 Renal clearance is a concept which is used to estimate glomerular filtration rate and renal plasma flow. Clearance of a substance is defined as volume of plasma that is cleared of that substance per minute. But what is the meaning of this? That is volume of plasma which is completely cleared. Does that actually happen? See we will understand it by taking one example. Say suppose we have 10 ml of plasma some arbitrary numbers we will take. So 10 ml of plasma and in this 10 ml say suppose 10 milligram of a substance is present. So concentration of the substance will be 10 milligram in 10 ml that is 1 milligram per ml. Is that it? Now say suppose 4 milligram of substance is excreted in urine. So how much substance will be left? Basically 6 mg will be left. So this 6 mg will now be present in 10 ml of the plasma. So now the concentration becomes 6 milligram in 10 ml. So that means the 6 milligram entirely will be distributed in the entire 10 ml something like this. But we are telling that clearance is basically plasma volume which is completely cleared. So instead of looking it like this what we can say that say suppose this 10 ml is there then we can say that this 6 mg which is left because 4 mg has been excreted. This 6 mg is present in actually 6 ml of plasma that is the concentration will be same 1 milligram per ml. And this 4 ml of plasma is now completely cleared. Understanding? So this is just another way of looking at it. In this method of looking we are saying that the concentration of the substance has decreased. So in 10 ml only 6 mg is present. But in this example in which we are explaining the definition of the clearance plasma volume cleared then we can say that okay the 6 mg is present in 6 ml of plasma and 4 ml is completely cleared. Okay so if we determine clearance rate of substances we can actually use that clearance rate to determine GFR and renal plasma flow. So how is this clearance rate determined? So to understand this let's take an example. Say the plasma concentration of a substance is 10 mg in 100 ml of plasma that is if we calculate it it will come to 0.1 milligram per ml of the plasma. And say amount of substance excreted in urine per minute is 2 mg per minute. Now this amount which is excreted in urine per minute can also be written as like this that is concentration of the substance in urine into volume of the urine per minute that is known as the flow rate of urine. Because see we know that mass is equal to concentration into volume. So this amount we can mention like this also. So we know that in plasma 0.1 milligram of substance is present in 1 ml of plasma and we are saying that 2 milligram of the substance is lost in urine per minute. So if we find out that this 2 milligram was present in how much amount of plasma we can say that okay that much amount of plasma has been cleared of that substance isn't it? So that we can calculate by simple math that if 0.1 mg was present in 1 ml of plasma 2 mg will be present in this month's plasma which is being cleared per minute. So this is the logic of it and we can derive the formula also by this that clearance rate of a substance see this 2 milligram per minute we have already mentioned as concentration of the substance in urine into flow rate of the urine and this portion if you see this is nothing but the plasma concentration of the substance. So this is inverse isn't it? So plasma concentration of the substance is the denominator. So this is the formula for the clearance but one thing you should be very clear that for using this concept this formula for clearance the substance which we are using for determining the clearance it should be freely filtered in the tibules. So this term is very important freely filtered meaning see whatever concentration is there in plasma same concentration of the substance should be in the tubular filtrate okay. Now to understand that which substance is used for glomerular filtration rate and renal plasma flow let's take three scenarios okay. So plasma concentration of a substance is say 1 milligram per ml and we suppose that 125 ml of plasma is getting filtered in the tibules per minute. We have three scenarios in one 125 milligram of substance is excreted per minute now you see that since the plasma concentration is of the substance is 1 milligram per ml so if 125 milligram of substance is excreted that means 125 ml of plasma is getting cleared of the substance. In the second scenario 120 milligram of substance is excreted per minute that is lesser isn't it? So it is only 120 ml of plasma is getting cleared of the substance. So 125 ml is being filtered which is carrying 125 mg of the substance with it within the tubules but in the second scenario lesser substance is getting excreted per minute. So obviously the plasma cleared is also less with the concept which we have discussed you know. In the third scenario 130 mg of substance is being excreted that is more substance is being excreted per minute than that which is getting filtered. So that means more plasma is also getting cleared that is 130 ml right? So if you see that in the first one basically the clearance of the plasma is same as that of the normal filtration rate that means whatever substance is getting filtered that is being excreted. It is neither being secreted into the tibules nor it is being reabsorbed. So you see any substance which follows this can be used for the estimation of the plumbler filtration rate. In the second one actually this lesser amount of substance is being excreted that means filtered was 125 mg but excreted is lesser so that means some amount of the substance has been reabsorbed in the tibules. In the third one if you see more substance is being excreted that means the substance has been secreted in the tibules. So this third kind of substance is used for estimation of the renal plasma flow. How that we will see little bit later this needs a little detailing. Okay so what is the substance which is used for estimation of GFR? So that substance should be non-toxic obviously should be freely filtered any substance should be freely filtered that I already told and it should be neither secreted nor reabsorbed because if it is secreted it will give a higher value if it is reabsorbed it will give a lower value of GFR. So once a substance is inulin or which is used for estimation of the GFR but inulin is not a natural substance so it needs to be injected into the body but apart from inulin there is another substance creatinine which is used clinically because actually this is physiologically produced in body since it is a byproduct of muscle metabolism and mostly its excretion is only dependent on GFR so that is the one which is clinically used for estimation of GFR. However there is some secretion in the tibules also for creatinine so that means it will give a higher estimate of GFR but the error which is there in calculation the estimation of the creatinine that there is some error in estimation so that cancel out this error which is caused due to the secretion so basically it gives a correct value of the GFR. Now for renal plasma flow we want a substance as I already told that which should be secreted also so try to understand this that basically this much amount of renal plasma is entering say suppose X amount of the renal plasma is entering. Now some percentage of it that is approximately 20 percentage of renal plasma flow is getting filtered okay. So if a substance is freely filtered that means 20 percent of the substance will also get filtered in the tibules so that substance will be present here isn't it so if only this much is being cleared then we will have the estimation of GFR not of renal plasma flow. We want that whatever plasma is entering into the renal tibule should be cleared of the substance so that is done by actually active secretion of the substance so the entire plasma in which it is present is getting cleared so hence it will give an estimation of the renal plasma flow. So substance which is used for estimation of renal plasma flow is para-amino-hypureic acid so that is the one which is being secreted but one thing you should remember that again this is a substance which is being injected into the person the concentration of the substance in plasma should be less than 20 milligram per 100 ml if we inject more the concentration will increase but why do we want it like that see whenever there is secretion there are certain transporters involved in the tibules and all transporters have a maximum limit or transport so if the concentration is greater than 20 milligram per 100 ml they will not be able to secrete an entire substance into the tibules okay so that is the reason that the concentration of pH should be less than 20 milligram per 100 ml of plasma okay one more thing here that even though we are considering pH for estimation of the renal plasma flow actually the blood which is entering into the kidneys goes to some places where nephrons are not there like there is perirenal fat then there is a renal capsule whereas pelvis, glises so if where nephrons are not there obviously the substance cannot be secreted into the tibules from there so that substance will remain in the plasma itself so that plasma is actually not getting cleared of the substance isn't it so the amount of plasma clearance which we get from pH is actually known as effective renal plasma flow it is not the actual renal plasma flow it is the effective renal plasma flow and it depends that how much pH has been extracted from the plasma it is known as the extraction ratio for the substance so in this case approximately 90% of the pH is being getting secreted into the tibules so the extraction ratio is 0.9 only 10% is not getting secreted so to determine renal plasma flow we just have to use one formula where we can use effective renal plasma flow divided by the extraction ratio so generally this effective renal plasma flow comes to around 600 ml per minute and the extraction ratio is 0.9 so this gives approximately 650 ml per minute of renal plasma flow now from this value of renal plasma flow we can determine renal blood flow also if we know the hematocrit so this is there's a formula for that renal plasma flow into 1 divided by 1 minus hematocrit how that formula is achieved and all that is not the subject of this video so but basically if we know the renal plasma flow by the clearance of pH then we can determine renal blood flow as well okay thanks for watching the video if you liked it do like the video share the video with others and don't forget to subscribe to the channel Physiology Open thank you