosterone or cortisol well if you're not at least more so the cortisol right by not making cortisol you have no negative feedback at the level of the anteriority right so your act H levels go up and I mean literally act stands for adrenal corticotropic hormone it's a hormone that is tropic to the adrenal cortex so because the levels of act H go up significantly with these are congenital adrenal hyperplegias the thing that happens is um you're gonna uh very widely stimulate the adrenal cortex so the adrenal cortex expands significantly in patients with any of these disorders and these patients also tend to get you know pretty significant a skin hyperpigmentation because act H as it so happens comes from a compound known as pomc pomc like p o m c pro opio melano cortin pro opio melano cortin um I mean the name literally tells you the things that come from the compound pro opio opio and opioid comes from pomc that opiod is beta endorphine and again I'm seeing all these not because I like to hear myself speak I'm seeing all these because these things show up a ton on the usml exams right so pro opio melano cortin right so um pomc gives rise to an opiod beta endorphine beta endorphine acts on new opioid receptors so pro opio melano melano melano sites stimulate in hormone comes from pomc as well stimulate melano sites right so that's why you have skin hyperpigmentation in a person that has a congenital adrenal hyperplegia or even a general insufficiency of any cause right as uh let me not say of any cause most specifically like

a primary adrenal insufficiency uh because anything that essentially will raise your act H levels will cause skin hyperpigmentation and then um so pro opio melano cortin so the cortin stands for the act H okay so again I really hope you understand these things uh again we see the vine you're going into a lot of detail but I promise you I have thought and treated thousands of people that take these exams these things shop a ton on mbme usml exams okay so back to what we're talking about and then we're on the sub right so if a person has a 21 hydroxylis efficiency again like I said this is the most common cause of congenital adrenal hyperplegia these people have no outdoor stirr all right they'll have no cortisol but actually in 21 hydroxylis deficiency your 11 deoxycoticosterone does not build up this enzyme this enzyme is more upstream of 11 deoxycoticosterone so you don't have that magic compound that has like partial agonist activity on mineralocodic oil receptors so guess what by virtue of the enzyme deficiency you don't make our duster so that's a given your duster levels are going to be long right but because you are not making our duster and you're not making cortisol or you're not making the magic compound 11 deoxycoticosterone that has partial agonist activity on mineralocodic oil receptors well your you're not reabsorbing sodium chloride at the level of the distal convoluted tubule you're not reabsorbing sodium through that inaction at the principle set of the collecting duct so your blood sodium goes down so your blood volume goes down so your blood pressure goes down right so your blood pressure goes down well guess what you will you will high-po perfume the afrin material if you high-po perfume the afrin material well your reading levels will go up because the gg cells will start freaking out your reading levels will go up and you're tensing one levels will

go up and you're tensing two levels will go up as well okay so again these are all higher things so can you see that two enzyme deficiencies within the same gland 11 beta hydroxylase deficiency versus 21 hydroxylase deficiency which is more common right can cause widely varying effects on like renein and you're tensing one and you're tensing two and our duster levels right so again that's why your friends at the mbme love to test this stuff so i'm gonna go ahead and pause as i do at the end of every podcast i do offer one on one tutoring for all the usml exams step one to ck two cs step three okay i do also offer one on one tutoring for like med school preclin collect exams and the third year clerkship shelf exams okay and then also do this thing that i've talked about at nausea more than last couple of podcasts that i call longitudinal tutoring where essentially tutor you through let's say you're in newly minted first year second year tutor you through all your class exams and then i tutor you during your daily period but the thing is as i tutor you through all those class exams i also tutor you for step one at the same time so you essentially reviewing step one material as you're going through your class material with a person that is very well versed in that material in that content i guess same thing with a third year mesh student studying out your third year i tutor you for all your shelf exams at the same time i'm also tutoring you for step two ck like teaching a test-taking strategies and all that stuff and teaching your content as well so that again when you hit your daily period you're like super well prepared like everyone i've done this with has been like wildly successful on the usml exams and then if you have like a college buddy that needs tutoring for genkame o-cam physics bio-cam histology and physiology of a tutoring for all those things and then if

your college student applying to med school so like an amca application or a med student applying to residency so an iris application i do one-on-one like consulting or advising for those i've worked with tons of people through many cycle admission cycles and the vast majority of those people have much that their first choices right so things like personal statement help little recommendation help mock interview help ediline and reveal your iris application those are things i don't do so if you know anyone that needs all those either reach out to me through the website or send me an email at divine intervention podcasts with an sdn.gmail.com so i do hope you get you got something from this podcast i'll pick up from here in the next one have a wonderful rest of your day god bless you i'll see you next time thank you

Angiotensin-Converting Enzyme (ACE).

P2 Y12 receptor.

1) Distal Convoluted Tubule (DCT), increasing $\text{Na}^+/\text{Cl}^-$ cotransporter activity. 2) Principal cells of the collecting duct, increasing E NaC channel activity and proton pump activity ($\alpha$-intercalated cells).

A/V nipping (Arteriovenous nicking).

11-$\beta$ hydroxylase deficiency.

With an AC Ei, both Renin and Ang I increase, but Ang II decreases. With an ARB, Renin, Ang I, AND Ang II all increase, but Aldosterone remains low (due to blocked $\text{AT}_2$ receptors).

They sense low concentrations of sodium or chloride in the filtrate and trigger renin release.

Zonal glomerulosa; primarily controlled by Renin-Angiotensin System (RAS), not ACTH.

Dry cough; due to increased levels of bradykinin, which is a potent bronchoconstrictor.

11-deoxycorticosterone.

Primary AI: Low cortisol, high ACTH (due to lack of negative feedback). Secondary AI: Low cortisol, low ACTH (pituitary failure).

Conn's: High Aldosterone, Low Renin/Ang I/II. Renal Stenosis: High Renin, High Ang I/II, Normal-High Aldosterone (depending on severity).

S-adenosylmethionine (SAM).

Zonal glomerulosa; primarily controlled by Renin-Angiotensin System (RAS), not ACTH.

Dry cough; due to increased levels of bradykinin, which is a potent bronchoconstrictor.

11-deoxycorticosterone.

Primary AI: Low cortisol, high ACTH (due to lack of negative feedback). Secondary AI: Low cortisol, low ACTH (pituitary failure).

Conn's: High Aldosterone, Low Renin/Ang I/II. Renal Stenosis: High Renin, High Ang I/II, Normal-High Aldosterone (depending on severity).

S-adenosylmethionine (SAM).