Experimental Calculations of Renal Function (Part 1)

00:02 This graph is quite important. We are going to dissect this in great detail. This information sometimes goes unnoticed and at some point when a medical student or resident or doctor whatever is posed with such questions, they have no idea how to interpret this. Learn it now so that you will never be confused. So let set this up and this exactly what is taking place in your body. I love this graph and you shall as well by the time it were done. Why? Well let us take a look. On the X axis, you have your plasma concentration of a particular substance and there is many here. We have para aminohippuric acid(PAH), we have inulin here, we have creatinine here and glucose. So those are the major ones that we will compare and as we go from left to right it means that the plasma concentration of that substance is increasing. Stop there. Understand that. Good. Next, on the Y axis, we have clearance. You tell me what clearance means. Did it get filtered? It did but that is the different definition.

01:06 What gets filtered might be modified? What do I mean by modification? Go into the PCT, meet me there, good.

01:15 Shake hands in the PCT, excellent. welcome. Next then what kind of modification processes could take place in the PCT. Reabsorption, what is happening? Removing your substance out of your urine lumen into the blood meaning always reabsorbing into the blood.

01:36 Secretion is the second modifiable issue and that means you are going into the lumen correct.

01:41 So that is a modification. Depending on the characteristics of the substances, the PAH, inulin creatinine, glucose, then you will have certain changes that will take place with clearance.

01:55 You tell me. Tell me about creatinine already. With creatinine, you will get slightly secreted.

02:01 So, therefore, you will have your clearance which is greater than GFR. We have discussed this a few times. We are going to bring this into play. So now on the Y axis, let us say we have normal GFR or add approximately. Take a look at the Y axis. Right along 100. We are hovering around there and as a surrogate marker, we will be using creatinine as being an assessment of your GFR and so we will be right around that range and we will see that as being shaded between let us say 100-120 because that will be normal of GFR. So let us talk about each one of these substances and you will find this to be fascinating. Let us go to the one you are all quite familiar with and then what I will talk to you about will be PAH and that gets a little tricky, but still doable, very, must be. Let us begin with glucose.

02:55 So where is this? While we talk about clearance. Initially, as we take a look at glucose, which is the green line on the X axis, we have plasma concentration increasing, increasing, increasing from left to right, but Dr. Raj I see that line being at 0 for a certain period of time for clearance. Why is that? Whats clearance mean? It is the amount of glucose that you are getting rid of. There is no pathology here. So therefore normally speaking when you have glucose in your plasma, does it get filtered? Yes, it does, right? And then in the PCT, how much of your glucose or what kind of modifiable factors taking place in the PCT. Is it reabsorption or is the secretion into the urine. What is it? Should you normally have right now? Normally speaking when you urinate and you did dipstick for glucose, should you find glucose in urine.

03:57 Of course not and if you have diabetes mellitus, then I don't know what your situation is but you get at my point. Normally you should never find glucose because it is always being reabsorbed. Thus for a certain period of time, you will notice for glucose, the green line that it is at zero. But now the plasma concentration is increasing, you tell me about your patient. Your patient is developing hyperglycemia. So, therefore, there is diabetes mellitus now. Then all of a sudden, we will talk about this in greater detail is the fact that you start hitting renal threshold. What does renal threshold mean? It is one of the first signs of your glucose that is appearing in your urine. So from the first time that you find your glucose appearing in the urine. Do not confuse the threshold with Tmax and these are things that you have seen in physiology and if you are weak there, then I would recommend that you review that so that you can work with me in pathology. So here you have had a threshold. Now you see that green line increasing, increasing and doing what? Increasing on the Y axis, which is what clearance. So now you are finding a little bit more glucose, little bit more glucose, little bit more glucose in the urine and as you do so, you find that you have glucose, which is increasing in plasma concentration so much so and you might have hit now Tmax let us say 370 and it is getting very close to normal GFR. But but but your next question and I am just going to ask it to you here. So you start pondering it and when the time is right, I am going to elaborate on this because right now it is about giving an idea of this graph. Why is it that glucose in that line no matter how high your plasma concentration in glucose gets. It is always going to be below GFR. Clearance of glucose is always going to be little less than GFR. Why is that? If you are able to answer that question right now, you are in fantastic shape, but if you are not that is okay. I like to tease a little bit as you know and at this point it's just so that you understand this graph. Your question at this point is even with the glucose level being at 370 with all these glucose being in the urine, it is still going to be less than GFR. Amazing, why? Because we could talk about this glucose transport and everyone does a glucose transport as in PCT. It is still trying to rebasorb. They are not damaged. Stop there. We have talked about glucose and we talked about creatinine and well there you have your inulin and that inulin there is whatever is GFR is pretty much equal to clearance. So therefore as inulin is filtered as it goes to the PCT none of it is reabsorbed, none of it is secreted. Whatever is filtered is cleared. So, therefore, inulin is the perfect theoretical substance. Do not confuse the inulin that is not saying insulin. That is not a type of inulin. Inulin is the perfect measure of GFR. So, therefore, clearance in GFR will be the same. Are you loving this graph? A lot of information. A lot of integration which you are doing this. Finally, we have PAH, para-aminohippuric acid. Walk me through PAH. What do you know about PAH? It measures you tell me. Use the P to advantage or PF, renal plasma flow is what it equals. Now remember from physio, what normal renal plasma flow is? It is 600. I want you to begin at the afferent arteriole. You are at 600 renal plasma flow. What is your filtration fraction. Twenty percent. So I've taken up 120 from 600. What are you left with? 480.

07:55 Where is that 480 remaining? In the efferent arteriole. Are we clear? You understand how important terminology is here and I know it it's intense, but lets walk through this likely you can pause me for a second. Take a breath and then continue. So here is your 600 and you have 120 filtration fraction, you are left with 480 in the efferent arteriole and what are you going to use PAH for? Using PAH to measure renal plasma flow. If everything is perfectly normal, then what should your measurement of para-aminohippuric acid be for renal plasma flow? 600. Dr. Raj how in the world am i going to use PAH as a measurement from the urine to measure renal plasma flow. How am I going to do that or how are you going to do that? What is the physiologic process? Because as we get into the peritubular capillary, are you there now? What must you do for every single one of those PAH so that when you measure the PAH in the urine, it tells you oh! renal plasma flows is 600 in this normal patient.

09:02 Every single para-aminohippuric acid or hippurate must be secreted into the urine so thus, we do find it, that it's measuring renal plasma flow of 600. I want you to now come to point 0 for PAH. At PAH, plasma concentration is quite low and the red line there for a certain amount where plasma concentration of PAH is at very very low levels. Zero slightly increasing. For lower levels of para-aminohippuric acid or hippurate, it is going to be completely secreted thus giving you renal plasma of 600. Dr. Raj why is it that PAH is not decreasing? Why is it that the clearance of it is decreasing? Well, this is a question that you will get.

09:50 There is an experiment in which you had a bunch of students that were injecting in mouse with tons of PAH. When PAH is in abundance, and plasma concentration is ridiculously high. I want you to go all way to the right side and I want to take a look at the red line. It is almost equal to your GFR and that is what happens physiologically. When an increase in plasma concentration of para-aminohippuric acid to the umpteen or extreme level, it will almost equal GFR. But at low levels, it is almost perfectly equal to 600. You have understood that much right now and if any point of time, you have a little bit of a question either get back to me or review your physio because I need you to know at least this much so that I can feel comfortable walking you through some important pathologies that are going to come in dealing with glucose, dealing with creatinine.

10:48 Renal blood flow, what is it? It is renal plasma flow plus your nonplasma blood. What is your plasma? Your plasma is going to be minus RBCs and it has many many many alveolar coagulation factors and it has proteins. What are you going to use to measure renal plasma flow? Para-aminohippuric acid. At what plasma concentration concept? Low plasma concentration of PAH gives you a perfect approximation of renal plasma flow. What is renal blood flow? It is renal plasma flow/(1-hematocrit). You tell me what normal hematocrit is approximate.

11:25 Use 40, You will be fine. What is hematocrit? You take a test tube. You do a centrifuge and what ends up at the bottom. What would be the concentration or percentage of your RBC? The sediment. So what is renal plasma flow? We just got then talking about this. Clearance of substance completely cleared by a single pass. Welcome to PAH. Talk about that filtration fraction. Guess what we're going to do. We're going to use that clearance formula. Remember what that was? ultraviolet over P, UV/P. So before we begin, though, close your eyes. What is filtration fraction? GFR/RPF. Stop there. You tell me. What is the perfect measurement theoretically, physiologically for GFR? Perfect. Inulin. What do you use clinically? Creatinine. Are we clear? You as a doctor, you as a clinician, will use plasma creatinine to measure kidney function or to measure GFR. Now physiologically you might get questions in which you want to use inulin. That is the perfect theoretical substance. So if we are going to use GFR and we are going to use inulin, take a look at filtration fraction and it is equal to the clearance of what substance? Inulin. Stop there. Now we have RPF. What did you and I just talk about as being a good measurement for renal plasma flow? PAH and with this take a look at the denomintor. RPF clearance of renal plasma flow or excuse me, para-aminohippuric acid.

13:09 What do you do next? If you were given information with that clearance, what is the equation for clearance? UV/P. So what are you going to do for GFR? You are going to take a look at step by step. Urine concentration of whom. Inulin x flow rate UV/P. Plasma concentration of whom? Inulin because what we are measuring? GFR. It would be the same concept for clearance of para-aminohippuric acid. What is the normal filtration fraction? 15 to 20 percent, you will be fine to use 20 percent.