Tubulointerstitial Disease | Clinical Medicine

what's up Ninja nerds in this video today we're going to be talking about tubulo interstitial diseases that includes ATN which is a tubul necrosis a in acute intertial nefritis as well as renal papillary necrosis again this is part of our clinical medicine section if you guys like these videos they make sense they help you please support us you can do that by hitting the like button commenting down the comment section or subscribing all right also and I really think this would benefit you down in the description box below there's a link that goes to our

website on our website we have a lot of Premium resources we have notes we have illustrations we got quiz questions we even have case series on certain topics so go ahead and check that out and I think that you'll benefit a lot without further Ado let's talk about tub interstitial diseases all right so let's talk about the pathophysiology of these diseases it's really important to kind of have an understanding of these we talk about um actually these two particularly in Ute kidney andury and that's really an important area to understand their significance I just think

it also deserves a potential you know a little bit more talk about these diseases on its own but again do remember that acute tubular necrosis and acute intercal nefritis are very common causes of what we call intrarenal Aki all right with acute Tu necrosis being like most often that costs like 80 to 85% of the time so when we talk about these it is important to really talk about these in the concept of knowing that these are underlying causes of acute kidney injury and the renal papillary necrosis can also cause cause Aki and so it's

a possible discussion there but I wouldn't put all your eggs in that basket I would focus on this as kind of one of those very interesting Niche talks about uh you know underlying kidney diseases and that's where renal papillary necrosis belongs is in the concepts of like these little niche areas such as hematuria and even potentially like infections like pylon nefritis but we'll get into each one of these and and we'll talk about them I just want you to understand the importance of these is that these are really heavily discussed more in Aki that one's

kind of a little niche area but we'll give a little bit of discussion on it all right acute tubular necrosis concept of this is that you're causing necrosis of the proximal convoluted tubular cells it can involveed other different tubular cells but I'd say the most majority of the area of the nefron is going to be the proximal convolutive tubal now the concept behind this is that what happens is there's usually two underlying mechanisms one's esea one's nephrotoxic mediated now in eskee the concept here is that there is a reduction we'll say in what's called renal

perfusion and there's a lot of different reasons why a patient can have reduced renal profusion often times it's just a very low blood pressure so scenarios of hypotension or shock is a very very common one and we'll talk about those um but what happens is when a patient has prolonged you know reduced renal perfusion or renal hypo profusion one thing that can happen is you'll have a hard time being able to filter as much blood across so that'll lead to a reduction in GFR but the big thing here is that the AER arterial who receives

blood feeds it into Glarus it should leave the Glarus via the eer arterial and then run down through these little things called the peritubular capillaries and guess what these are supposed to do they're supposed to supply oxygen to what to the tissues of the proximal convoluted tubal the distal conv tual all of those different areas now if for some reason you have a reduction of renal profusion you're going to reduce the oxygen delivery to these tissues whenever you reduce oxygen delivery to these tissues and it's not reversed it's not reversed what's going to happen is

these tissues will start to undergo es schea and as they undergo esema if it's not reversed properly these tissue cells will undergo necrosis and they will die as they die some of these tissue cells kind of sloth off so imagine it's epithelial tissue they start to kind of like literally wither away and they sloth off into this Lumin of the proximal tubule when they do that now what happens is these like epithelial cells they kind of like clog up this highway they clog up the actual tubular Lo in the problem with that is is that

you want to filter things across here but it doesn't allow you to and so what happens is this starts causing like as the filtrate starting to filter it literally causes this to build up and when it builds up proximal to this area right what's going to happen is this is going to cause the pressure pressure inside of the Bowman's capsule to go up and so what we call that is whenever there's a pressure in here that increases we say there's an increase in what's called capsular hydrostatic pressure so capsular hydrostatic pressure that is going to

increase when that increases what it does is is it actually leads to a difficulty in allowing for fil treate to cross the Glarus and go into the Bowman's capsule and that's glome filtration rate and so what happens is a result of this is that these patients experience kind of a reduction in their filtration process because of this backup and so what this does is this actually drops the patients GFR their glomular filteration rate and that will lead to especially if it's Rapid or abrupt it'll lead to an acute kidney injury and so that's one of

the concepts that I want you to understand here is that one of the reasons why patients develop aute necrosis is that they have reduced oxygen delivery from reduced renal profusion and usually for prong per periods of time the other common cause here for these patients is that it could be nephrotoxic induced in other words there's a maybe there's some type of like medication of sorts and you become exposed to it and what happens is some of it gets filtered and you can excrete that drug but some of it continues to stay within the bloodstream and

maybe this drug has the C you know the capability per se to get taken up by these epithelial cells and whenever this drug gets taken up or these particular molecules get taken up by these peritubular cells these contain the capacity or the intrinsic ability to cause destruction of these tissue cells and so nephrotoxicity in this particular scenario could be due to multiple different things it could be due to drugs it could be due to um other different types of pigments it could be du to Crystal formation there's a lot of different things that we'll talk

about with respect to these NE toxins all right so the two big Concepts here is that it could be aeia that's leading to poor oxygen delivery or it could be a nephrotoxic substance that's causing tubular cell death either way in both of these scenarios the tubular cells SLO off and they plug up this Lumen if they plug up the Lumen it leads to a back pressure and what is that back pressure again called it's called capsular hydrostatic pressure that goes up and as the capsular hydrostatic pressure goes up here it imp feeds the flow of

filtrate out of the Glarus so you have an increase in capsule hydrostatic pressure that causes a decrease and the ability to filter things across the glamar it's called a GFR right and so this is what causes these patients to develop acute kidney injuries because this is usually a rapid reduction in GFR and then that causes an acute rise and their serum creatin going to drop off in their urine output all right so we have an understanding now of acute tub necrosis this is going to be one of the most important tubo interstitial diseases to be

able to identify the next one is acute inal nefritis I like to think about this as an allergic reaction essentially there's some type of exposure all right we're going to call this exposure we're just going to say it's an antigen and this could be a lot of different things if you will but we have an antigen exposure right maybe that's a drug maybe it's an infection maybe it's an underlying inflammatory response from an autoimmune disease whatever it is these patients become exposed to this antigen and it gets into the bloodstream when this antigen gets into

the bloodstream it maybe does not have exactly per se a amog potential let's say in other words it wouldn't be able to activate the immune system but if we go ahead and we connect this to a little molecule here maybe we bind on to this A protein that protein when bound with the antigen now forms something called a hapton and so now you have something called a hapton now hapton are highly immunogenic meaning that our immune system would identify this antigen and protein complex and say oh what this is and when it sees that the

problem with this is it's going to go ahead and say okay I'm going to bring my macrofagos to here and it's going to go ahead and phagocytose this and so it's going to undergo a phagocytosis mechanism when this phagocytosis mechanism occurs what you're going to see here is it's going to take up this hapton and maybe Express a piece of it on its mhc2 complex and so this macras will then say okay or this antigen presenting cell will say okay let me present this to a T cell when it presents this to the t- cell

via its T Cell receptor and connecting with the mhc2 complex this creates an interaction if you will this interaction causes hyper stimulation of the te- cells and what these tea cells start to do is they start to release a bunch of cyto kindes it's going to release a ton of different cyto kindes but I think some of the cyto kindes that are actually potentially worth me remembering are cyto kindes there's a couple of them but I'm going to put one big one includes interlan 5 what you may know about interlukin 5 is this has a

very strong effect on eosinophils eosinophils love this cocine and so what happens is these cyto kindes come and stimulate these eosinophils and this is particularly occurring a lot in the kind of renal interstitium area so here between the cells and the blood vessels and so this is going to activate these eosinophils and now you're going to have all of these eosinophils who are going to kind of be hyper stimulated and there's going to be other immune system cells that's not just the ashil but you're going to really stimulate these to go and infiltrate into this

tubular interstitial area and what they're going to do is is is they're going to start kind of accumulating all here and they're going to release more cyto kindes and there's going to be lots and lots of inflammation here so there's going to be tons and tons and tons of inflammation let's represent this with like this blue color and so now you're going to have all of this inflammation that's occurring around this area here with all of this cellular infiltrate what's going to happen is all this inflammation and edema in the interstitial area is going to

start having a mass effect and what it's going to do is it's going to start compressing on the tubules look at this tubule and look at this tubule you see how much like more narrow this one is so you get a compression of the tubules all right so this increasing edema will cause tubal compression and what that'll do is is it'll make it harder for this filtrate that's being filtered off to run down it's going to be kind of obstructed there and what that's going to do is as blood kind of comes into the Glarus

is going to be harder for it to filter if this is building up and again this tubal compression is going to lead to an increase in the Glam the capsular hydrostatic pressure which will drop off the patient's GFR so you're going to see an increase in the capsu hydrostatic pressure which will drop off the patient's GFR so it's a similar concept when you really think about it in the sense that something is obstructing that flow you can't get things down here and it was the same for acute tubular necrosis the difference is that you had

cells that were blocking up the Lumin here there's a lot of Edema and that edema is really what's causing compression and external compression of the tubules and if I'm stimulating this increased tubal compression that's what's going to drive down my GFR and cause an acute kidney injury so that's a concept that I really want you to understand here is that they're going to have a lot of Edema and an inflammatory infiltrates with eosinophils other white blood cells but this is the real big one here and often times it's some type of antigen that's triggering this

process that's the big thing to remember here guys all right so we have a Q necrosis all right I kind of got an idea esea nephrotoxins okay cool not too bad I know the primary mechanism behind it is that the dead cells are blocking up the tubular Lumen acute interal nefritis is an antigen exposure that's causing a type four hypers sensitivity reaction which is a t- cell mediated inflammatory reaction that's causing a lot of EMA inflammatory infiltrate compressing the tubules and knocking off that GFR the last one is a little bit more kind of different

all right and it's called renal papillary necrosis the concept behind this the primary mechanism is usually the patients are experiencing enough renal esea so in other words they're not having enough blood flow to their kidneys you're like Zach wouldn't that be acut necrosis in a way it it's just a slightly bit different with a qal necrosis the primary problem is you're not profusing the Glarus and getting the actual kind of the cortex areas those tubular cells are getting necrotic with renal papillary necrosis the most common area to be affected is when you look at the

kidney here you see these area these kind of like triangles here these particular areas these are called your renal pill so you have these things called your renal pyramids if you guys go back to your Anatomy these are your renal pyramids and then up here would be the cortex and then down here would be the Pilla this is the area that is the most prone to causing necros undergoing necrosis so what I want to do is I want to take this area and I want to zoom in on it and take a better look at

it so let me explain something the concept behind here is that you have blood flow coming up through this area and then here at the pill you have these tight little blood vessels called the vasera if there is not enough renal profusion maybe there's an obstruction of the vessel maybe something is compressing The Vessel but whatever it is I'm just not getting enough oxygen delivery to these tissues that's going to cause the same exact concept that we talked about before so you're going to have a renal blood flow here but you have to look at

this a little bit differently as renal blood flow is coming in via the vasera if there is some particular reason as to why we are not dropping off oxygen there is a decreased oxygen delivery then what's going to happen is this tissue is going to start to undergo es schea and as it starts to undergo es schea it will start to die and so what will happen is this patient will undergo what's called papillary esema esia so they'll undergo papillary esea that then if not treated will lead to papillary necrosis so then that's what we

have to think about is what's actually causing this reduction of oxygen delivery to the renal pill that's really the question that comes about here because the problem with this is if this tissue starts to die imagine all of this tissue here dies guess what can happen if this tissue dies it can literally kind of sloth off here such a weird word sloth it could sloth off into the actual oral cix and then get guess what this tissue which I'm going to kind of represent here in Black could get stuck it could literally get stuck in

the Mur and create an obstruction this can cause urinary stasis proximal to that and cause increased risk of infection it can block off the filtrate and lead to an Aki so this is definitely something of why we would want to be careful about this one so now at this point what I've left you guys with is that we have three tubular interstitial diseases to talk about ATN Ain renal papillar necrosis all of them are slightly different pathopysiology what I need you to start asking is what's causing this particular disease all right so let's talk about

the cause causes of each one of these tubular interstitial diseases so when we talk about a q tubular necrosis we know that there's primarily aeia related and the nephrotoxic mediated either way there's death death of these tubular cells there causing these kind of cells to get blocked up within the tubular Lumen increase the pressure inside of the tubular system in the capsule which reduces the net filtration right that's the concept here the thing that you have to start asking yourself is what's causing that reduced renal profusion what are those nephrotoxic medications and so often times

es schic causes that lead to reduce renal profusion can come down to this diagram here let's say that a patient has cardiogenic shock if they have cardiogenic shock where maybe they had an MI maybe they have acute heart failure and in this scenario they have disease of their pump the problem is with their pump and so now their ability to get blood out of the heart is impeded so that's one potential mechanism right is really prolonged cardiogenic shock the next concept is let's say that the heart is pumping well but maybe the blood vessels are

super vasodilated so there's disease of the vessels so maybe here I have some type of disease process of the vessels and what's happening here is that maybe they're super super dilated because in this one it's reduction in cardiac output right that's the primary mechanism here here it's that it's vasod dilated and often times this is an example of what we call septic shock and usually this is a reduction in the systemic vascular resistance where the vessels are just super super dilated right that could also drop the blood pressure so both of these this reduction of

cardiac output leads to reduction in map decrease in svr leads to a decrease in map the next thing is what if the vessels are underfilled what if you don't have enough blood volume in them and so the other concept here that you have to be able to ask yourself is what if the circulation is not properly filled and so when I look at this I'm not having enough blood volume to fill the actual vessel and deliver oxygen and nutrients to the tissue so that would be another potential scenario here so it could be cardiogenic shock

septic shock the last thing is what if it's hypo volemic shock or hypovolemia so hypo Valic shock and in this particular situation the blood volume is the problem and if you have a reduction in blood volume you will lead to a reduction in the indolic volume the preload the contractility um and then the cardiac output I'm sorry the they're pre-load and then the cardiac output so this is also going to drop their blood pressure either way in all of these scenarios the problem that exists here is that you're not profusing these kidneys and if you're

not giving oxygen to the tissue right what is going to happen it will then undergo es schea and when it underg goes aeia this will lead to acute tubul necrosis if it is not fixed so if we don't reverse that cause all right if it's prolonged that's really the the case here if it is prolonged low blood pressure this will lead to necrosis of the tissue all right and so that's the big difference here that I want you guys to understand so what you have to look for in these patients is is is there any

history of low blood pressure so you need to assess the big thing here is you need to assess for hypotension so assess for a decreased blood pressure right that's one really big thing but also look for other features of poor profusion so modeled skin you know and uh cold extremities also I would look for potentially elevated lactate levels that suggest poor organ profusion so a lot of these things could suggest that being the likely cause but often times it's just looking at their history to find what's really going on with the patient that would suggest

oh this is es schic related rather than nephrotoxin mediated the next thing that I would also want you guys to think about for these patients is if I have a patient coming in with an acute kidney injury right and I think it could be ATM and I don't really have any history that suggests that their blood pressure has been really low that they don't have any parameters of poor organ profusion then I would start thinking about have they had had any exposure to nephrotoxins drugs are the often the first thing that I'll go to the

history on and I'll look through their medication history I'll look for some classic drugs aminoglycosides tend to be a really big offender so this is an antibiotic um cisplatin which can be used as kind of a cancer agent a chemotherapy agent um another one could be OTAs so I like to think about this one is otable which is used in fungal infections usually systemic fungal infections the big one that I would want to watch out for is iodinated contrast and this is a really big one we talked about this in acute kidney injury we talked

about this in chronic kidney disease that contrast induc nephropathy is something that you have to be careful for with iated contrast it can do two things one is it can cause Vaso constriction so it can Vaso constrict the aarant arterial right so if I Vaso constrict this puppy here right it's going to make it harder for blood to get in to the Glarus right and that'll reduce the filtration but it'll also make it harder for me to give the actual blood flow to these tubular cells and so there will be a reduction in oxygen kind

of inadvertently here all right and that can cause some death to these cells the other concept here is that this this iated contrast may just have nephrotoxic proper properties and so it's also important to remember that this drug could just directly without having any kind of problems with esea could also lead to nephrotoxicity and so the concept here is that it may cause increased vas of constriction of the aperin arterial reduce blood flow via the Glarus and also just stimulate direct nephrotoxic Activity one of the big things here that we always talk about here is

you can try to prevent this by giving IV fluids to the patient pre and post contrast Administration so when a patient gets the contrast before that give them fluids and then post contrast delivery give them fluids that may help to reduce the risk of causing ATN and leading to a nasty Aki all right second one is pigments now pigments there's two types that I want you guys to remember about one is myoglobin and so with myoglobin we see this coming from often times skeletal muscles and the other one is hemoglobin which is going to come

from our red blood cells and so as you see here we have a perfect setup here there's one disease that causes a lot of myoglobin to get released from a tissue and this is usually skeletal muscle cells that are rupturing or breaking open and we call this rabdo myo Lis this happens in patients who have seizures or Crush injuries or they've been taking a certain drug like a Statin of sorts and this caus these skeletal muscles to kind of bust open a little bit and they release out things like creatinine KY or creatinase which is

kind of a marker of rabdo but it also releases out that myoglobin and the myoglobin is what's really kind of like dangerous CK is often times a parameter that we use as an aid to diagn diagnosis but the myoglobin is the thing that actually causes the disease here because what happens is this thing is going to run down through the Glarus get filtered out and when that myoglobin gets filtered out it can actually kind of directly cause damage it gets taken up by these tubular cells and when it gets taken up by these tubular cells

guess what well Daddy's home and he's going to cause some some jacking up of this problem here so that's the concept here with the myoglobin so you really want to look for seizures Crush injuries increased CK and an increased myoglobin or a urine myoglobin because we don't usually test the serum myoglobin we'll te test the urine if myoglobin right so if we test for actually like the myoglobin and the urine that would come back positive the next one is homolysis if we're talking about hemoglobin so hemolysis I would really more like see this with a

transfusion especially if it's acute because this is acute problems I would see this in like a transfusion reaction so they just got a transfusion how to pour you know reaction to it and then developed a homolysis of red blood cells and so what happen is that would cause your red blood cells to get popped right open right it would release hemoglobin and that hemoglobin would then do the same thing it would kind of go get filtered off get taken up by these actual uh tubular cells and that would cause direct injury to these actual tub

cells right the other concept here is that when we when we release this this hemoglobin into the bloodstream right you're also doing something else to the red blood cells you're also releasing something called LDH and LDH is kind of a marker that kind of tells us that we potentially are busting open a lot of these red blood cells another thing is that as hemoglobin is released into the circulation it gets bound to another protein and this protein is called haptoglobin and so haptoglobin is kind of a free circulating protein so imagine it here in pink

we kind of measure it based upon if it's free or not if it goes and binds on to hemoglobin then we lose some of that haptoglobin that's free and now some of it is bound to the hemoglobin and so what happens is is the haptoglobin levels will start to drop as it binds more and more of the hemoglobin and that's other ways that we can tell if a patient has underlying homolysis that's going on all right next one's crystals this is actually kind of like a very interesting one we can see this in a couple

like we can see this in a couple drugs a cyclo is one that we can give to patients who have underlying like you know viral infections of sort maybe herpes simplex but the real good one that we can kind of do for an exam is called tumor well let me I kind of gave the answer away dang it it's uric acid uric acid crystals and so these uric acid cryst crystals are something that we see as a result of a disease called tumor Lis syndrome because this would be a very very significant acute event what

happens is a patient has like lymphoma maybe non hodan more likely um or they have acute my myogenous leukemia and then they just get a bunch of chemotherapy when they get a bunch of chemotherapy they bust open these cells they release things like phosphate they release things like potassium they release things like LDH um and they even released a couple other substances but the big one tends to be uric acid often times there's aonic called puke which is phosphates uric acid potassium um and that's kind of the ways that you and then e is elevated

U you know these are all elevated elevated phosphate potassium and uric acid but these are going to be released a lot so you lots of uric acid lots of LDH lots of potassium lots of phosphate so these are going to be some things that get released as a result of these tumor cells busting open but the one that actually causes disease is the uric acid because what happens is this uric acid you get a bunch of it it starts to kind of bind with other molecules so other uric acid molecules and they start to precipitate

and when they precipitate and crystallize they can obstruct alumin but they also have the capabilities to cause direct injury and so they also can destroy these tubular cells and so that's the concept here all right so when we're thinking about these you're kind of looking through their medication list looking to see if there's any history of seizures Crush injuries drugs that can cause rabdo looking for homolysis and look at these parameters look at some of these Labs looking for a history of cancer with recent chemotherapy with some of these Labs all right the last one's

really tough this one's usually due to what's called bench Jones proteins so we have a lot of what's called imunoglobulin light chains we just call this bench Jones proteins we see these primarily um and a disease called multiple Myoma so multiple Myoma this is a plasma cell dis Gracia that basically these plasma cells are pumping out a bunch of proteins but these proteins that they're pumping out um unfortunately they're producing a lot of these like light chains and what happens is some of these proteins that they're producing will get circulated through out the bloodstream and

what they'll do is some of them may kind of like combine and precipitate and what they do is they love to kind of get stuck in the proximal tubule and when they get stuck in the proximal tubule they obstruct that flow and on top of that they cause direct nephrotoxicity and so that's another way that we can think about these These are these proteins that the plasma cells are releasing lots of these light chains these bench Jones proteins and they can also cause this big thing to remember though with this is that with multiple Myoma

it's also associated with a very common thing called The Crab criteria I'm not going to go through the whole thing I'm not going to write it all out but I want you to remember the crab criteria what I mean here is that these patients often times will present with hypercalcemia because hypercalcemia malignancy renal failure such as an acute kidney injury sometimes even CKD anemia and then lastly they can also present with bone pain because of the liic lesions caused by the actual plasma cells all right so this is the big thing that I need you

guys to remember for ATM is thinking about these as potential causes that we have to analyze in a patient who has an acute kidney injury and we suspect oh it's ATM because I've gone through and I figured out they have muddy Brown cast they have features on their Ur analysis which suggests that they have ATN we'll talk about those things and their phenon uros molality all suggest this what's the reason is it es schic is it never toxic and then go through these things in the systematic way we talked about if you've gone to a

patient they come in they have an acq kidney injury right CRS up your outputs down have a drop off in the GFR you're like H I don't really have anything that's really pegging me off to think about ATN then you can start thinking about a especially if they just recently started a drug often times acute intercensal fritis most commonly I mean I'm not kidding like most of the time and you'll most likely get a question on these more than you would get for infections it's very rare but you can see this with streptococus pneumonia and

you can see this with SLE and maybe even shogran syndrome but I'd say it's way less likely that you'll get see this and then also get tested on this it's more likely that you'll get tested on the drugs and so there's a lot of them and it's hard to remember everything and so one of the things that I think is best for us to do is using aonic and so I like to remember darn sap and so I remember this based upon D is for what all right there's a bunch of different drugs but diuretics

tends to be a kind of a potential offender here and so I think about Loop Diuretics I think about thide diuretics as a potential possibility here a I like to think about antibiotics and I would say more likely than not if you see a question where a patient just got a betal lactum penicillin amoxicilin sephos sporin any of them that have a betal lactum ring that is likely going to be the most common trigger all right especially for your Vettes other ones that you potentially could think about is refampin we can use this in tuberculosis

so that's something also to potentially think about another really big one is incets incets can also do this all right so non-steroidal anti-inflammatory drugs now other ones could be sulfa drugs any kind of sulfa drug could do this Baum any kind of drug that has a sulfa group group on it another one is alopurinol alopurinol we actually use this in patients who have underlying gout and sometimes in tumor liis syndrome and here's another really big one proton pump inhibitors like a meol so I'd say out of these which ones are the most likely that will'll

present in a VG yet as a patient who comes in they just taken a medication such as a betal lacum an insid or a PPI then after that that patient developed an acute kidney injury as well as other features a Triad of a we'll talk about it for right now I want you to trust me that it's usually a fever a rash and eosinophilia all right then you would start thinking about Ai and you would start looking through these potential drugs and just get rid of them all right often times more than not what is

this this drug is the antigen so this is the drug that like when we talked about before this is the drug that we become exposed to and once we become exposed to this drug it binds on to A protein that we are Expo like we have in our body and once we bind these two together this produces that combination of the drug and the protein which we now call what we call this a hapton and that hapton if you remember is what's immunogenic and triggers that whole process so here is the drug and then over

here we will have a some type of circulating protein molecule if you will these two when combined together make a hap and that's what triggers this immunologic kind of reaction that triggers lots of inflammation and edema in the interstitium of the renal tubules all right cool we hit this one we come to our last one over here the last scenario here is going to be renal papillary necrosis my friends this what's a tough one I wouldn't say that this is an easy diagnosis to make all right often times a patient who has renal papillary necrosis

they'll come to you and they'll come in with maybe flank pain maybe some hematuria but they won't have a lot of other symptoms often times they can be completely asymptomatic what you really want to think about with renal papillary necrosis that really helps you to think about this one is the causes so we know that it's the pill right right the the the deepest part of the pyramid that's undergoing necrosis because of the vessels you have small little vessels there and if for some reason you get kind of like an obstruction or compression of that

vessel you're not going to get enough blood flow it'll become necrotic it'll sloth off and you can obstruct kind of your kaix or your Ural system so we get that but what's causing that is the question there's many things and I'll talk about the biggest ones that I think are highest yield for your kind of exam but often times we use What's called the postcards demonic and we say that this could be due to pylo rtis now funny enough patients who have renal papillary necrosis can cause it could lead to pylon fritis because you can

obstruct their uror system and lead to bacterial stasis proximal to that obstruction but also pylon fritis causes an obstruction of the urer which can cause a back pressure and that back pressure can cause swelling inside of the kidney and that can compress those tiny little vessels at the pill and that can lead to esea another one is an obstru ruction of the urinary tract and so funny enough again same concept so pyloritis causes inflammation of the kidneys the inflammation of the Pilla squeezes the vessels and obstruction of the urinary tract like a stone that gets

stuck somewhere present within the urer or the Kix obstructs that flow and causes the pressure to build up and compresses those small vessels another one is sickle cell this is a pretty big one so patients who have underlying sickle cell anemia they can have those red blood cells that they can sickle and get stuck so if I get like a nice little good sickled cell red blood cell that sickled cell red blood cell can get stuck inside of our capillaries those small little vessels supplying the rain of pill boom you get aeia necrosis of that

tissue another one that's like super rare honestly I didn't want to put on the list is tuberculosis I'd say this is kind of a rare cause so the next one would be therosis now therosis is kind of interesting we can see this one as well it's usually due to portal hypertension that you cause you know the release of slank Vasa d ators and that kind of dilates your vessels and reduces the renal profusion because it kind of takes blood away all right and kind of diverts it to the git and instead pulls it away from

the kidney it also activates that renin Angiotensin ostrin system which vas or constricts your blood flow to the Glarus um another one this is a really big one is analgesia and we see this with inet so like okay Zach wait a second wait a second how do I know if it's the NES that are causing Ain versus the NES that are causing renal papillary necrosis they're completely different presentations and you should be able to pick that up off of the vignette we'll talk about that another one uh kind of less likely is renal vein thrombosis

especially if you have a patient that you think has an underlying nephrotic syndrome such as membranous nephropathy I would think about this one anales will talk about the mechanism renal vein thrombosis this works by blocking off the renal vein and that increases the compartmental pressure with inside of the kidney and that will cause compression of those small renal vessels another one is a really big one and this is diabetes metis very very common so diabetes mtis can actually cause Highland arterial sclerosis and it can really cause a lot of plaques to develop within those smaller

renal vessels and the last one that I would also think about is like systemic vasculitis so any kind of vasculitis has this capability to cause some type of process like this even like polyus and the DOA so the out of these which are the ones that I really want you to think about because and the reason why I want you to think about them is because they have mechanisms that you can be tested on but also if you think about patients who have underlying diseases you want to think about the ones that are kind of

like treatable right ineds the concept behind this is actually kind of cool incets work by kind of shutting down prostag gland and I2 and so what's happening is you're supposed to cause vasod dilation of these renal vessels right especially at the vasor recta if you have less pgi2 it's going to cause less Vaso dilation and instead cause Vaso constriction because that's the concept here is that if I have ineds what these are going to do is they're going to decrease pgi2 they're going to inhibit the cycle oxygenase enzyme and that's going to induce an increase

in the vas of constriction of these small renal papillary V vessels and then as a result if I Vaso constrict these puppies then what's going to happen I'm going to get less oxygen to this tissue it's going to become necrotic and as it does become necrotic it's going to sloth off some of that tissue into the Kix and into the Ural system CLE cells actually kind of interesting because again you get these like little CLE cells and these little CLE cells get go and they get stuck right so if I have these CLE cells and

they kind of turn to move and maneuver into this renal papillary vessel they're going to start plugging up this whole vessel and as you plug up this vessel you're not going to be able to get oxygen to this tissue if I can't get oxygen to this tissue what's going to happen it's going to start undergoing necrosis as it necroses it starts to die and shed and sloth off some of that renal papillary tissue and then lastly diabetes we know about this one it's going to cause a lot of artero sclerosis right because we know that

diabetes causes non-enzymatic glycation um and that kind of causes a lot of arterio sclerosis and if you cause arteriosclerosis of these vessels what are you doing you're kind of thickening up these vessels and you're narrowing that Lumen if I narrow that Lumen how hard is it going to be for me to get blood flow into this puppy it's going to be pretty difficult and as a result this tissue will start to become es schic and necrotic and it'll start to sloth off some of that tissue and so I think that's the big things to be

able to remember with these patients is that again you're looking at this in the sense of what is causing me to not give enough blood flow to the renal pill it's usually due to an obstruction in the Lumen of the vessel such as in diabetes Sickle Cell um it could even be in the scenarios uh such as um other diseases like maybe external compression so things like pylon nephritis can cause an external compression because of inflammation obstruction of the urinary tract is increasing the compressure inside of the kidney uh even renal vein thrombosis increase the

pressure inside of the kidney and you're squeezing on that vessels it could be vasor contriction with the vessels in the scenario of ineds right and so I think all of these are things that you have to think about is how are we causing papillary esea all right now that we've gone through each one of these guys pathophysiology their causes now what we have to do is say okay what are the likely presentation of these patients how would they come and see us as a practitioner and then how would I analyze those complications that they're presenting

with and say okay I need to get a diagnostic approach going on here afterwards let's do that all right so we have a patient who comes in right maybe they have a qtub necrosis you're trying to figure out what are the likely presentation or complications that they may come in with often times an acute kidney injury is the primary way that we would find acute tubular necrosis right so the concept behind this is also you know again repetitive to some degree in the sense that you have these tubular cells that have died due to es

schia or nephrotoxins or whatever it may be and whenever they die they kind of plug up they SLO off and they start plugging up this tubular Lumen when you plug up the tubular Lumen we know that this is going to impede the flow of filtrate right and what we know is is that this will increase the capsular hydrostatic pressure and as we increase the capsular hydrostatic pressure that then shuts off the natural flow of what we would say is the GFR right so we're going to shut down the GFR so there's again an increase in

the capsular hydrostatic pressure and this increase in capsular hydrostatic pressure will shut down the net filtration right and as a result the patient will start to have less urine output right so if you're not filtering things down through the tubular system you will start to expect a decrease in the urine output what do we what do we call this so we call this aligera right so they can have aligera the other thing is that if you are having again blood contains all kinds of different things right especially waste products if I'm not filtering these things

across the Glarus what's going to happen they're going to stay in the bloodstream and so often the primary marker that we look at for an acute kidney injury is that these patients will have a increase in their serum creatinine and an increase in their bu and so that's what I want to watch out for is an increase in the creatinine and again if you remember what the the numbers we we describ them as in the Aki lecture and an increase in the bun right the other thing is that this can also cause a lot of

other problems right so these patients can start to experience a lot of complications of Aki what are some of these Aki complications it can cause an increase in potassium increase in water and an increase in protons and so these patients are high risk for hyperkalemia they're increased risk for hyperemia and increased risk of acidosis so if a patient retains potassium retains sodium and water and retains protons these are high risk for things like hyperkalemia hyperemia acidosis and these two can lead to ureia and so that's the things that you have to watch out for here

is hyper calmia uh hyper vmia acidosis usually this is a Ani Gap metabolic acidosis and then last lastly is ureia so this is azotemia which is kind of an increase in the metabolic waste products but if this causes complications it can lead to uremia especially things like encylopedia but that's one of the biggest things that we have to be concerned with another thing that's really important here is when we test these patients urine they have very interesting phena findings so what we find is that they have a high fena so we what I mean by

this is that they have a fena that's usually greater than 2% and they have a uranos molality that suggests that the patient is not able to retain water so it's less than 350 and let me explain that for a quick second so when we talk about these patients who have acute tubular necrosis what we know is that they have a kind of a high fena and this basically tells me are they able to reabsorb sodium or not so what I want you to remember is that again the these tubular cells are dead it's most likely

proximal but you can affect other tubular cells what happens is is normally you're supposed to be able to reabsorb sodium in the proximal tubules and the distal tubules and usually this is regulated by hormones right so this one in the distal tubules usually aldosterone regulated and then the one here in the proximal tubules like Angiotensin 2 or just even like you know regulated based upon passive and active movements but even if Angiotensin 2 is present and aldosterone is present it wouldn't really matter because these tissue cells are damaged and their ability to respond to these

hormones doesn't really matter and so their ability to reabsorb sodium across the proximal IND distal tubules is impaired because it doesn't matter if these hormones are present or not as a result you don't reabsorb sodium across the tubules and so as a result the sodium retains in the tubular system and gets peed out and so these patients have a very very high urine sodium and when you look at their High urine sodium and you plug it into the equation a phena it's going to give you a high phena all right urine hos molality is also

a concept here where water is usually reabsorbed across the proximal tubal and the distal tubal now it's primarily you know modulated here based upon osmosis and here it's regulated by ADH right it wouldn't matter though even if ADH was in high levels or not because if these cells are damaged their ability to respond to these hormones or their ability to reabsorb things is impaired and so what happens is you don't reabsorb water so the ability to reabsorb water is lost and so as a result the water stays within the actual tubular system and gets lost

into the urine and as a result you get a ton of water and the urine and we call that a dilute urine and whenever you have a dilute urine the tenic or the osmolality of that solution is then going to be low and so that is what causes that low urine osmolality which are going to abbreviate uosm so that's the concept I want you guys to understand here with ATM we talked about this a little bit in Aki this is just a nice recap the last thing and again we kind of talked about this multiple

times already but really important to acute tub necrosis is when you assess these patients your analysis with microscopy so you take a look at their UA with microscopy what we will notice is is that these dead tubular cells whenever they kind of like SLO off into this tissue I mean into the Lumen they take on the shape of the lumen and so what it does is it kind of forms like this like weird kind of shape here which we call a cast and so this is what we're going to say is a cast which is

basically a clump of epithelial tissues right that is formed by the proximal convoluted tubular cell Lumen and we call this muddy Brown cast this is super characteristic of a patient with ATN all right so atn's will present with an acute kidney injury potentially complications associated with it but look for these urinary findings to really help you reel in the concept of ATN as compared to these others all right so now we talk about acute inition nefritis again this is not a very common cause of Aki in other words when we talk about akis pre-renal akis

70% of 67% them are pre-renal uh and when we talk about intrarenal Aki like 80 to 85% of them are ATN so it leads like maybe 10 to 50% of the patients who have Aki to have you know acute interal frus if it's intrarenal but either way it's something that we have to be considering so if the patient has recently taken a medication one of those darn sap medications right then you should be thinking about this especially if a patient comes in they have an acute kidney injury again concept behind this one if you guys

remember um we had some type of inflammatory cell infiltrate so you were exposed to the drug the drug then did what bound with a circulating protein that circulating protein became a hapon the hatin has immunogenic potential the immunogenic potential led to antigen presenting cells doing what presenting that Happ to a te- cell te- cells then say okay let me go ahead and release a bunch of P cyto homie releases a bunch of cycin like Incan 5 and then what they do is is they recruit lots of you know immun sit themselves but I'd say the

big one is eosinophils into this interstitial Lumin uh interstitial tissue area what that does is increases the edema and when you increase this edema here what is it going to do it's going going to start compressing it's going to start squeezing on the tubular system as you compress the tubular system you narrow the Lumen as you narrow the Lumen you make it sure as heck harder for things to filter across here as you can't filter things across the Glarus things begin to build up in the bloodstream right and then also you lose the ability to

make urine so it's the same concept as ATN right as blood kind of comes through here I lose the ability to make that urine so goes down and I lose the ability to get rid of waste products and so these waste products begin to build up in the bloodstream and so again same concept I'll experience a decrease in urine output increase in crat increase in bu in potentially complications such as an increase in potassium increase in sodium and water and an increase in the acidosis so again what is it called when we have a reduce

urine output my friends this is aligera right and if it makes no urine it's anua increased creatinine is a really big one right increase in the bu this is called azotemia but if it builds up enough and enough and enough that it causes complications we can call that ureia build up in potassium a build up in sodium and water retention and a build up in protons what does these things again cause this can lead to ureia if it causes inphy opathy paric carditis and bleeding can lead to acidosis hyperemia and hyperemia and again this acidosis

is a anti Gap metabolic acidosis this hypervolemia can lead to a lot of Edema features and the hyper calmia can lead to EKG changes in arrhythmias so we know that this is a potential presentation right of a patient developing an Aki what I think is important to remember is that these patients who have akis they often times not only present with these things but other features that separates them from ATN so so Ain they can have variable urine osmolalities variable phenos and what's really interesting is that they often times will present with a Triad and

when I say oftentimes on your boards all the time in true clinical reality 10% of the time and this Triad is often consisting of things like a fever so watch out for a fever watch out for a morbilliform rash and then lastly because of that interlan 5 that's heavily secreted watch out for increased eosinophils or eosinophilia now the other thing that in real life has very very very low sensitivity and specificity and utility is a UR analysis for these patients so if you test the urine for these patients what will happen is when you do

a urine analysis with microscopy is you may see something that suggests that there's a lot of white blood BL cells into the urine so you may see a lot of white blood cells that are getting kind of stuck into the shape of this actual tubular Lumin and when you go ahead and you actually look at these under the microscope again what you'll see is that you'll have white blood cell casts but when you look at a lot of these white blood cells what you're going to notice is that they contain lots of eosinophils again the

likelihood of this on the actual clinical reaction ity is very very low you know urania cils doesn't actually kind of tell me that a patient has Ain and true clinical reality can be any kind of disease but for your exam if you see high urania cils and Aki fever rash definitely be thinking about Ain especially if they had a recent drug exposure the last one is renal papillary necrosis now this one's interesting the chances of causing an Aki is kind of rare what would have to happen here is you would have to have like extens

papillary necrosis right or you would have to have bilateral papillary necrosis so really in order to have an Aki which it is possible I would say it needs to be bilateral and it needs to be extensive and the the likelihood of this being something that is likely going to cause an Aki I don't want you to waste all your time thinking about it as a common cause of AI it's not it can but it's not a common cause it would have to be super extensive because because the concept here is is that this tissue this

sloft off tissue would have to kind of get stuck here it would have to get stuck in kind of like your urer system and if it gets stuck here it causes a backup right so it backs the pressure up into the kidneys and impairs your filtration process so you can see an Aki but I'd say it's less likely it usually needs to be bilateral renal papillary necrosis or extensive papillary necrosis p nephritis on the other hand this one I would say is very common the concept here is again you have necrosis of this tissue it

sloths off when it sloths off it gets stuck here and again if it gets stuck here what's the problem with this well then again you're going to cause a back flow but you know what's supposed to be constantly flowing out of our genital urinary tract bacteria and if bacteria is not being cleared guess what's going to happen the bacteria which we'll represent here in kind of this uh we'll do this pinkish color here it's going to start building up in the kidney and if this starts building up in the kidney it's going to cause an

infection of the kidney and that's called Pyon nephritis so with an acute kidney injury yes it usually needs to be bilateral or extensive necrosis to truly cause an Aki with pylon fritis it can be a cause and it can also be a result of renal papillary necrosis so that's actually really important to remember usually for this one you want to watch out for fever you want to watch out for flank pain but I I think here's the big thing usually when a patient has a UTI which we haven't talked about in this system we'll talk

about an infectious disease when you get a urine analysis with microscopy on these patients one of the big things that helps out here is you see a couple different things one is that you'll see that they'll have slothed off papillary tissue they'll have a lot of white blood cells they have lucite esterases and nitrites and they'll have bacteria so when you look for a patient with pylon arrius look off look for a papillary necrotic tissue look for increased white blood cells right and then usually they're in a cast formation another thing is look for lucite

esterase to be positive and nitrites to be positive and then lastly look for the presence of bacteria to be present right and so these are the things that I would really want you guys to be considering in a patient who has pyloritis they're going to have pain they're going to have fevers and on top of that they're going to have these urinary findings with an acute kidney injury you would more likely just see an elevation in their creatinine all right but it's not as common I again I want you to remember less common common it

just shouldn't be on the the high differential of but Aki all right next thing flank pain with this necrotic tissue again we're kind of repeating it here but if this tissue sloths off and it's big enough that it obstructs the uror system if it obstructs the uror system what's going to happen again we know it can cause a back flow and cause an Aki but another thing here is it's going to cause the back flow to lead to maybe distension or kind of enlargement of the kidneys and what's that called hydron nephrosis and so if

a patient gets hydrosis you can cause this patient to develop some flank pain and this is because of kind of just a a fluid logged or overloaded kidney where you can't get urine to flow out because you have a slof off piece of dead tissue that's obstructing the urer flow all right the last thing is hemera this is actually pretty straightforward I wouldn't imagine to be super complicated but if you have you know this dead epithelial tissue when you're kind of causing necrosis of the papillary tissue remember there's small little vessels in that area and

if you rupture them blood is going to kind of be released into the cxes and then they'll get dumped into the urer system and so it isn't very very common in these patients super common that if you see sloft epithelial tissue guess what else you're going to see you're going to see not just epithelial tissue there you're going to likely see blood and this can be macroscopic or microscopic so hemu is super common in combination with the papillary necrotic tissue so when I have a patient with renal papillary necrosis what I look for is not

necessarily Aki as I would say with these I would say look for a patient who comes in with flank pain hematuria potentially pylon nefritis features are features that are hard to distinguish from pylon fritis and then say what are their likely history do they have the postcards pneumonic diabetes nads use Etc that we talked about and then from there we can do another test that we'll talk about in the diagnostic section to really help to reel Us in and say oh this is definitely renal papillary necrosis without that you know further going any more into

this let's now say okay how do we truly get a good diagnostic understanding of these tubular interstitial disorders all right so we've taken all of these patients I'd say ATN a they more likely present with an Aki renal papillary necrosis more of that flank pain the hematuria Maybe maybe some pylon nephritis so if I have a suspicion of any of these I'm really going to want to have enough wide testing that I'm going to pick this up so I'd start off with the urinalysis with microscopy I get a phena and I get a urine osmolality

the reason why is this going to give me a lot of information the urinal with microscopy will tell me if there's certain types of casts or sloth tissue the phena and the urinal mality will tell me if this is likely ATN or not so let's say that I do this I got white blood cell cast oo okay especially if it's a lot ails that was a oh okay there's uril that's probably a all right well then what's next history okay why am I going to get a history oh yeah it look to see if they

were having any of those darn sap medications that they were exposed to right so were they on diuretics of any sorts right but again what was the big ones that I want you to remember the antibiotics the betal lactum maybe refampin is another potential one there as well ineds and again we talked about sulfa drugs uh we talked about alopurinol we talked about ppis but again I want you remember the PPI the nids but big one is the betal laom antibiotics what else was another feature in the history fever rash all right so if I

have fever rash eosinophilia um and then I got urine eosinophils white cell cast and darn sap medications boom I got my diagnosis this is a the next thing is if I see muddy Brown cast oh that was aen all right cool the phenon the uros mality though that tells me that the tubules aren't working so the feno's got to be high because they're not reabsorbing it and the urinal is low because they're not reabsorbing water all right cool so that's likely ATN what do I need though well if I get the history I got to

look for ES schea right and scenarios of shock so look for very poor blood pressure so hypotension are they hypmic shock septic shock cardiogenic shock or is this nephrotoxin mediated so any kind of drugs that I talked about that are in their medical record that could be a trigger have they had any evidence of rabdo any evidence of hemolysis all right cool none all right well have they had any potential crystals is there any evidence of cancer that can cause toris syndrome oh no is there any features that suggest like a crab criteria like multiple

Myoma oh no okay so I got to go through those things and think about the potential history that would suggest that but if I have the history of esea or I have the history of nephrotoxins that's probably the likely trigger and I would say with good certainty that this is probably ATN now if I get this and I see slothed off renal tissue uh with hematuria then that's really making me think about a patient having more of a renal perinal disease and the scenario of renal papillar necrosis but in order to truly make that diagnosis

I really want to have a patient who has something like sickle cell anemia or chronic diabetes or very chronic inid use because this is a niche diagnosis I'm looking for flank pain I'm looking for the hematuria with again a non glomerular hemia what does that mean again no red blood cells no red blood cell cast no dysmorph I mean no red blood cell cast no dysmorphic red blood cells no heavy protein Ura they'll have that sloft renal papillary tissue if I really think that this could be a especially in Sickle Cell chronic inid use or

diabetes I got to get a CT urogram and the reason why is that's going to show me that signate ring sign that usually is indicative of the necrosis here in the pillo and that would kind of nail down my diagnosis of rpn all right so we've made our diagnosis of these how do we treat each one surprisingly it's very straightforward you just treat the underlying cause right so if the patient is taking if they have ATN either way you should avoid nephrotoxins to avoid recurrent injury all right so avoid that consistent injury that could worsen

their ATN worsen their Ai and progress them to dialysis potentially um if their blood pressure is low you got to fix it if it's due to hypovolemia give them fluids if it's due to septic shock and their blood pressure is low despite fluids then you got to give them Vaso pressors keep that blood pressure up keep profusing the kidney so that we don't have them have consistent damage because if not the Aki can worse and then I got to start reaching out to my nephology colleagues to dialyze them especially if the patient's having refractory acidosis

refractory hyperemia they're having Hy hyperemia that I can't diares off or they're having ureic complications all right now Ain this one's actually often times self-limiting again you just kind of just remove the offending trigger if you can remove the diuretics the antibiotics the betal lactum or at least switch it if they have an infection switch it to one that's not going to cause Ain uh try to switch it to an alternative type of antituberculosis medication try to avoid inets try to avoid the sulfur drugs if possible try to maybe consider an alternative drug at to

Al alopurinol maybe switch from a PPI to an h2ra if able this is going to help us to reduce that recurrence of Ain the other thing here is that with these patients if it's in the early stages the first seven days of the disease you could consider corticosteroids but again it's usually if the patient has severe Ain in other words they have a very bad Aki that's when you would consider potentially adding on steroids if you discontinued or switched to an alternative drug and they continue to have an Aki and it's in the first seven

days you can give corticosteroids it's unlikely but a patient can progress to needing dialysis if they have the same indications that we talked about in ATN now for renal papillary necrosis this one's actually pretty straightforward again we talked about that postcards nemonic with the big ones being Sickle Cell the biggest one being the inid the diabetes and potentially obstruction if you treat those underlying diseases you should prevent the recurrence of renal papillary necrosis but often times again trying to think about those scenarios like discontinuing the medications is very important especially if it's in this scenario

if it's CLE cell you may have to consider giving things like hydroxy ARA to reduce the incidence of these vasoocclusive crises um if it's due to diabetes unfortunately there 's not much that you can do except for try to improve their glycemic control so Etc trying to treat the underlying cause is the key if they develop other complications related to that such as pylon nephritis you can give them antibiotics if they develop an obstruction that's they can't actually get through because the necrotic tissue is truly obstructing them they may be able to go in and

place a stin to allow for improvement of urine flow all right and that's kind of just showing us that we would take our guide wire up try to remove that SLO tissue or at least put in a stent to improve the movement of that sloth tissue and urine flow my friends that's tubu interstitial diseases I hope it made sense I hope that you guys enjoyed it love you thank you and as always until next time [Music]