you you you you you you all right good morning everybody thank you so much for joining me we have a jam-packed classroom today so all of you are just you know very I'm sure passionate about studying for the USMLE and today I'm going to be kind of going through a very high yield topic something that's near and dear to my heart renal physiology but first why don't I get to why don't I have the opportunity to get to know all of you all can you type into the chat where are you all from I would just love to know either city or country that would be so awesome all right great Wow awesome so we got some us Oh India international audience perfect Pakistan that is awesome Colombia wonderful Wow South Texas excellent excellent perfect well as you guys know you I mean this this exam basically has no borders and that's the beauty about medicine is you know it is so far-reaching and the profession itself is so noble and humbling and as myself just finishing residency it's been absolutely awesome to teach throughout residency and then also take care of patients so appreciate you all joining me and just wanted to kind of lay some ground rules before we start our presentation today now if you don't mind muting your audio it should already be muted and also if you have any questions feel free to put them in the chat box and towards the end of the session I will definitely get back to you all with those questions if you have any issues throughout the presentation try to kind of mess with the audio or the video and I will let you know if there's any Internet connectivity problems on my end but sounds like everybody can hear me right now so that is absolutely awesome so one question I'm gonna ask you all so you stay active and engaged because that's all that's what I'm all about are you guys pumped to learn some USMLE physiology let's let's go for it as I just have to make it as exciting for you as possible so are you guys all pumped all right Tina is look at that oh all right I'm getting a lot of yeses so that is great well first off I just want to start off by just saying thank you so much I mean I started this high grew kind of project and community a little over a year ago officially and it all just came from a passion for teaching a little bit about me and my good friend David Shaffer so I am actually a now graduated pediatric resident and I'm assumed to be fellow in pediatric intensive care so I'm going to be starting actually at the beginning part of this July so I'm actually very very pumped and David actually is a attending physician and he is a pediatric nephrologist by training and he does see general pediatric patients as well in the Cleveland Ohio but more importantly I mean despite being clinicians we are two passionate individuals that really want to change medical education we want to go from a very linear kind of model of learning to something that is integrative something that is active for you all right something that you can study right now and then in your clerkships in your residency fellowship you can apply and I think what's so unique about hi guru is number one we are a community secondarily we are very focused on USMLE step one and step two preparation because honestly that's kind of a stepping stone to get to your residency to get to those fellowships right we also are going to be very focused at hi group we are very focused on active recall rather than me just being like oh yeah so in pre renal kidney injury the B UN to creatinine ratio is greater than 20 for example I'm going to give it to you in a vignette manner because guess what we all have to practice like we play and when you practice like you play and you learn content and questions at the same time that is going to be an efficient way of learning so let's kind of just get into what we're going to be doing today well first what I'm going to do is give you the organization of the kidney I'm going to talk about glomerular physiology some clinical markers of kidney function filtration fraction and then what we're going to do is just take a trip into or through the nephron we're gonna start from the proximal convoluted tubules and end in the collecting duct and everything is going to be very us Emily oriented guys what I honestly did was I synthesized a lot of my own notes as I was going through step one preparation from you world first-aid path oma etc from BRS and Kaplan which are big physiology resources as well so as you will see this is a very integrative review and I hope that you stay active and engage with some questions that I'll be asking so you know put up the chat bar and stay really excited to continue to learn some of these concepts so let's do it I'm a very cheesy kind of guy and I do want to start off with a little bit of an inspirational quote so remember that true success is achieved by stretching oneself learning to feel comfortable when you are uncomfortable so I'll always push yourself and with that let's get into it now the first thing that we're going to be talking about is the functional organization of the kidney now as you know the kidney has an atomic components and it has functional components and sometimes you can relate the anatomy and the physiology together now what is the basic functional unit of the kidney I know there's bright and early in the morning why don't you guys type in a basic functional unit of the kidney what are we focusing a lot about yeah I got a lot of answers here yeah exactly everybody's saying the nephron and you're absolutely correct so the basic functional unit of the kidney is going to be the nephron now remember that with the nephron we have two flavors of nephron we have the juxta medullary as well as the cortical nephrons now which comprise a majority I'm gonna continue to have you guys engage what do you guys think majority of nephrons how many people say juxta good medullary or how many people say cortical type it in right now what do you guys think got one person saying juxta medullary hmm whoo this tough one right yeah absolutely so actually majority of nephrons are actually cortical nephrons and that's important for you to know the other aspect of the nephrons are going to be judged eventually so what defines structure medullary well jokester medullary is going to be a nephron in which there are long loops of Henle that penetrate into the medulla of the kidney remember the cortex is on the outside the medulla is on the inside and this functional organization of the kidney is very high yield for your step one so let's go into it in a little bit detail now as we see this is going to be a nephron and the long loops of Henle go into the medulla of the kidney and that is extremely important for you to know now let's go into an application question a patient with chronic kidney disease is found to be hypotensive in the ICU what portion of the nephron is most affected by this acute insult now this question yes it's an active recall question it's an application question and what I want to really highlight is yes in this in the setting there may be a couple correct answers however when we're talking about the difference between juxta medullary and cortical what we have to recognize is that the medulla from a macro anatomic perspective has a lower po2 and it is this medulla that is going to be most affected by the acute insult another correct answer in terms of hypoxia to the kidney decreased blood flow in this patient hypotension is going to be the proximal convoluted tubule USMLE loves for you to know that why because the proximal convoluted tubule is extremely metabolically active and thus it is going to be very susceptible to ischemic events hint acute tubular necrosis very nice breaching pathology there so medulla as well as the proximal convoluted tubule are going to be two areas that are particularly susceptible to ischemic injury now the key thing for you to know is that the medulla has these long capillary loops and long capillary loops is our going to be known as the fazer ekta and the basal rector are actually a branch of the peritubular capillary system but are we going to get to that but the Vasa recta are a branch of the peritubular capillary system now what we recognize is that there is slow flow through these vasoactive vessels and so when there is that slow flow that keeps the po2 the partial pressure of oxygen of the medulla lower than that in the cortex and when the partial pressure of oxygen and medulla is lower than the cortex that is the why the mechanism step one is all about mechanism that is why it is more susceptible to ischemic damage now what portion of the nephron is going to be hyper osmotic do we think the cortex or the medulla how many people say it is the either cortex or medulla type that in whoo everybody's getting this answer right now yes exactly very good very good exactly the portion of the nephron that is hyperosmotic that is going to be the medulla exactly have you guys heard of this concept counter-current multiplier system right the counter-current multiplier system the fact that you can concentrate your urine through various different osmolality zuv the medulla that is extremely important for you to know okay and relatively aisa's monic is going to be the cortex very good all right so next thing we're gonna be talking about is why is renal perfusion important and look highlight this concept by going through a sample question so a patient presents with shortness of breath and peripheral edema he has difficulty lying flat and exam reveals crackles on his lung exam hmm so as we read this what do we think the diagnosis of shortness of breath he has edema he can't basically live flat and some people are typing in the chat you're absolutely correct heart failure exactly this is all congestive heart failure and you guys are like excuse me this is the renal review not the cardiac well remember the body is all connected right so the likely presentation here is congestive heart failure and as you can see this patient has signs of fluid overload now if we continue on with this vignette the patient's ejection fraction is markedly low I eat under 55 percent and as cardiac output is calculated to be 2 liters per minute whew normal cardiac output about 4 to 5 liters per minute so just patient has severely compromised cardiac output now what percent of this cardiac output will the kidneys receive hmm and so what is very important for you to know is that the kidney receives about 20 to 25 percent of the cardiac output and I think that is extremely important for you to know ok and if we apply this this patient this patient has a kidney blood flow or a renal blood flow of 0.5 why because here's the cardiac output and 25% of his cardiac output is going to be his renal blood flow and that is really really important because as you can see normal renal blood flow is about 1.1 liters per minute okay 1.1 liters per minute and that comes from the fact that it is about 1/4 of cardiac output so this is extremely important for you to know for your us Emily questions and this is all going to be related to how cardiac output is related to renal perfusion all right excellent wonderful so the next thing that we're gonna be talking about is not only looking at the cortex and medulla but we're gonna dive into where the USMLE really likes to ask a lot of questions and that is going to be at the level of the nephron we have to first get some basic terms out of the way though as you can see blood comes in from the efferent arteriole and is going to leave via the efferent arteriole and here's the glomerulus right now they're after the efferent arteriole this is an important point right here and not many students know this and I really want to highlight this the efferent arteriole yes it goes back to the heart after a while right but the efferent arteriole extremely important for you to know is going to actually continue as the peritubular capillary system make sure you recognize that the whole aspect of reabsorption of ions the reabsorption of the ions from the P area here a PPD area into into the actual blood stream is going to be into the peritubular capillaries carry tubular surrounding the tubules and that's high-yield for you to know okay and we're gonna toy with this concept in the next slide now go back to what we're comfortable with yes this is the glomerular capillaries yes this is the Bowman's space the Bowman's capsule okay and what do you think process one is process one is when you are coming out of the glomerular capillaries and that is going to be filtration exactly that's going to be filtration excellent now what is going to be process number two ie from the P into the peritubular capillaries and that is going to be reabsorption exactly very good so filtration reabsorption and if you go the opposite way from the peritubular capillaries into the lumen of the nephron you are going to have secretion and finally number four is going to be excretion and so mathematically and conceptually if we think about it excretion excretion is going to be equal to your filtration - what you take out plus what you are going to add hmm let me say that again alright so here you have a bucket of money right I'm filtering that bucket of money okay fine take some out for taxes oh but put some back in because I was earning something from my side hustle okay so that is excretion is okay filtration - when I took out plus Kate what did I add back so this is a nice step 1s question and I want you all to read this question and type into the chat box what do you think the answer is so what change tends to increase peritubular capillary fluid reabsorption I'm gonna take a nap for 30 seconds and feel free to answer the in the chat box you you you all right we're getting some e we're getting some a's who sees who can we get some more i know there are more people here you you you all right so a lot of ease actually you know the answer is and we got a couple of C's as well the answer is going to be C all right so let's actually kind of go through this and why this is really important increase peritubular capillary fluid reabsorption is going to be all related to particularly where we have the configuration of the efferent arterial what the configuration of the efferent arterial is a ferrant efferent and peri tubular capillary system now if you have increased efferent arteriole or resistance this efferent is going to squeeze down so a fair efferent and the e front is going to tighten up and when that tightens up you have increased amounts of glomerular pressure and subsequently increased amounts of GFR now the fluid that is left here it's like squeezing that sponge that fluid actually is not even there because hey guess what we put it out here where the GFR is supposed to be and what happens as the blood goes and becomes a period tubular capillary system it becomes very rich in proteins and subsequently has a very high oncotic pressure and when it has a high oncotic pressure it is going to cause you to reabsorb reabsorb more more of the fluid and more of the ions because there is a higher gradient between the lumen of the kidney as well as the peritubular capillaries which now has an increase oncotic pressure and that's high-yield for you to know now increased renal blood flow may not directly increase the peritubular capillary fluid reabsorption it just is going to increase the GFR but if you squeeze down on the e ffort more glomerular filtrate is going to be coming out and you have a higher oncotic pressure of pulling pressure in the peritubular capillary space and that's high-yield for you to know now put it right here at the USMLE increased efferent arteriole or resistance they can say oh yeah increased levels of angiotensin 2 any state any clinical vignette that is going to activate ress okay so these thirds are to sinners and as we know that wrath and the the angiotensin ii concentrations are going to affect the efferent arterial alright continuing on when we talk about the glomerular physiology I want you all to answer this question so a patient is found to have elevated angiotensin ii concentrations what effect would this have on glomerular hydrostatic pressure we just actually talked about this hmm what do you guys think what effect would increased angiotensin ii concentrations have on glomerular hydrostatic pressure I'm seeing a lot of yes very good it is going to increase and the mechanism here is that you have a ferret arteriole or constriction let's go through it again a fern let Mary Alice be fair if you have constriction of the efferent you are going to cause a lot of glomerular back pressure and that is going to increase your GFR and obviously increase circular hydrostatic pressure now a patient is placed on NSAIDs for osteoarthritis this is a very high yield us Emily vignette now what effect would this have on glomerular hydrostatic pressure ooh this is interesting so NSAIDs go through what the mechanism of action of n senses n sets is a Cox inhibitor and downstream as it affects the arachidonic acid pathway it is going to reduce the amounts of prostaglandins if it reduces the amount of prostaglandins guess what you're a friend arterial is not going to stay as open a friend arterial is not going to stay as open because remember prostaglandins phase or diving things and if you're a fan territorial is not going to be as open guess what well you're gonna have decreased glomerular hydrostatic pressure so the mechanism here is that when you inhibit prostaglandins by giving NSAIDs you are going to decrease glomerular hydrostatic pressure because prostaglandins normally normally prostaglandins keep the air foreign territorial open summary here efferent arteriole under the control of prostaglandins 'if errant arterial under the control of angiotensin ii and i love for you to make that distinction in your mind because us emily questions are going to kind of play with that adage okay for example the incense question we're gonna be talking about the a fern for example increased amounts of aldosterone secondary to increased amounts of Rass that's gonna be the more easier okay excellent so let's kind of go through this a little bit more and these are all from your high-yield resources as we see if we constrict the afferent or the efferent arteriole excuse me as we constrict the efferent arteriole which is right here you are going to increase your capillary glomerular hydrostatic pressure and increase your GFR and that is extremely high yield for you to know actually one of the other questions that they can ask is a diabetic patient who comes in with proteinuria hmm why is that well as you remember from Fatima in diabetes you have preferential non-enzymatic like oscillation of the efferent arterial and that preferential non-enzymatic like oscillation of the efferent arterial is going to cause you to have a narrowed efferent arterial a subsequent higher climber capillary pressure and it increased amounts of GFR yeah the diabetic had increased GFR well if that stress continues for a prolonged period of time well guess what the response to cellular stress is going to be to hyper proliferate the mesangium but also after a while the stress is going to outweigh the compensatory mechanisms and actually we are going to have micro or even macro ow you min Maria and when you have micro or macro albuminuria that is going to kind of represent that there is some element of glomerular damage and that is probably due to the non enzymatic like oscillation of the efferent arteriole causing that back pressure and so a classic us Emily question if that if you see a diabetic with proton area and they have hypertension for example the best medication to use is ace inhibitors or ARB s and the reason why is because ACE inhibitors and AR B's reduce angiotensin ii concentrations and thus reduce the efferent constriction subsequently decreasing the glomerular capillary hydrostatic pressure okay very important and I want to integrate all of this in as we are preparing together very good all right so this slide is straight from BRS and what this basically tells us is that if you have increased efferent arteriole constriction you are going to have a higher oncotic pressure in d where peritubular capillaries there they are again and that higher oncotic pressure and the peritubular capillaries is actually going to cause us to reabsorb more water and reabsorb more ions the gradient is going to be more favoring for reabsorption that makes sense in a very stress state in an increased aldosterone state in a sympathetic state you want to actually hold on to things and it's all based on the fact that you squeezed a lot at the efferent arteriole now this goes back to our question with the NSAIDs and the NSAIDs remember reduce P G's prostaglandins and if NSAIDs reduced prostaglandins you get constriction of the afferent arteriole less blood going into the system you have less glomerular capillary hydrostatic pressure and you have decreased GFR and so on the USMLE whenever they have a patient who comes in and and in the vignette they say a patient with history of osteoarthritis I want you all to think in your mind hey make sure they're not testing me on the complications of NSAIDs complications of an said let's go kidney is one of them decreased efferent arteriole are kind of tone and you're going to have constriction of the efferent arteriole and subsequent decrease in renal blood flow second question that they can ask is going to be that hate NSAIDs affect platelet aggregation yeah and so it's affect platelet aggregation and so that could actually cause these patients to bleed a little bit more third question that they could ask is NSAIDs can cause a gastritis picture and that is because prostaglandins are very important in increasing the mucus that mucous layer of the gut and so when you have reduced prostaglandins reduce mucus layer acid can then win and you can have that irritation so as you can see from NSAIDs I kind of took all the different vignettes and kind of packaged them together for you because I want you all to learn in a clinical vignette based application mechanistic way that is very integrative all right very good excellent are you guys hanging in there let's let's get like a whoop-whoop or yes yes in the chat box all could yeah very good wonderful wonderful alright and those people who have their hands raised I will definitely answer all of your questions I will definitely answer all of your questions as soon as I'm done but yep perfect excellent excellent wonderful all right so continuing on a patient with diabetes a patient with diabetes is oh sorry about that a patient with diabetes is found to have a blood pressure at the outpatient visit of 145 over 94 so a little elevated he has started on in east inhibitor what effect would this have on glomerular hydrostatic pressure hmm ates inhibitor what effect would that have on chimera or hydrostatic pressure let's get a up or down in the chat box up or down and you guys are all understanding the concept yes yes yes very good decreased mechanism here is ace inhibitors inhibit angiotensin ii and that mediates the tonic control of the efferent arteriole very good excellent all right next concept we're gonna be talking about r22 okay what is going to be GFR and knowing renal plasma flow and renal blood flow now what is going to be the normal GFR well the normal GFR is about 120 MLS per minute you need to know that number like right off the top of that no but at least it gives you some context okay a patient is found to have a low GFR the medical student what an awesome medical student would like to manually calculate for his patient the GFR to impress the attending nice what is the ideal substance the medical student can use to measure this values hmm so the ideal substance to measure the GFR is actually going to be inulin yeah and the unique property of inulin the most ideal substance is that inulin is filtered but it is not reabsorbed or secreted it is the true marker of GFR because again it is filtered and nothing is touching it you're not taking it out or you're not putting anything back in and that means that the clearance of inulin clearance which is basically the urine concentration times the volume of urine over the plasma concentration the clearance of the inulin is equal to GFR okay very important for you to know now what segments of the nephron has the highest concentration of inulin and that is basically where there is less water because the less water in the lumen of the nephron is going to mean that there's a high concentration of inulin and where do we concentrate majority of our urine and a majority of inulin well yeah in the terminal collecting duct exactly in the terminal collecting duct remember those are aquaporins insert' and cause you to reabsorb more water now the segment of the nephron that has the lowest concentration of video actually is going to be in the Bowman's space there's no reabsorption of water and this is going to be filtrate that is going to have both water as well as inulin so clinically what we use to help us evaluate GFR is going to be creating exactly the clearance of creatinine is going to be the practical or the clinical marker we use now the unique property of creatinine is that creatinine is going to be filtered just like in Ulan but hey guess what there is some secretion whereas in Ulan there was no secretion but hey creatinine there is a little bit of secretion and so based on this we will kind of understand that creatine creatine is actually going to overestimate overestimate your GFR by about 10 percent creatinine's because there's a little bit secretion it overestimates your GFR by 10% next concept we're going to be talking about is going to be renal plasma flow now renal plasma flow is about 600 MLS per minute okay fine do you have to know that number memorize it yeah I don't know but guess what I first want to just talk to you from a he marked it what is plasma well right now if you kind of cut your skin and you saw the blood and from the blood it's like you were in a grocery store and you said let me take all our B C's let me take out WBC's let me even take out the platelets you would be left with the extracellular matrix of the blood and that is going to be plasma so plasma is the extracellular matrix of the blood there's no RBC's there's no WBC's and there are no platelets and what we understand is that plasma makes up about a little over half of the total blood volume of the body's total blood volume and remember on our first slide when we said the renal blood flow is about 25 percent of cardiac output remember we said we know blood flow is about 25 percent of cardiac output in this renal blood flow is about 1.1 right that's 21 percent or 25 percent of that 4.5 about 25% of that 4.5 liters per minute of cardiac output so that's where we got that one point one if you take one point one and you put fifty five or multiply it by 0.55 which is amount of plasma that's where we get the 600 from okay so is this going to be like tested like directly on there you only know but it's all conceptual right you understood that 25 percent of cardiac output is going to be renal blood flow well what percent of the blood is plasma about 55 so one point one times point five five well that's renal plasma flow okay excellent so a patient is found to have a low renal plasma flow the medical student would like to manually calculate this for his patient to impress the attending all right what is the ideal substance that we use to measure the renal plasma for hmm the ideal substance that we use to measure the renal pass plasma flow a lot of people are chiming in right now yes you got it that's going to be PAH and the unique property of PAH is that it is going to be filtered and secreted but not reabsorbed filtered and secreted but not reabsorbed nothing's taken out of it so what I want to kind of simplify for you and say in other words not all of the PAH crosses into the primary filtrate can you believe it well yeah some goes into that peritubular capillary system after the e friend a little bit of PAH goes into that peritubular capillary system and is subsequently secreted as you can see pah filtered and secreted now that means that the venous pah concentration is not zero right because I said it goes in the aether yes majority of it goes and gets filtered but then what about a little bit in the efferent yeah well there is a little bit in the efferent and subsequently in the venous system and what we recognize is that the venous pah concentration is about 10% of the arterial PAH and all I'm trying to tell you is that renal plasma flow if we use PAH because there's some unaccounted for PAH it is actually going to be underestimated okay so let's kind of synthesize all of this the high guru way right GFR the GFR is going to practically be measured by creatinine clearance creatinine filtered and secreted and because there is a little bit of secretion creatinine overestimates the GFR by 10% renal plasma flow is going to be the UV over P which is the clearance of PAH and remember PAH is freely filtered and secreted but there is some venous concentration and because there are some that is unaccounted for PAH clearance underestimates renal plasma flow by about 10% all right now what I'm going to be doing is giving you a little application question concerning the measurement of renal plasma flow and GFR which are the following are true I'm gonna take a nap 30 seconds I'm just gonna take a nap and you guys go through read the answer choices and type in the chat box type in the chat box what you think the answers you you you you you all right we got a lot of mixed answers yeah excellent well the answer is going to be e and this is directly from BRS physiology and essentially what I want you to recognize is that yes inulin is a good marker for GFR and that's because it is not reabsorbed or secreted by the renal tubules now as you go into the proximal tubules the fluid itself overall is I so osmotic the fluid itself is I so osmotic but remember your osmolarity is primarily defined by sodium concentration urea concentration as well as glucose concentration and so inulin concentration in particular as you are going to reabsorb water in the proximal convoluted tubule the inulin concentration increases progressively okay and that's because yes the fluid itself is also osmotic but if inulin necessarily doesn't play into the osmolarity of a fluid pah is a good marker of renal plasma flow we talked about that it is freely filtered and a very little pah reaches a renal vein and that's why we say it underestimates renal plasma flow by about 10% okay awesome so we're learning some good facts and we're gonna continue on with our review and talk about renal blood flow now the relationship between renal plasma flow and renal blood flow is the following well renal blood flow is going to be B the equation for renal blood flow is going to be renal plasma flow divided by 1 minus hematocrit how I kind of just remember this is I say hey renal blood flow well renal plasma flow is the plasma is basically blood without all of the different stuff so 1 minus hematocrit kind of adds all that stuff back in so renal blood flow is renal plasma flow over 1 minus somatic read just add all that RBC is platelets WBC is that we took out for making plasma now this is extremely important for your step one and that is going to be the relationship between renal plasma flow as well as GFR now renal plasma flow and GFR the relationship is best described by the filtration fraction we're going to have an application question that the USMLE can test but I want you to know that GFR / renal plasma flow is a filtration fraction don't memorize please understand with me of the plasma that comes to the kidney or of the plasma that comes to the glomerulus how much of it is filter let's say that again the filter a fraction is a fraction of what comes in Reno plasma flow that is filtered across the glomerular capillaries so basically what comes in what percent of that is going to be kind of filtered out so filtration fraction extremely important concept and as we can see the normal filtration fraction is 20 ooh 20% all right let me take out my iPhone real quick GFR was 120 right and the renal plasma flow so can I just say it right here GFR / renal plasma flow GFR 120 MLS per minute I was like don't memorize it you guys all memorized it and renal plasma flow is about 600 ml per minute 120 divided by 600 so 120 divided by 600 is equal to 0.2 so that's where we get the filtration fraction being 20% and so what happens to be remaining 80% well it becomes that peritubular capillary system because that's the stuff that is not filtered across but continues in the efferent and subsequently through the peritubular capillary system so let's go through this a patient with low blood pressure he's found to have activation of rass what effect does this have on peri tubular oncotic pressure guys stay active and engaged what do you guys think up or down answer this question we have so many people in this room it's busting open today all right Shubham awesome remember activation of wrasse I'm getting some decreases you answer is going to be actually increases let's go through this okay okay I can't just sit here and read you first date I'd be doing you a disservice if I just end up leaning your way without application Riya no plugs no I'd be doing you a disservice let's go through this a fare Club Mary Alice efferent grass remember constricts that efferent a little bit more than the apron preferential constriction right angiotensin 2 and you squeeze more GFR out more fluid out and in the peritubular capillary system because you squeezed all that fluid out the oncotic pressure the pulling pressure is going to increase and that's why in that state you're reabsorbing more very important concept and the explanation is that increased peritubular capillary oncotic pressure downstream is going to translate to increase proximal tubular reabsorption okay because it's a more pulling gradient very good excellent excellent and this just says efferent arteriole and then peritubular capillaries here we have an old man who presents with flank pain and he mature anytime I see flank pain and microscopic hematuria flank pain plus microscopic hematuria I am particularly thinking about nefra latias asan the USMLE exactly stone very good Shuba on CT is found to have dilation of the right your etre representing obstruction what effect will this have on GFR renal plasma flow as well as filtration fraction so i will go through and answer this question for you as you can see this is going to be the kidney and the glomerulus is within the kidney there's a stone right here and that is causing a lot of back pressure now that back pressure is going to decrease our GFR again if we look at the glomerulus the true the true explanation is we have increased static pressure of the interstitial fluid or of the Bowman's space same thing increased hydrostatic pressure of the interstitial fluid or the Bowman's space and that is because of the obstruction the post renal obstruction that we have now typically this doesn't change your renal plasma flow until much later if you have much severe damage then you're going to actually change your renal plasma flow but if you decrease your GFR and you basically at this point don't change your renal plasma flow the cont the kind of concept that I'm going to be illustrating to you is that you have a decrease filtration fraction and that's because of this whole paradigm okay so as you get the actual intra renal damage yes your renal plasma flow can decrease but the whole notion is is that because you increase the hydrostatic pressure of the Bowman's space you are going to be getting a reduced GFR all right excellent next concept that I want to illustrate to you is going to be the concept of splay and glucose urea very good obese woman is found to be diabetic her fasting glucose is 253 what will a urine dipstick likely show well the concept that I'm trying to go for here is that if you have an elevated very elevated serum glucose your serum glucose he is going to actually start spilling into the filtrate ie the urine dipstick can show trace glucose urea and the essential physiologic concept that explains this phenomena is going to be display now the mechanism here for splay is kind of twofold number one number one why do you have splay why do you have splay look at a chart but the reason you have splay is because you have this low affinity of sodium and glucose co-transporter they're kind of transiently attached thus near your transport maximum of glucose which basically means the transport maximum is going to be that threshold in which glucose can no longer no longer be pulled back into the body from the urine near TM of glucose essentially here is this transient kind of affinity and excreted into the urine because there are few remaining binding sites where it may reattach okay so that low affinity and the fact that as you go towards the TM both of these contribute display now secondarily secondarily the heterogeneity of nephrons the fact that all nephrons are not created equal also is going to be a mechanism behind splay and so as we recognize that the TM for glucose is going to be essentially reflective of the whole kidney and that whole kidney transport maximum is basically the average of all of the nephrons so some now front will reach TM and give you glucose urea very quickly well very quickly whereas some take a little bit longer so twofold concept affinity for the sodium glucose transporter as well as the heterogeneity of the nephrons and this is going to be from your boron and bo-peep big physiology textbook but essentially we see on the x-axis this is how I like to tell you to answer all us MLA questions on the x-axis you want to orient yourself this is plasma glucose and on the y-axis you have filtered load reabsorption or even excretion but basically has all these concepts that we talked about of glomerular physiology at this threshold of about 200 you start having threshold of 200 serum glucose you start having some glucose that starts going into the P and at this threshold we try to say that the filtration is equal to reabsorption the amount of glucose that is filtered he is going to be reabsorbed but but as we start increasing from that 200 number well yeah if we get to 250 to 350 we are going to be in this gray zone that we talked about called splay in which you likely will have a little bit of glucose urea and as the serum concentration of glucose increases you will eventually eventually reach TN and TN which is around 350 serum glucose your filtration is going to just outweigh your reabsorption that means what that glucose is going to be filtered but man we don't have enough nephrons and we don't have enough affinity and binding sites for the glucose to be reabsorbed and so splay is this concept in which there's that gray zone 50 shades of gray there's that gray zone between 250 serum glucose and 350 serum glucose in which you can start seeing some glucose in the pee what are questions that they can ask us Emily first question that they can ask on this is the child who comes in with a new diagnosis of DKA has a high serum glucose and they'll ask you hmm what's the mechanism as to why these this patient has glucose urea on the dipstick and that's say the answer is the same stuff we were talking about second question that they can ask is they can have a kiddo who has for example obesity a kiddo who has a camp dosis nigricans metabolic syndrome and they say man he keeps wetting the bed and when he wets the bed they check a glucose in the serum glucose says for example 300 if they check a urine on that kiddo guess what the urine will show glucose urea why because you are kind of in that splays own in which you are going to have glucose urea okay or the the potential to having glucose urea because your serum glucose is so high all right everybody well everybody has been sticking around so far and our last thing before we stop this presentation today our last thing is going to be going through the nephron we're gonna take a nice little trip to the nephron so are you pumped for a field trip everybody in the chat type in I'm pumped I'm pumped let's get it yeah awesome excellent we have so many people that are participating that's great we have so many more people come on I need a couple more I'm pumped if you haven't typed it in yeah Tina got it all right awesome let's not excellent excellent we got a lot of people here today so I appreciate everybody's participation excellent wonderful wonderful pump like the heart all right so let's start with the proximal convoluted tubule okay now in the proximal convoluted tubule here are the key USMLE points DUS Emily points ready majority of sodium reabsorb at the proximal convoluted tubule that's point number one point number two what you have to know is that the sodium reabsorption is coupled to the transport of other things such as glucose amino acids lactic acid okay or lactate as well as different ions okay the transport of sodium is coupled to all of these ions okay now two questions that they can ask this is going to be an example of secondary active transport and that's how you'll for you to know that this is an example of secondary active transport because we are using this basal lateral sodium potassium ATPase to drive the reabsorption of the other ions second question is that if you cannot reabsorb all of these ions the question that they can ask is what is the pathology and that is Finco knee syndrome now think Coney syndrome can be due to toxins can be genetically mediated and faint Coney syndrome is basically when you cannot reabsorb anything from the proximal convoluted tubules now what affects the sympathetic nervous system have on the proximal convoluted tubule well the sympathetic nervous system up regulates the sodium potassium ATPase and it enhances the fraction of sodium reabsorption and that makes sense because you are going to need more to be coming in as you understand about water chloride and K are going to actually be reabsorbed here as well and k and cl actually are going to be reabsorbed via what we call a pair of cellular transport in which it is between the renal proximal convoluted tubule epithelial cells now the majority of the filtrate that is filtered and reabsorbed what do you think by the end of the proximal convoluted tubule what do you think is it are we high paws monic hyperosmotic or iso osmotic and I don't actually gave this answer already but let's see if you are listening majority of this Phil Tree is a hypo hyper or ISIL getting a lot of ISOs excellent very good guys wonderful all right and so the majority of the fluid by the end of the proximal convoluted tubule is ISO osmotic and that is high-yield for you to know that it is iso osmotic continuing on let's go through a USMLE question a patient with diabetes is going to be on a new drug and this new drug affects the proximal convoluted tubule what is the likely mechanism of the drug hmm so diabetes what we are going to see in diabetes is that we need to reduce sugar concentrations right how do we reduce sugar concentrations and related to nephrology well you pee out the sugar oh my gosh there is a medicine that can help us pee out the sugar yeah exactly it's going to be the sglt2 inhibitors okay and the sglt2 inhibitors make us pee out the sugar and thus reduce our serum glucose levels in diabetes the sglt2 inhibitors all end in frozen canagliflozin for example are invokana okay that's the brand name but canagliflozin everything flows in and so canagliflozin czar all the flows ins inhibit sglt2 and sglt2 is actually a transporter a sodium glucose transporter that is going to be in the nephron at the proximal convoluted tubules so that's very high yield for you to know and this is how physiology relates to pharmacology on the step one now high yield for you to recognize is that with these flows and medications a very common side effect and relative contraindication is the risk of UTIs remember if you are going to be glucose uremic ie are going to be peeing glucose out nakkeera is gonna love that and when bacteria loves it you got it you can have a predisposition of infection lastly I want to let you know that bicarbonate is going to be reabsorbed in the proximal convoluted tubule via a luminal carbonic anhydrase in the intracellular carbonic anhydrase as you can see this luminal carbonic anhydrase takes bicarb that is in the tubular fluid and the luminal carbonic anhydrase is going to do its thing and do its reaction and cause us to make carbon dioxide this carbon dioxide is going to go and get affected by the intracellular carbonic anhydrase and this carbon dioxide plus water actually is going to restart the cycle of us reabsorbing bicarb ie it is going to take the H+ and that goes into the tubular fluid such that it can it can actually give us one more bicarb reabsorb in this area right here represents the fact that you re absorbing the bicarb in the peritubular system okay and so the fact that the USMLE can test is that if you have the reabsorption of bicarb in the proximal convoluted tubule it is the filtered bicarb that you are going to be reabsorbing and that is due to a luminal carbonic anhydrase as well as a intracellular carbonic anhydrase second thing that you have to know is that there is a medication which actually inhibits ooh inhibits this luminal carbonic anhydrase and this luminal carbonic anhydrase is going to be inhibited by acetazolamide and acetazolamide is going to cause you to pee out your bicarb and subsequently water with it that's why it's a diuretic and acetazolamide how I like to think of it it takes a seat it takes a seat on carbonic anhydrase okay all right very good next area we're going to be talking about is that loop of Henle now remember that the descending limb of the loop of Henle is going to be very permeable to water and i think of it as waterfall so the descending limb of the loop of Henle is very permeable to water whereas the big ascending limb that thick ascending limb okay that is going to be where a lot of the action of solutes solutes are going to be coming out like electrolytes okay one particular transfer that you must go into the USMLE knowing is the sodium potassium to chloride transporter and the sodium potassium to chloride transporter high-yield for you to know is going to be inhibited by loop diuretics and loop diuretics or things like furosemide torse amide and at the critic acid and that's USMLE questions for you to know now loop diuretics are going to be known as furiosa my tour cement and at the clinic acid and it inhibits the sodium potassium to chloride transporter in the thick ascending limb of the loop of Henle okay this is the diuretic that we use in the clinical setting when we want to get fluid off really quickly we use lasix which is furiosa bide we use a very quick and that takes a lot of fluid out makes you pee out so in a patient was heart failure for example who is very fluid overloaded we're gonna use the diuretic furosemide for the relief of the fluid overload okay and so descending limb permeable to water he's sending limb permeable more to solutes think about this important transporter alright next area that we're gonna be talking about is the distal tubule you're like I'm really tired right now I'm really tired well come on get energized get energized right we're gonna be almost done after we talked about the distal tubule and the collecting duct and then bye bye see ya right now I'm just kidding so distal tubules distal tubule what we have to recognize is that there is an important sodium chloride symporter in the distal convoluted tubule the symporter which is the sodium chloride symporter that is actually inhibited by thiazide and the name for thiazide is basically hydrochlorothiazide hydrochlorothiazide inhibits the sodium chloride symporter now can I make a little riddle for you furosemide is to be a sanding loop of Henle as thiazide x' are to the distal convoluted tubule furosemide diuretics inhibit the sodium potassium to chloride transporter whereas thiazide diuretics inhibit the sodium chloride symporter the pair law the compare and contrast that's how you study that's how you promote memory and so this section is impermeable to water you're pulling out more solutes and that's why your Oslo allottee actually decreases even further because you're pulling out so much solute in fact a little fun fact the distal convoluted tubule has the lowest osmolarity of the entire nephron and that's high-yield now one other concept that I just want to illustrate right here is the fact that parathyroid hormone parathyroid hormone parathyroid hormone actually acts at the distal convoluted tubules so this is a good endocrine tie-in for your step one is that if they ask you what is the mechanism by which parathyroid hormone increases the calcium reabsorption well yes it has an effect on the proximal convoluted tubule because a lot of electrolytes are reabsorbed such as calcium at the proximal convoluted tubule however parathyroid hormone primarily affects the distal convoluted tubule and causes you to reabsorb that calcium okay at the distal convoluted tubule that's high yield for you to know okay all right excellent next area we are going to be talking about is the collecting duct we are almost done we are almost done and there are two cells in the collecting duct okay two cells and that is going to be the principal cells as well as the intercalated cells okay now the first thing that I want you to know is that principle cells are all related to aldosterone ADH and subsequently aquaporins whereas intercalated cells they're all about acid so let's start with the principal cells the principal cells are going to be controlled or be affected by the principles those affected by aldosterone okay now aldosterone is going to cause you to upregulate emac channels and the u.s. Emily really likes to know that that what is the mechanism for the reabsorption of the sodium okay the reabsorption of the sodium is going to be via aldosterone promoting emac channels to be inserted into the lumen of the principal cells such that you reabsorb the sodium very high yield for you to know now a patient has an aldosterone secreting tumor what effect does this have on principal cells well I just gave you the answer and that is the up regulation of the enact channels via the principles now why don't we answer this what effect does ADH have on the principal cells why don't you guys put that in and I'll answer your guys's questions soon but why don't you guys put that in what does ATH do to the principal cells what does ADH do insertion of what what protein what do you guys think yes people aren't putting it in yes very good Sarah excellent yeah be confident yes wonderful so yes you have the insertion of the aquaporins so aldosterone causes increased Enoch whereas the ADH causes the increase of aquaporins aquaporins all related to water the receptor that ADH acts on a receptor the ADH acts on again this is us Emily first aid endocrine I'm not biessing you here the receptor is going to be the v2 receptor and the v2 receptor is going to be the receptor ETH axon in the principal's house and the v2 act by a GS pathway now a biochemistry integration for you what amino acid is the precursor for a th and that is gonna be our journey Argentina is the amino acid that is a precursor for ADH all step one integrative question based active recall that is the name of the game ladies and gentlemen so why don't we why don't we go on to this question right here okay and I want you all to take 30 seconds and answer this question so within eight hours following large intravenous aldosterone infusion which are the following are clinically evident alright wonderful why don't you think about this and just to give you a time check we're gonna be done in just about less than 10 minutes so wanted to let you all know that thanks for sticking around so go ahead all right I need more people to answer I need more people to answer you have about 50 people in this room come on all right yeah awesome wonderful and the answer is going to be C ladies and gentlemen please know that if you know aldosterone if you know aldosterone if you know aldosterone and the renin-angiotensin-aldosterone system you will do so well on your step one why it's an important concept there are many questions that are derived from this well let's go through it ready aldosterone aldosterone brings in the sodium from the urine it brings in your sodium and what does it make you pee out potassium and hydrogen ions whoo whoo gotta know this wait so you're telling me hmm you're telling me if I have an aldosterone secreting tumor I am hibernate Tremec hi oh-kay lemic and I have a metabolic alkalosis yes you're absolutely correct in cases of primary hyperaldosteronism on your step one this is going to be a patient who has what we call Conn's syndrome constant impatient s' there hyponatremic there hypertensive because with the sodium comes the water and there hypokalemic and metabolic alkalosis very important for you to know well what about if you have how about this the other opposite adrenal insufficiency say you have for example the severe form water house free grits in syndrome USMLE TYIN Neisseria gonorrhea hemorrhagic infarct of the adrenal glands or say you have Addison's disease Addison's disease USMLE yes exactly Addison's disease is when you have primary hypo aldosterone ism and in this case you're gonna be hyponatremic you're gonna have a low blood pressure and you're gonna be hyperkalemic with a non Anaya gap metabolic acidosis so here we go states of aldo excess is going to cause you to have eight metabolic alkalosis wife because you're peeing out a lot of h+ states of aldosterone and low metabolic acidosis and because i'm all about the details non anion gap this is how nephrology relates to acid-base okay excellent so just finishing up here what i want you to know is that here we have the intercalated cells the intercalated cells is going to deal with acid remember principal aquaporins ELAC right whereas intercalated they're all about acid and this is in the collecting duct as you see we do not have we do not have a luminal luminal carbonic anhydrase the luminal carbonic anhydrase was in the proximal convoluted tubule here here we have a chrysella carbonic anhydrase and this intracellular carbonic anhydrase makes you pee out your excess acid makes you pee out your excess acid and we have buffers in our body h2 po4 ammonium from the kind of correlated to the urea cycle but these are going to be mechanisms as to how we buffer the H+ and so if I ask you what role does aldosterone have on the Alpha intercalated cells what role does the alpha aldosterone have on Alpha intercalated does it up regulate them or down regulate them what do you think guys does Alpha intercalated cells what does it do and people are so right when they say up regular yeah remember it is going to up regulate the HTTP remember out Doster brings in sodium and makes you pee out potassium and makes you pee out hydrogen ions and the up regulation of the HTTP is the mechanism aldosterone increases the HTTP so in summary intercalated cells are all about acid-base regulation while ladies and gentlemen guess what we did it we went through the whole nephron starting from proximal convoluted tubule to the collecting duct I want to thank you so much for joining me today on this with this review okay please stick around for just a second because I want to end on a very positive note okay and I want you to recognize that your positive action combined with positive thinking is going to result in success and I'm so humbled by you all joining and a very very very special announcement is that next weekend I'm actually going to be doing a webinar and it's going to be next Sunday and what we're going to be doing is we are going to actually be reviewing the top miss concepts basically what I did I went through all of the question things and I figured out what are the hardest topics from the question banks as well as the USMLE content outline and we're going to review the most difficult and most miss concepts from each organ system we're gonna get the hi guru notes when you register and it is going to be next Sunday bright and early 8:30 a.m. it's gonna be for three and a half hours I'm actually running a special as I teach many USMLE classes I usually charge 98 dollars for this session however I encourage you all to sign up and for you guys joining today the registration fee is 65 I'm gonna email you the link but right now I'm just gonna copy paste it into the chat box right here and feel free to click on the link and register today I'm only going to be keeping at a very small classroom not this big webinar style but just a really intimate group of students I've been humbled you know last last week we had a rapid review session and we got so many good testimonials from that rapid review session so you know today I the one asked that I have is you know first off just stay positive in your step 1 preparation if you have any questions definitely reach out to me connect with me on social media a month Twitter Facebook Instagram I have daily USMLE questions that come out and I just want you all to recognize that yes it's a very stressful time but if you just take actionable steps and you apply yourself you apply the content you will do really really well so feel free to definitely write a review that would mean so much to me let me actually type in the link where you can write the review on Facebook that would be so awesome if you can unfortunately I have a question from somebody can we get today's webinar video recording actually due to copyright we are not going to be sharing this video recording however if something changes I'm definitely going to let you know but I just wanted to answer that question if you all have any questions please stick around now and type in the chat box otherwise you all are free to go thank you so much for joining and I'm gonna stick around and answer any of the questions okay but thank you George thanks so much for attending all right awesome we have so many people they're just exiting if you have any questions definitely let me know okay all right