The "Brilliant" Kidney

Stanford University well good evening everyone great to see you again tonight last week when we were about to hear our presentation on the GI tract I asked how many of you had had dinner before the event tonight I'll be more courteous to not ask you how many have gone to the bathroom but you will either have just beforehand or sometime after would and just think about this you know when you think about voiding it seems like such a simple process and what I think you're going to appreciate after this evening is how intricate and important dark kidneys are to our overall function regulating not just fluid balance but all the electrolytes in our body system which actually regulates the integrity and configuration of our cells allows the balanced pH balance in our system to be carefully calibrated so that all of our enzymes and proteins work effectively helps to organize our blood pressure among other things and carries with them because there are two kidneys as you know enormous capacity and redundancy so that you could actually get down to what about 1/2 of a kidney and still function now or even a fraction of 1/2 maybe one nephron is we'll hear later this evening if you're really successful and so tonight I'm very pleased to have Glen turtle who is the chief of the division of Nephrology kidney specialist at Stanford in the department of medicine as our speaker dr. church out join Stanford in 2007 he's yet another person that we recruited from another institution in this case UCSF we try to borrow the best from them but he also had his time on the East Coast he did his undergraduate work at Penn and then went to Harvard Medical School and in addition to studying nephrology and becoming an expert in kidney disease at the Brigham and Women's Hospital and functioning on the important renal function he focused on population science and epidemiology as well so he has a broader playing field of areas of expertise that he is particularly knowledgeable in we asked him this evening since he's joined us and been such an exemplary leader to help elucidate the important balance that the kidneys play in organizing our body systems and I'm sure you're going to enjoy that now I have a minor confession to tell you if you can hear my voice if you're paying attention carefully and you remember the lecture just a couple of weeks ago on the auditory system you'll know that I'm not speaking very clearly and that's because say if this were an infectious disease session I would be diagnosed with a significant disease so I just called in a prescription for myself you can't do this but I did and I know the pharmacy closes at about 8:00 so at about 7:30 I'm heading off so that I could restore my own body I'm sure you'll appreciate that as well so don't mistake my Exodus it's really self-preservation and isn't just because I need to go to the bathroom and so without further ado Glenn thank you thank you dr. piso it's really a privilege with the exception of the light staring me in the eyes it's really a privilege to be here this reminds me since as dr. piso mentioned I'm a transplant of sorts from UCSF and I still live in San Francisco so I'm fearful as I Drive down to 80 it's such a beautiful road and it's so easy to begin to exceed that speed limit of 65 that light is something I worry about on a regular basis in any case I hope that by the end of our session today you may well be able to if not call the pharmacy to prescribe yourself some medication perhaps call the supermarket or the fridge and prescribe yourself some appropriate fluids in any case I think at the risk of potentially jeopardizing my career I might say that in lieu of the hematologic system which is of course brilliant I would I would say that that among the things that that I'll try to convince you is that the kidneys are the most brilliant organs in the body with the exception of the brain but again I probably shouldn't say that within earshot of a hematologist oncologist so I'd like to thank one of my colleagues dr. Timothy Maier who's a magnificent educator for sharing a couple of the older-looking slides which really had some marvelous pictures and beautiful diagrams so thank you to Tim so I wanted to give you a context just a small historical context about the kidneys because we really don't get we now I'll talk about we as the kidneys we don't really get as much attention as the brain or the heart of the blood but but we're not only pretty smart but we're actually really cool um so you've heard about Vesalius pasture and others but verse shall the pathologist who studied cells of course made a beautiful statement in I don't remember the year in the mid 19th century describing Lamia interior the stability of the internal milieu is a primary condition for the freedom and independence of certain living bodies in relation to the environment surrounding them so what I'll try to do today is talk a little bit about the internal milieu and how the kidneys modulate that and how they can miraculously help us survive in a desert or in the setting of water excess and we'll talk a little bit about some of the very basic issues of distribution of body water and electrolytes in the body and for fun at the end we'll talk about a couple of interesting cases and these are the types of cases that we might discuss with medical students and I think you'll see based on their complexity and their interest why they would either very powerfully or potentially attract students to our field every everyone wants to do hematology and oncology nowadays there are such exciting discoveries and nephrology is rather unpopular but I'll try to convince you that that's a big mistake so I'd like to suggest that modern physicians are surgeons that is exquisite surgeons of the extracellular fluid I'm just going to give you some schematic diagrams for you to think about because when we think about the body tissues and body water we don't often think about body compartments but it's extremely important when we think about how the kidney regulates these electrolytes in fluid and some of the disorders of fluid and electrolytes that we'll touch on a little bit later I also would mention that I'd be delighted if anyone asked questions particularly people on the side of the room so that I don't have to stare into the bright light I have about 40 or 45 slides as I recall and that gives us plenty of time to be interrupted and plenty of time for discussions at the end so please feel free to interrupt and ask questions while we're while we're speaking I'd like this to be very interactive it's much more fun that's one of the this is the room where we do our medical Grand Rounds and dr. piso often attends in our department chair makes it really makes it a theater it's entertaining and fun and so I'm not nearly as entertaining as he he has great glasses with little purple polka dots on them but but please feel free to interrupt so basically we have this cellular environment and the extracellular environment we're going to talk about this a little bit and in the cell there's stuff and that stuff has properties that hold water and so do the properties of the extracellular fluid and so these are generally called awesomes or osmolytes or depending on who you talk to toner moles or tonicity but these are our elements that are dissolved within the fluids either in the intracellular space or the extracellular space that are responsible for the composition of the fluids and the body works very hard to maintain neutrality and homeo you've probably heard the term homeostasis or balance this is a property of our bodies this is how we're programmed kidneys contribute greatly to homeostasis but the other organs contribute to that as well and in general we work very hard we can being the kidneys we work very hard to maintain electroneutrality that is the balance of electrical charges osmotic neutrality that is the balance of these stuff that's dissolved in the fluid within the cells and outside of the cells and in fact this principle of permeability of fluids across membranes and the permeability of some substances and the non permeability of other substances is really the the foundation on which our cells are built the energy that our cells use to maintain differences in balance are what really occupies most of the energy and it's these differences in the electrolytes within and outside the cell that make cells work so we'll discuss what makes the makeup of the inner part of the cells in the outer part of the cells a little bit later and we'll talk a little bit about that in the context of some of the fluids and foods you're going to choose when you go home tonight or maybe when you came in so we'll think about intracellular and you'll hear me use these terms and forgive me if I if I use terms that are not well understood just interrupt and let me know I'll try not to but intracellular fluid refers to the fluid that's within the cells extracellular fluid is the fluid outside the cells and that fluid outside the cells is complex it's also compartmentalized so that fluid can be either the plasma which is the fluid that occupies the blood vessels or what's called interstitial fluid and the interstitial is if you will the matrix the infrastructure of the outer cells and so you have the intracellular environment in the extracellular environment and in the extracellular environment you have the blood or the blood vessels and the plasma in the blood the plasma being a mixture of blood and a mixture of electrolytes and other proteins that fill up the blood and then you have the interstitial fluid which is also outside of the cells so they're all in our bodies you can see those fluids but they're compartmentalized and I think often people don't realize actually how little fluid there is circulating around in our blood vessels and we'll do some of those calculations but you might be surprised does anyone have a guess say how many liters are circulating in an average-sized person at any one time 12 liters 8 liters 5 liters 2 liters well that's pretty good we have a good range 12 to 2 so yeah it's somewhere in between 12 and 2 it's definitely more than 2 except not in a neonate it would be less than 2 but for most adults it would be more than 2 it's it's certainly going to be less than 12 probably 3 to 5 5 and a half would be about right but we'll go through some of those calculations tim-tim Meyer my colleague who's really our divisions premier educator he's he loves the equations and I I like the equations I think there are just a couple of equations to you know that really help illustrate some of the some of the principles of balance which is what I'm going to try to touch on today I'm not going to get into very complicated equations though I think for fun and to prove to me that you're ready to call in that prescription for either pretzels or cardboard that that will do a couple of exercises later so this is a diagram do I have a pointer I'm technologically and directionally impaired so if anybody wants to you know turn me around once or twice I'll not know where I am yeah sure I'm sorry well in any case this um oh thank you thank you so much this slide depicts what I just described being the intracellular fluid and the extracellular fluid with the extracellular fluid being split among the two compartments or between the two compartments the plasma compartment and the interstitial compartment and we'll talk about the relative size of the intracellular compartment and the extracellular compartment in a moment just by way of guessing who thinks show of hands that the intracellular compartment that is the fluid that's inside the cells is larger or smaller than the extracellular compartment the fluid outside the cells in general so who thinks the fluid inside the cells is larger are you sure we could do who wants to be a millionaire who thinks that the extracellular fluid compartment is larger there's more in the extracellular fluid more interstitial and plasma fluid in fact the intracellular fluid compartment is larger in virtually all cases of health occasionally in a very unfortunate patient say in a burn unit in the intensive care unit the opposite may be true but almost always the intracellular compartment is larger so the fluid as I mentioned the fluid that's in the cells has a different composition than the fluid outside of the cells and this is depicted here with a little bit of color coding so we can see that there's a lot of potassium in the cells there's very little potassium outside of the cells there's a lot of sodium outside of the cells there's not a lot of sodium inside of the cells so it turns out that the cells create these gradients to allow for their complex functions and creating and maintaining those gradients utilize energy and if you look these are the positively charged ions called cations that are in the extracellular fluid space and these are the negatively charged ions or anions that are in the extracellular space and you might recall I said that that physicians are the surgeons of the extracellular space we don't do a lot generally speaking since we have access to the blood the plasma we're really modifying the extracellular space the intracellular space then becomes involved because these are our fluid no pun intended compartments but this is where we're really doing our business so you see that the majority of the extracellular anions our chloride so that's interesting in view of a very important paper published by Stanford physicians today in the annals of internal medicine on the cost-effectiveness of interventions that might reduce salt intake which I think yeah which I think complemented complimented a study we published just last week on the anticipated health improvements that might be gained by a reduction in salt intake so you see that sodium and chloride the components of salt are the main cation and anion of the extracellular space so if if you before you came in had a bag of Fritos or Lay's potato chips you have probably replenished at least temporarily until your kidneys protected you you probably replenished your extracellular space of its predominant cation and anion but thankfully you have kidneys so let's do a quiz a pop quiz the sodium concentration outside of the cell outside of the cell would also be called extracellular excellent is approximately 150 150 or 10 milli equivalents per liter okay raise raise your hands 150 milli equivalents per liter 100 milli equivalents per liter round numbers are always good okay how about 50 milli equivalents per liter how about 10 milli equivalents per liter milli a quat simili equivalent okay we can talk about that well this was kind of cheap it was just to see how carefully how carefully you were paying attention these are milliequivalents so the sodium concentration is about 150 milli equivalents per liter it's a little bit less it's more like a hundred and forty you can see there are some other cations the overall osmolality of the plasma and the osmoles are the stuff the stuff that holds the water if you're electrically balanced you have about 150 of the cations about 150 of the anions it's about 300 that's the osmolality it's generally a little bit lower about 290 but 300 is a good round number sodium is about 150 chloride plus bicarbonate all of you have a box of baking soda in your refrigerator probably that's sodium bicarbonate see all these things are in your fridge and your in your in your pantry so we'll talk I have a slide should I should have put it here just to talk about the milli equivalents and milli Azam's now if just to see where you are with your body compartment sense right now if you were to infuse a saline solution and saline is a term that we use for salt and water so a salt water solution into a person's vein where does the sodium go immediately and remember they're fluid compartments but do they go into the vascular space into the vascular and interstitial spaces or throughout the body water so who says throughout the body water number three that sounds like one of those all-of-the-above answers that make you feel good in a standardized test yeah that's not I mean that's not true so does it go into the vascular space or does it go into the vascular integer and interstitial space I see people are saying vascular and interstitial why the are you a couple or just friends exactly exactly so the answer the question so I asked the question does this go into the vascular space where does this go into the into the vascular and interstitial spaces and remember the salt rich fluid is the extracellular fluid the sodium chloride cation anion that extracellular fluid is part plasma part interstitial so when you infuse saline or a saltwater solution it doesn't go into the cells because the salt the sodium chloride does not exist in high quantities in the cells it's pushed out of the cells so nor does it go into the vascular space so let's imagine that someone were were bitten by a saber-toothed tiger and we're bleeding from his or her leg and we wanted to replete the vascular space would it be what would be the most efficient way of replenishing the fluid in those 3 to 5 liters that exist in the vascular space excellent answer so the answer would be stopped the bleeding but if if you could stop the bleeding but you still needed to replenish the fluid would you give and I'll give you three choices and you know this will qualify you as a junior emergency department doctor would you give dextrose in water a very commonly infused solution would you give saline or would you give blood saline yeah if there were blood available you would probably give blood because blood goes right into the vascular space it stays there blood is red blood cells predominantly so that stays in the vascular space that would be the most efficient in contrast if you gave saline we've just learned saline would go into the vascular and interstitial spaces so it's actually not bad it's reasonably efficient for every milliliter of or every ten milliliters of fluid that you gave of saline that you gave maybe three of them would go into the vascular space and seven of them would go into the interstitial space that's pretty efficient as opposed to total as opposed to the dextrose and water solution yes right so dextrose in water there's water everywhere and the wheat ah I use the term semipermeable membrane earlier and I use that term that's a very special term to a nephrologist who cares for patients on dialysis because we're creating semi permeable membranes for artificial kidneys because in dialysis and we'll talk a little bit about dialysis at the end I noticed in your in your really lovely text there was some discussion about dialysis nothing about transplant at least in that section but in any case the membrane the cellular membrane is permeable to some things and impermeable to others which is why we call it a semi permeable membrane it is perfectly permeable to water so if water is infused into the vascular space it can permeate in everywhere so in fact it would be very very inefficient way to restore the volume plays mavala myth one had been bleeding giving dextrous and water would give a little bit of extra fluid into the vascular space but the majority of that fluid would go out outside of that vascular space and this is why when someone is in shock we often use blood and there's so much interest in using other plasma expanders to help people in shock say after after traumatic injury thank you for clarifying that so let's take part me another no no yes you are Percy you are the light you are precisely the light so that's a very good question so the other question is what are some of the other plasma expanders so other things that don't that stay in the in the plasma space and don't permeate into the interstitial space of the extracellular compartment or the entire total body water including the intracellular compartment so probably the most common plasma expander is serum albumin which is aside from hemoglobin and red blood cells there I may have redeemed myself for a moment by mentioning red blood cells but aside from hemoglobin if I'm not mistaken albumin is the most abundant plasma protein or sometimes people are infused plasma actually the non-blood portion the non red blood cell portion of the blood which is plasma proteins albumin antibodies and other materials and they don't escape out of the vascular space into the interstitial space there are also some some manufactured volume expanders with the same qualities but the idea is that it fills up the vascular space and it doesn't permeate into the other spaces so let's talk a little bit about some of these terms that we've been using I'm sorry another question away from the light oh boy you know that's a great question and I haven't thought about that there's a lot we I could calculate that and get back to you not as many as in a big bag of Doritos no I'm just kidding I'm sure there's more I'm just trying to scare you so when we use the term millimole it refers to one one thousand one one thousandth of a mole of ions or molecules a mole is a unit of measurement when we talk about milli equivalents it's equivalent to a milli mole of charge so we talked about the stuff and sometimes the stuff is charged and sometimes the stuff is uncharged so let me ask you a question about that is sodium charged yes his chloride charge is bicarbonate charged yes is carbonate charged of bicarbonate is charged probably carbonate is charged yes is dextrose or glucose charged no exactly is urea charged no it's not actually in urea boy you'll really start seeing me smile if we start talking about urea haven't you heard that song you know how do you solve a problem like urea how do you cure a rising B UN it leads on but you know in the interest of time us I'll spare you except for the end which is if kidney disease isn't causing this thing so well we'll do that later for the encore anyway nilly ah Soames our one one thousandth of a mole of particles in solution so we talked about millimoles when we talk about something being one millimole per liter of glucose gives a 1 milli oz molar solution does that contribute any milli equivalents no I just know it's something RINO my nose tells me this if kidney disease isn't causing this thing then why do they smell like piss so so let's for a moment calculate the osmolality this is one of Tim's slides you can see it's gray how do we calculate the osmolality of a 5% dextrose solution and this the 5% dextrose solution dextrose and water is one of the commonly administered fluids in the hospital I mentioned to you a moment ago that it's not an efficient way of restoring blood loss or plasma loss but it's a very good way of giving maintenance fluid because generally speaking I'm drinking water and I'm hydrating and that's my maintenance do I drink water every day or do I drink brine I drink water now this is very common misconception in the hospital even among house officers in some physicians we've we talked about a bag of flu and I'm going to show you this is a bag of 5% dextrose in water I'll seal very commonly administered fluid one of the quote unquote maintenance fluids we when we talk about saline normal saline and we'll spend a moment talking about that in a moment that's also often used as a maintenance fluid and does anybody know what the concentration of sodium chloride is in saline point-9 did someone say point nine point nine percent that's exactly right point nine percent you get a degree and what is point nine percent mean in terms of the concentration in grams of sodium per liter so the percent is a convention to describe grams per deciliter or one tenth of a liter so if there's 0.9 grams per deciliter how many grams are there in a liter nine grams okay so those are the kind of formulas I like you know they're pretty easy so who knows what the average daily intake of salt is in the United States how many grams to grams those of us who care for patients with heart failure and kidney disease could only wish so well guess again 20s a wow that's a lot there are people who eat 20 grams of salt a day no question but it's about it's on average in the United States now ten and in conjunction we'll just take a step away because this is really important to the public health that along with this unfathomable rise in the average body weight of the United States over the past 20 to 30 years an unimaginable rise in the average body weight we've seen a in parallel rise in sodium intake does anyone know what fraction of the salt intake we derive as US citizens from processed foods processed foods 20% 40% 9 90 % do you work for frito-lay it's about 75% and the Institute of Medicine and a number of other organizations have suggested that our dietary intake of salt should be much closer to about 4 to 5 grams and for many people those rare people who happen to be over 45 obese black or have any form of insulin resistance or hypertension should probably be even lower which makes about 75% of the adult population so in any case we often talk about when we choose a solution to give which is the point of this slide I've gone off on a tangent but when we choose a solution we can choose from the extreme of 5% dextrose and water to what's called normal saline or 0.9% saline and we call it normal because it's of the same tonicity the same osmolality the same milli equivalents of plasma and so that's why we call it normal saline but you just told me that there were 9 grams of salt in a bag of saline so a very typical order that a house officer might write to a hospitalized patient of maintenance fluid at a hundred or 150 milliliters per hour would give a hospitalized patient up to three to four to five or more times the amount of salt that's recommended in terms of intake and that's in a hospital so if we talk about never events and things to avoid errors this is one of the things that we should be talking about about choosing the right fluids not only when we go home at night not on we're taking tests here but also in the hospital so we see that 5% dextrose is actually 50 grams of dextrose per liter there are 180 grams of dextrose per mole based on the molecular weight of dextrose and that comes out to two hundred and seven point two seven eight moles per liter or two hundred and seventy eight millimoles per liter and you recall that the tonicity of plasma I suggested to you was about 300 maybe 290 or so so this is pretty close so what this means is that if you give dextrose in water there's enough stuff in that bag that you're not going to run into any problems you're not going to cause an imbalance or irritate anything that might cause problems let me give you a scenario let's imagine that you didn't want to infuse 5% dextrose because you were on a diet and you didn't want those 50 grams of carbohydrate and you just wanted to give water and you just took sterile water and you infused it into the vein would that be okay how come you're right I mean that's a loaded question making it too easy for you I should have changed my tone come on that's great or something so what would happen well it would distribute would it distribute into the plasma or the extracellular space or the total body water total body water so you're getting your compartments all down that's excellent yes um no but we have a case about that at the end of the talk yeah will death so the I'm sorry so the question was if I could paraphrase you that well when I was in Chicago a marathon runner drank a lot of water at the end of a race and died is that what that's is and that's another really interesting topic and we're going to talk about that because that's important in terms of water balance but that's not the issue that I'm discussing now remember I told you about permeability of the membrane yeah no that's okay shame on you no you know it much much worse is I don't know if you heard about this but in Sacramento there was one of those you know crazy talk radio stations you know had a water-drinking contest and someone was killed you know marathon runner these things happen and I'll explain why and we'll learn about that and why that happens but just sheer stupidity and malice contributed to someone's death from a water-drinking contest but no that's different so we talked about permeability of membranes so what would happen if you infused water what would happen to the cells of the body exactly so would water go into the cells with the intracellular contents I showed you in that colored graph the potassium and other intracellular cations and ions with those would they leave the cell and probably not not in large quantities water would go inside because only things that are permeable would go inside so dextrose can exchange across that membrane water can exchange across that membrane but if there's just water alone and nothing no other stuff none of the awesomes then you could infuse water and it's been done by mistake often and the cells they burst and they burst because they swell because there's free permeability of water across the cellular membrane the cell then swells and this can cause major problems the typical problem that occurs is something called hemolysis where the red blood cells burst but all of the cells can burst and this can be very dangerous and one of the reasons why we're very nervous about water intoxication because it can cause cells swelling so we talked about this so this is just a picture of a cell and it highlights the fact that the osmolality inside the cell is about 280 290 and so if we started with 280 milli as moles in the plasma but rapidly infused pure water and we changed the osmolality so that there was more water outside the cells than inside the cells either the stuff has to leave the cells or the water goes into the cells and since the water is completely permeable and and travels across that membrane that's what happens in the cell bursts so we've already gone over this issue about normal saline and 0.9% and this gives you the answer of about what the plasma and blood are this is a typical person of 70 kilograms I don't know there aren't that many 70 kilogram people anymore we're all you know 85 or 90 kilograms yes your question well in this setting where where the water could theoretically be infused into the blood the blood cells are abundant in the vascular space so they would burst and that would mean that the contents of the blood cells would escape into the plasma the you know the non blood liquid and what you would see is staining of the plasma and you would you would you would probably cause some kidney problems because the hemoglobin inside the cells can be injurious to the to the kidneys but you would you would end up seeing basically a profound anemia because the red blood cells would burst this is not a very common it's not a very common issue but this issue of cell swelling in the setting of hypo osmolality is relevant to the marathon runner case and other issues and you know certain tissues can swell and can afford to swell a little bit red blood cell can afford to swell a little bit it can swell a lot the brain can swell a lot because it's in a closed space and you know I worship the kidneys but the brain the brain is supreme so you know if the brain is in a space and it can't expand and the brain is injured then all bets are off but this gives you a diagram of what the compartments look like about 60% of the body weight is in water I know we think about lettuce being about 98% water we're about 60% water and about as I alluded to earlier there's more intracellular water than extracellular water about two-thirds and one-third and within the extracellular water the interstitial space is roughly 6 litres in the average sized person the blood is about five liters or I'm sorry about nine liters and about five liters and the plasma is about three liters and the red blood cells account for about two liters which is maybe why the gentleman with the headphones in the second row said two liters because he knew that the blood cells were about two liters but in fact the blood itself is about five liters in a person of this size so this just gives you a general sense people argue about whether plasma and interstitial is 1/3 and 2/3 or 1/4 and 3/4 it depends on the body state there are certainly disease states where there's an excess of interstitial fluid that gets accumulated okay just a quiz most of the body water is outside of the cells or inside of the cells perfect so you you know it's like those debates on NPR you know you test them at the beginning you test them at the end and you're doing great boy the time is really flying okay so the standard 70 kilogram genderless teaching person contains about how many liters of extracellular fluid so seven deaky so calculated for me 70 kilos what percent is body water 60 so 70 60 percent of 70 is 42 and what percent of that is extracellular about 25 to 30 percent right so that's how you get to 15 and of those 15 liters of extracellular fluid roughly how much is plasma and roughly how much is interstitial about 5 and 10 so plasma and blood so the vascular space and the interstitial space okay a 70 kilogram person now will do this calculation I don't have a blackboard that's great so a 70 kilogram person has a plasma sodium concentration of 165 million spur liter so would we call that hypo or hyper natrium iya hypernatremia that's right so when the sodium concentration is high we call it hyper when the sodium concentration is low we call it hyponatremia normal sodium concentrations are generally about 140 but between maybe 138 and 143 or there abouts but for ease of calculation if you assume that the normal is 150 someone calculate how much water we would need to give in order to bring the sodium from 165 to 150 well so one way to calculate that would be to to determine and and this is one of the few formulas that I that I use regularly we're ok I can we can talk through it thank you really please you know all the tricks thank you so if we're trying to assess the the this would be a water deficit and this is a common calculation we do in the hospital forgive me I'll try to shout can you activate this mic here so if you take 165 and you subtract 150 that gives you 15 and you divide that by 150 so that's about a about a 10 percent water deficit and so the you know the easy way of calculating that would be if you know what the total expected body water which we said was about 42 liters it would be about a 4 liter water deficit now in truth in the clinical arena we often see hypernatremia it's very common very common on the medicine service at an adult hospital and we often have a lot more complicated calculations to make because often the patient's need a lot more water than what they simply need to correct this because there's usually something driving that that elevated sodium concentration one of the most common reasons for this to occur is very high blood glucose concentrations out of control diabetes which causes what's known as an osmotic diuresis that is there's a high level of an osmotically active compound that promotes water loss through the kidney so obviously people are of different size and distribution so we need to think about this the management of kids with balance disorders very different than the management of adults the management of lean adults is very different than the management of obese adults and there are a host of abnormalities where there's major excess in extracellular water what are known as the edema disorder z' which are basically three general disease states one is called congestive heart failure we usually call it heart failure but the traditional name is congestive heart failure reflecting pulmonary congestion associated with poor heart function either a poor squeeze or an inability for the heart to relax the second form of ademma disorder z' fluid accumulation looks like what this gentleman suffering from which is severe chronic liver disease with cirrhosis and does anybody know what the third and most important cause of edema is dr. pizza pardon me well yes either nephrotic syndrome protein losses and other forms of kidney disease kidney of course much more important than anything but the brain so let's let's let's talk a little bit about some more fine tuning balance and I will go over a couple of cases and then we'll leave some time for questions I think we're doing okay timewise so how do we maintain our sodium concentration in the face of drought or plenty so we know that the cells behave thank you so much for coming and for staying I hope you feel better so we know that water is freely permeable across the membranes we talked about that but how does the body maintain balance because I'm sure in a week any of you with a busy life will have periods of time when you're out in the Sun where you're on a long drive you have no access to water other times where you have plenty of access to water how do the victims of the Chilean or Haitian earthquake survive without water for so many days how is the body able to maintain that and there I'm going to talk with you about a couple of really exquisite hormones and I call them exquisite because they're just they're fine-tuned so beautifully and they help maintain this balance of electrolytes ADH or antidiuretic hormone is one such hormone goes by the name vasopressin it's also known to cause vasoconstriction that is constriction of the blood vessels it's a medication that squeezes the blood vessels or not a medically well it is a medication but it's a hormone it's now become a medication to help treat people with very low blood pressures in the hospital or antidiuretic hormone because it prevents the loss of water at the kidney level and it does so by acting at the collecting duct of the nephron if you recall your text there's a beautiful picture of the nephron I should have pasted it here it's a beautiful picture and it shows the it shows the glomerulus which is a tuft of capillaries these are tiny blood vessels that connect the arterial system and the venous system basically the filtering units of the kidney are made up of live blood vessels so the idea that we can try to come up with an artificial membrane this is an exquisite biological system and then there's something called you might have recall this picture it's much more beautifully depicted in your text but there's something called this is the glomerulus this is called Bowman's capsule and there's the the plasma is filtered and the proteins in the plasma in the blood and the plasma are generally retained dr. piezo mentioned a disease of the nephrotic syndrome where people spill protein in the urine and that can be problematic but what comes through this filtering mechanism is then basically a distillation of the plasma so the proteins and the blood and the important things that you don't want to lose are generally kept and then everything that's dissolved in the solute that's dissolved in the plasma water gets filtered and then it gets processed and it's really a magnificent system many of the this-- is called the proximal tubule this is the workhorse of the kidney this is where most of the important stuff that gets dissolved in the plasma water but we don't want to lose like amino acids so proteins are big and they don't pass through the filter but amino acids are small the building blocks of the protein are small I'm sorry and the amino acids are small dextrose is small the electrolytes are small so they go through the glomerulus they tend to be reabsorbed in the proximal tubule but then this filtrate which is sort of you might call it pre urine it's going to become the urine but the plasma filtrate goes through a series of processing steps where there are mechanisms to modify the concentration of materials within the filtrate so as to keep balance so among those is that the body reabsorbs sodium so what would happen if we didn't well boy if you get this I'll be so proud what would happen if the if the kidneys didn't reabsorb the sodium you'd have to eat even more salt imagine that yeah so what would happen is that whole extracellular space that whole extracellular water we've been talking about would be depleted including the interstitial space and the vascular space and what would happen if our vascular space were depleted of yeah it would be would be a little bit different than bleeding we would just become desiccated we our blood cells would stay in the blood vessels but all the other material and the blood vessels would come out so the blood vessels are 40% the the plasma is 40% blood and 60% other stuff including the filtrate which has an osmolality that's roughly what yeah excellent 300 so if we don't reabsorb most of our sodium in the in the kidney we would go into shock now what would happen if we didn't excrete any of our sodium what would happen if we ate a bag of Doritos but our you know every five minutes but our kidneys didn't eliminate sodium when we had sodium in excess exactly so we would swell up and our extracellular compartment would expand both the interstitial area and the vascular area so we'll see how boy you guys are really good so what would happen if the vascular space were to expand abruptly what would what might you see on a physical examination blood pressure I heard it excellent the blood pressure would go up what might you see if the interstitial the supporting tissue the infrastructure were to swell up what would you see edema who said edema raise your hand you must love the kidneys thank you right so the filtrate gets processed and it's really in this that's called the collecting duct where all of the fine tuning of water balance is held and there's this exquisite hormone called ADH or vasopressin that basically serves to allow water to be reabsorbed so if I'm an idiot and I go to some radio station in Sacramento and I drink a gallon of water do I want my kidneys to reabsorb that water or do I want my kidneys to excrete that water excrete that water exactly and so what happens to the color of your urine when you sleep overnight or hike in the summer heat does it get dark and okay so it gets darker and why is that and why is it concentrated what hormone is activated vasopressin - these guys are great fabulous what happens to the color of your urine when you drink eight glasses of water or a six-pack of beer it lightens so the ADH is suppressed exactly then we're going to get to your marathon case we're going to get there so ADH is produced in the posterior pituitary gland does anybody know where that gland resides it's in the brain right in the base of the brain in response to osmotic effects and so we've talked about that the higher the osmolality that results in an increase in ADH secretion so that the kidney tells a signal to the collecting duct cells okay open up the water channels let the water come in okay when the osmolality drops down and says shut off those water channels and don't let the water in let it go down the sink or down the toilet but interestingly their variety of pulmonary and central nervous system or lung and brain diseases that can also elicit increases in ADH which is something interesting we use such terrible terminology in medicine but it causes something called the syndrome of inappropriate ADH secretion or SIADH and also low pressure when the when the body has low blood pressure there's a receptor around it's called the carotid body it's up in the neck near the carotid arteries and it's a pressure sensor you know our bodies are fabulous they have so many kind of safety safety devices if only Toyota could you know good design cars that are as precise and have so many safety nets so why do you think the body would be designed in such a way that we would have baroreceptors that would activate ADH in the event of low blood pressure who said saber-tooth Tiger bite Thanks so what's your name apartment hi Cynthia thank you yeah saber-toothed Tigers play a big role in in medicine but they really do and we often use saber-toothed Tigers to describe hormonal responses that occur and the you may have heard I don't know what they had their endocrine lecture yeah okay well I'll take just a moment there's something called their two autonomic nervous systems two automatic nervous systems that work without the volitional control of our brain and those are the sympathetic nervous system which which modulates the fight-or-flight response that's the saber-tooth Tiger part and the other is the parasympathetic nervous system which is the mellow cool beary white nervous system so so the these when the sympathetic nervous system gets activated you know the kidneys are so smart they don't even need the brain to tell them what to do it's just automatic so when the sympathetic nervous system activates it causes a variety and causes a variety of hormonal responses and it turns out that what those hormonal responses do or tells the kidneys absorb all that sodium don't let the sodium go hold the sodium now you we've talked about this already you'd want to hold on to sodium if you were bitten by a saber-toothed tiger so who saves you when you're bitten by a saber-toothed tiger yeah I mean ultimately it's the kidneys your your adrenal gland save you because they produce the epinephrine or adrenaline so without the adrenal glands the kidneys would just you know be waiting and waiting and waiting but ultimately the kidneys save you because they prevent you from losing any more sodium you know assuming that you can get the blood you know the the blood the bleeding to stop so all those signals when they're shocked are to reabsorb sodium and we talked about this when we started that if we need to replenish the plasma volume we would give blood saline or water right and we said we would give blood if that were a preference or we would give saline that would be the best second choice because that's what goes to the extracellular fluid and it's more efficiently distributed into the plasma volume than something that gets distributed to the total body water so this you know pathetic little baroreceptor you know is just it doesn't know what to do other than you know it's it's sort of a safety net after the saber-toothed tiger induced sympathetic nervous system response which turns on all the sodium or tension and this baroreceptor is turning on ADH because you know when you're in a bind you know you want to absorb everything you can even though you want to absorb sodium for sure but you'll try to absorb water also so these are the two main pathological states where you see ADH in excess where there's lung disease or central nervous system disease or if there's low blood pressure okay and so I'm sorry question they're trying to wow so that's a great question I have to tell you in you know I'm not that old but in my in my 20 years or so of being a physician I've never never responded to a question quite like that so I've never heard of PMS described as a saber-toothed tiger buddy but I know well I have a twelve-year-old daughter so I know anyway so that's a really good question because that's you know one of those things in medicine and if you watch house you'll or you know you'll hear all these silly terms that we use in medicine you know it's really a language all of its own but we say oh that's true true and unrelated so they're true so PMS is a saber-toothed tiger true there's blood loss in PMS in with menses that's true there's fluid retention that's true they're true true and unrelated so just briefly the blood loss that typically occurs with menses is not massive so the kind of response the sympathetic overdrive massive you know fight-or-flight response occurs when there's massive blood loss or a massive trauma or stress and not to diminish menses or PMS for that matter but the blood loss is not of a sufficient volume to induce you know those mechanisms so the water weight relates to the effects of thee and these these are great I hope that you'll ask lots of these questions when we finish up because these are great questions the water accumulation or the fluid accumulation now I'm going to test you is that a vascular intracellular or interstitial fluid that accumulates around your menses it's interstitial but that's okay anyway the the the hormones the progestins mostly the progestins actually have it's very interesting the progestins are related to a another so the progestins are made by the ovary predominantly made in small quantities by the adrenal gland the adrenal gland also makes a variety of hormones the adrenal medulla makes epinephrine or adrenaline but the adrenal cortex makes glucocorticoids and mineralocorticoids you might say mineralocorticoids interesting minerals that sounds like what we've been talking about so there's a hormone known as aldosterone that's made in the adrenal cortex that promotes salt retention and the progestins that are in excess around the time of menses cross-react with some of the mineralocorticoid receptors and they actually cause sodium retention here in the distal the distal portion of the nephron so that's very common and that's because the kidneys now you can blame the kidneys for your fluid retention it's the kidneys fault so any other questions before I move on to another exquisite hormone yes question it's kind of piggybacking off what she was asking but when you are under stress if normal stress Express supposedly is related to a high blood pressure is related to stress is it is the stress of the high blood pressure causing this the sodium retention which is causing the high blood pressure wow that's a great question and a number of a number of the young scientists in our division are trying to understand the mechanism of hype of hypertension hypertension is incredible our high blood pressure hypertension is incredibly common and even after centuries of understanding a little bit about hypertension and decades of understanding a lot about hypertension we don't really know in all cases why why why it develops the you know the certainly I would say that a sort of continuous high stress situation with high levels of epinephrine would promote sodium reabsorption in the proximal tubules it would also promote diabetes and which diabetes can contribute to hypertension and other ways it can promote obesity it can promote sleep apnea it can promote a lot of stress can do a lot of bad things that can then interact and cause hypertension whether there's a big component of renal salt retention in the stress associated hypertension I'm not sure probably in some patients probably not in others it's a great question and I mean it speaks to how this is a really common disease and we don't quite really understand why is it for instance that when someone loses 10 pounds they can see a 20-point drop in their blood pressure we don't understand that incredibly common see your doctor doctor notices that your blood pressure sciences you really should lose a little weight perfectly reasonable sensible healthy recommendation what's the mechanism of that weight-loss one of one of our colleagues Vivek Bala hope he doesn't hear this or see this but he's submitting some grants to try to study the association between obesity and hypertension understanding the molecular mechanism using mice and knockout mice and things like that any other questions before we go to exquisite hormone number two and there are a whole host of hormones I don't want to you know I don't want to diminish any of the endocrine discussions that you'll have but this is really more about electrolytes so they can talk about diabetes and other things but there's something called parathyroid hormone which is a great source of confusion because it has nothing to do with the thyroid everybody knows about the thyroid where is the thyroid located in the neck so where is the parathyroid located around or near the thyroid and that's why it's called parathyroid but it has nothing at all to do with the thyroid that terrible confusion terribly I'm there for glands look located atop the thyroid they're responsible for maintaining stable ionized calcium concentrations which are important to the function of all living cells so we've talked a lot about sodium and water a little bit about potassium we haven't talked about calcium calcium is another one of the really important electrolytes that our body keeps within a very very very narrow range parathyroid hormone also helps to maintain serum phosphorus concentrations by modulating the kidneys handling of phosphorus and this is again another story of you know like we talked about with the water you know in the desert or in plenty our kidneys have to manage a completely varying environment varying diet the kidneys and the liver too that you know that matter have to manage vast differences and imagine what we were like before we had you know grazing eating behaviors when we would you know be food less for several days and then we'd feast on a beast and we'd have you know zero phosphorus intake for three days and then we'd have an enormous amount of phosphorus intake for three hours how do we maintain phosphorus balance in the state of that and the fact that our kidneys can do that you know aren't have you been convinced that the kidneys are the smartest organs after the brain so phosphorus you know just to spend a minute because it's a couple of my friends are looking toward getting the the FDA to have phosphorus labeled on on foodstuffs because it isn't and for people with kidney disease it really matters but it's an important component of bone basically calcium and phosphorus are important components of bone mineralization it's also an important component of ATP or adenosine triphosphate which is the molecule that's responsible for energy metabolism in cells so basically you need phosphorus about as much as you need all these other important things I've talked to you about its present in the diet mostly in protein sources and especially in dairy products so I'm sure you've all heard people talk about drink milk it's good for your bones well it's not only the calcium it's also because there's phosphorus yes question yes it's a very interesting question also there is phosphorus in Cola drinks and so for someone like most of us in the audience I presume who have ample kidney function there's really no consequence in terms of the phosphorus for someone with kidney disease who has impaired phosphorus excretion there could be consequences and since this is a non new totally non-nutritive source of phosphorus it would be a shame for someone who has to restrict his or her phosphorus intake to well you have to think about what are you know what you're taking in and also what you're taking know what you're not taking in as a result of what you're taking in so one of the one of the major controversies is whether juices sodas other things should be supplemented with vitamins or calcium or other things that children used to drink and if children don't drink milk which they need for you know what else does milk have aside from calcium and phosphorus anybody know lots of vitamins lots of protein lots of vitamin D and everyone's deficient in vitamin D at least in San Francisco they are maybe less so in Palo Alto maybe I should move well you know milk for someone whose electrolyte depleted milk is the simplest and probably most elegant replacement fluid so if you see someone who's really depleted in many ways say someone in the hospital with you know who's just been washed out say has had nothing but alcohol for the last you know a couple of weeks milk has a lot of sodium a lot of potassium a lot of phosphorus calcium magnesium protein vitamin D it's a magnificent food source but so if teenage girls who are in the midst of their their greatest period of bone growth don't drink milk and they don't get phosphorus adequate phosphorus and calcium they don't mineralize their bone as well when they become postmenopausal women they're the first ones who develop osteoporosis so I think it's extremely important for children and adolescents and young adults who are still growing bone to not drink too much of this because and they're not drinking other things that have other good stuff for cans is there's a lot of caffeine in there too okay so let's do two illustrative cases before we'll break for questions we're doing okay timewise so a 32 year old female engineer and I didn't know you were going to raise this question with no past medical history decides to train for the Boston Marathon she completes most of the race with relatively little difficulty but she injured her ankle at Mile 24 she completes the marathon and rehydrates after the finish line she feels well but develops a headache on the trip home her partner finds her barely responsible barely responsible barely responsive at 11:00 p.m. hopefully responsible she was hospitalized at Sequoia hospital and develops a coma and we don't want to talk about anyone getting a coma at Stanford so so her serum sodium concentration upon admission was 170 107 millimolar liter if you needed one word to describe that what word would you use hypo Wat hyponatremia excellent and the head CT the head computed tomography or the imaging of the head shows diffuse brain swelling now you guys are so smart why is the brain swollen so so too much water and well not enough sodium in the extracellular space too much water in the extracellular space permeable membranes and transfer of water from the extracellular space to the intracellular space leading to cell swelling and she requires intubation and mechanical ventilation meaning she basically was comatose so why was the sodium 107 so she sweated a lot lost some water okay and why else she drank water sodium went out in the sweat so you know that's a good hypothesis that's a that's a great hypothesis it's a great hypothesis but you don't lose that much you know you don't lose in terms of the amount of sodium in our body and in our plasma volume you don't lose that much salt when you sweat you do lose salt but you're actually losing a lot of water when you sweat more water than salt you do lose a little bit of salt when you sweat that has made our colleagues at the University of Florida Florida in the division of Nephrology they have the largest endowment for nephrology related research because of the development of Gatorade because people really you know water is actually pretty perfect to hydrate hydrating solution Gatorade tastes good and some people do cramp less and feel better but water is pretty good so but why did the sodium get to 107 someone said ankle and so she injured her ankle and well that's that's another good hypothesis that might have happened so if for instance she went into shock after her after her marathon or her blood pressure were very low she could have had activation of her baroreceptors and then she would have had an enhanced antidiuretic hormone so all as she was rehydrating she would have reabsorbed more water in her what's this called again collecting duct right so she would have absorbed more water that's possible but it's probably more likely back to the other question which ties in back to the we said lung or CNS or central nervous system disease and I think anyone would say that completing a marathon would be a pretty massive stress and injuring ones ankle at Mile 24 of a marathon and completing another two and a half miles with an injured ankle would be an intense stress I can guarantee you that in about 12 seconds my other phone in my other pockets gonna ring even though I told my wife and kids that I had a lecture to give tonight so so either brain injury or stress severe stress or lung disease can cause this syndrome of inappropriate ADH secretion ADH gets activated and there's an overshooting so that when she rehydrates with water she dilutes her body and probably the only way we could have figured that out as if someone were watching her to see if she were urinating now this we don't do experiments on medical students anymore it's a very good thing dr. piso is left left the room but you know years ago I was told by a nephrologist who was conducting experiments on water balance that he was doing water infusion studies that is giving dextrose and water not plain sterile water we talked about why but dextrose in water and to see what the body's response would be and how much the sodium would drop and how dilute the urine could get under certain circumstances and what he noticed was that there were a few medical students who were in the the general Clinical Research Center who God's excuse me got so nervous when they were being stuck with a needle that their very ample urinary output shut down and so it shut down because the urine which was dilute then that pre you're in that filtrate got reabsorbed and that was a sign that there was inappropriate ADH secretion because that water was getting absorbed and not excreted so why so we talked about why was the brain swollen what might happen if this is not corrected quickly part of me so the cells so cell bursting could occur but cell swelling is likely to occur in the brain the cells don't burst the way blood cells burst but if the brain swells in a closed cavity that's a real problem so the worst thing that can happen is something called herniation where the brain swells and because it can't move anywhere but out it basically slides out the what's the it slides out the foramen in the neck and it so happens that the portion of the brain that's near the spinal cord includes and my wife is a neurologist so I can talk a little bit about this because I don't know Anatomy or neuroanatomy I hope none of the neurosurgeons or neuroanatomists are listening but the portions of the brain that are responsible for some of the vital functions come from the most primitive portions of the brain the midbrain the pons and those are the portions of the brain that get basically squashed as the brain just swells and exits out the back it's not the cortex which is the thinking part but the breathing vital organs part and people can die from brain swelling and that's what probably happened to this marathoner in Chicago and that's what happened to the woman who drank I think it was a woman I don't recall who who won the water or was participating in the water drinking contest now why would it turned out that the woman in the water drinking contest who died wasn't the winner she didn't drink the most water so tell me two reasons why the woman who didn't give me two possible reasons for why the woman who who drank the most water wasn't the one who died you guys are good so that's yeah so a bigger person is going to be able to dilute that extra water in a larger total body water space so the concentration of sodium is going to drop less than in a petite person and the other issue is people may have differential responses someone might get nauseated or might be nervous or might be excited because some you know radio host is going to give them tickets to a concert or something you know idiotic if they drink more fluids and so it could be either body size or the body and the brains response in the ADH status at the time so how might you treat her using what you've learned tonight how might you try to rescue her let's say her brain is swollen she's really confused she doesn't feel well but she's not comatose she isn't died she hasn't herniated how might you treat her part of me so yeah that would be one way so one thing that you could do you could give saline solution the normal saline another thing that you might do because this is such an extreme circumstances that you could give what's known as hypertonic saline you could give an even more concentrated saline solution because that would correct the imbalance faster it might cause high blood pressure but you know that's a limited consequence when your brain is about to slide out the back of the head so you might give hypertonic saline you might try to give something that would block the effects of ADH a medication perhaps if it were a chronic problem and these levels of serum sodium can develop chronically in people and not acutely like in the case of a marathon runner and and it turns out that we don't want to correct them abruptly if they've developed their condition slowly and sometimes all we need to do is restrict the water intake and let it correct gradually on its own so any of those things are possible therapeutic options so that was a good case let's talk just before we close about what's what I what I might call what used to be called renal osteodystrophy and this is shows you how intricate some of the balanced balances are and how important the kidneys are because when the kidneys aren't working things can get out of balance and quick so let's imagine a 67 year old man with diabetes mellitus and progressive chronic kidney disease he has a serum creatinine of three point seven milligram per deciliter I give you the reference range for the population of 0.7 to 1.1 that basically tells you that his glomerular filtration rate this is the glomerulus the filter though the rate which is the amount of filtrate that gets filtered per min / some corrected body size is about 19 MLS per minute normal turns out to be about 120 and if you think about this for a minute how spectacular the kidneys are they filter about 180 litres of blood per day okay so we talk today about what the volume this brings everything together but the volume of the blood is so 180 liters per day maybe four and a half liters of blood that'll open I'm getting all these calls and texts this is crazy so anyone anybody want to calculate that one 180 divided by four point five nice round number forty so that means that our blood is filtered in a day forty times by our kidneys if the kidneys are normal and the body is so exquisite that we can live well and healthfully with as I suggested to dr. piso earlier just a fraction of a fraction of one kidney we have a lot of redundancy in the system but the kidneys must be really important if they filter the blood 40 times a day I think there are things about the kidney that many many many things about the kidney we don't have a clue kidneys are probably contributing to a lot of things that we don't appreciate we kind of think of them as you know waste management systems but they probably die when we know they do a lot of other things they modulate the immune system they may attenuate the inflammatory process people with kidney disease experience a whole host of diseases that some of which we understand well some of which we don't having healthy kidneys is really important this gentleman does not have healthy kidneys he also happens to have hypertension high blood pressure hypercholesterolemia and peripheral arterial disease meaning cell claudication or problems with circulation of the lower extremities he also has a serum phosphorous of six point three milligrams per deciliter which is elevated and a serum calcium of eight point one milligram per deciliter which is low and the parathyroid hormone those four glands atop the thyroid is eight hundred and seventy-three picogram per milliliter so it's more than ten times the upper limit of the population reference range so what do you think is happening here kidneys aren't working very well and so so what what glands are trying their darndest to help the kidneys in that state the parathyroid gland is helping it's trying really hard the phosphorus is high person's eating but the phosphorus is high so the kidneys have lost their capacity to maintain phosphorus balance and so a safe - another safety mechanism has come into place which is the parathyroid hormone level which is trying to get the kidney to get rid of that extra phosphorus which is accumulating that tells us something not only is sodium important and potassium important and calcium is important but phosphorus must be important too because if the body is so unhappy at having a high phosphorus that it pushes these glands to go into overdrive what happens with too much phosphorus well it can deposit in bad places so the patient then complains a bone and joint pain and muscle weakness because the parathyroid hormone is affecting the bones and the joints he develops a foot ulcer which is a very sign in someone with diabetes and chronic infection and an angiogram or a imaging study shows calcific arteriosclerosis meaning that the blood vessels are calcified so one of the consequences of high phosphorus is that it can basically it's very interesting if you look at it can basically produce bone in the blood vessels if you look at an x-ray of a patient who has advanced kidney disease you can basically see an outline of the aorta the main artery supplying the body because the blood vessel wall is full of bone that's pretty scary so the question is what's out of balance well the phosphorus and the calcium are out of balance and how might we try to correct these metabolic abnormalities so we now have a problem the body wasn't designed to develop kidney failure and when we were running from saber-toothed Tigers we weren't dealing with dialysis and transplant so we have this problem of distro 'fuck or misplaced calcification it's not going in the bones it's going in the blood vessels how do we try to treat that there are now three or four things are out of balance any ideas think logically think about your pantry think about what we've talked about since the start of the evening part of me less processed food well if that processed food is let's process food if that processed food is cheese whiz or sometng whether you can tell I'm I went to college in Philadelphia no one knows about cheese whiz in San Francisco it doesn't exist here it's been outlawed but yeah it's something that's high in phosphorus you try to reduce your intake of something high in phosphorus so as to reduce the workload of the kidneys to try to get rid of the phosphorus make it a little bit easier so that would be one thing that you might try to do just take in less phosphorus there's a limit to your dietary restriction because phosphorus is in a lot of foods but you could quit drinking soda you could quit drinking eating ice cream tastes good but it has very little nutritional value you can stop eating cheese anything else that you might try think how many of you are engineers we live in like the engineering capital of the world so I want an engineer to tell me another way that we could help correct these metabolic abnormalities no that's too easy and actually that doesn't work that well interestingly enough for phosphorus think creatively drink more how would that help yeah and so drinking more wouldn't improve the the way the kidney gets rid of phosphorus I don't think that would help very interesting so what absorbs what's responsible for phosphorus absorption so I'm going to help you there so you how about how about interrupting phosphorus absorption how might you do that so you're you're in a case of beer I don't think a case of beer might make you not care about your phosphorus so there is no real anti phosphorus unless I'm not sure what you're talking about in a phosphorous or what you mean but well you could if phosphorus is being absorbed from food how about interrupting the absorption of phosphorus so you might do something for instance that could that's a good hypothesis that might coat the stomach or the intestinal tract help prevent the absorption of phosphorus there turns out that the absorption of phosphorus is is an active process and you could inhibit the channels and the processes that absorb phosphorus or you could do something much simpler which is just bind up the phosphorus so take something with your food that soaks up the phosphorus and lets it go out in the stool before it ever goes into the bloodstream that's a very simple crude it's called they're called phosphate binders and they're a very important component of our treatment of people with advanced kidney disease and so foz let me just you know just to give you so my friend the stress lady yes Ubik what I'm referring to my friend as the stress lady because she asked question about dress types of foods actually as opposed to medication hmm possibly but with great difficulty so phosphorus I will tell you is negatively charged so right so you might take something that's positively charged and there there are several positively charged binders that we use the types of binders don't matter so much but you can take something that's positively charged that will bind to the phosphorous you then eliminate the phosphorus in the blood stream it doesn't get absorbed that's one way of helping correct the metabolic abnormalities another way would be to figure out something that would help improve the kidney function that's a tough one here because it's very advanced and diabetes related kidney disease tends to be progressive or you could do something like dialysis or hemofiltration yes well calcium calcium or calcium salts are effective phosphate binders aluminum salts are effective phosphate binders there's a AAA and rare-earth metal known as lanthanum which is basically what they wrap your cable wire with but there's a medication that's made out of lanthanum if you would like to try that can write you a prescription anyway this is you know we care for 350,000 patients in the United States who have n stage renal disease and are on dialysis and another 150,000 people or so with end-stage renal disease who have functional transplants and I can tell you that dialysis is a marvelous life-saving therapy but it sustains life it does not restore health let me tell you a figure which is very disturbing there are over a hundred thousand new 100,000 persons in the United States each year who start dialysis now what does that tell you pardon me well so that says so my friend from Chicago says that we'll probably have a large fraction of the population on dialysis and you would be correct if we could just get it right if we could actually restore people's health and sustain their life not for one or two or three or four years but for a long time so the problem is if a hundred plus thousand people start dialysis each year but the prevalent population of people on dialysis is only 350,000 that's telling you that a large fraction of those patients are dying every year and I bet you you know I've been pretty light hearted today and been chatting and having jokes and teasing dr. piezo and everything but you know this is serious business and when the kidneys aren't working well it's a pretty horrible disease mortality rates for people with end-stage kidney disease exceed those of people with metastatic prostate cancer breast cancer colon cancer AIDS it's not quite as bad as leukemia but it's about 20% per year in the United States so one in five patients who are on dialysis will die each year and the we're at a point now where the life expectancy of most patients on dialysis does not exceed the waiting time for a kidney transplant so even if people you know more often than not people will die before they ever get a chance to get a kidney transplant so a couple of parting messages if any of you if any of you have any relatives or friends with kidney disease it's serious business and if any of you want to help increase the public knowledge about kidney disease there are a lot of a lot of very active public organizations the National Kidney Foundation the American Association of kidney patients the American kidney fund we're much smaller than the American Heart Association or the National Cancer Society but this is a you know a very very severe disease it tends to affect a kidney failure meaning it tends to affect racial and ethnic minorities disproportionately blacks account for roughly thirty to thirty five percent of patients on dialysis but only about thirteen percent of the u.s. population so hugely disproportionate fraction of African Americans and other black Americans on dialysis and in our region also what's also very relevant is that Asians and Pacific Islanders American Indians South Asians from the Indian subcontinent and and Latinos are also at increased risk for progressive kidney disease so it's very serious business if any of you have any friends who would like to to endow an institute for kidney disease research I'm sure that dr. Gilliam and I can talk with you about that after the after the meeting you have a question up Tom well so those are those are that's a really good question when I said we have to get it right I mean we have to get dialysis right because what we're basically doing is we're I think again speaks to how exquisite and magnificent the kidneys are because we're doing a lot with dialysis of what we understand the kidneys to do yet people feel poorly and have foreshortened life expectancy so there must be a whole host of other good healthy things that healthy kidneys do that keep people healthy and alive that we just haven't figured out with dialysis because our membranes don't know they're not living membranes so I think you're alluding to the fact that prevention would be the best treatment so avoiding uncontrolled diabetes and uncontrolled hypertension would be important if there's a family history of kidney disease investigating that and understanding that and trying to understand rarer causes of kidney disease and you know mo fortunately most of the other healthy lifestyle recommendations tend to work and prevent kidney disease and kidney disease progression the irony of it is that the better and better we get at treating cardiovascular disease and I see a number of people in the audience older than I who probably remember either their generation or the generation proceeding when men dying in their 50s of a heart attack was not uncommon happened all the time that doesn't happen very often now because our therapies for cardiovascular disease are so much better I'll finish in a sec um but but the longer we keep people alive and they don't die from their heart attacks and their heart failure particularly with progressive diabetes they may develop kidney disease and so all of our therapies that we're prescribing to try to slow progression of kidney disease and reduce the number of people who end up on dialysis may be so successful at extending their life that they may end up gaining dialysis in the future rather than you know falling prey to their cardiovascular disease I'll let dr. Gilliam tell me if we can take any other questions first thank you for more please visit us at stanford.edu

Channel: Stanford

Views: 43,341

Rating: 4.8775511 out of 5

Keywords: Science, biology, kidney, health, nephron, cells, extracellular fluid, electrolytes, homeostasis, electro-neutrality, osmotic neutrality, intracellular fluid, interstitial, plasma, potassium, sodium, ions, anions, chloride, saline, body water, dialysis

Id: TMXsUYBXaZw

Length: 112min 20sec (6740 seconds)

Published: Wed Jun 09 2010

Reddit Comments

[u/easilypersuadedsquid]

(March 2, 2010) Dr. Glenn Chertow, Professor of Medicine and Chief of the Division of Nephrology at Stanford, discusses the functions of the kidney in organizing the body's systems.

Stanford Mini Med School is a series arranged and directed by Stanford's School of Medicine, and presented by the Stanford Continuing Studies program. Featuring more than thirty distinguished, faculty, scientists and physicians from Stanford's medical school, the series offers students a dynamic introduction to the world of human biology, health and disease, and the groundbreaking changes taking place in medical research and health care.