Proximal Convoluted Tubule (PCT): Proximal Convoluted Tubular Mechanics

00:01 Now, this table we are going to spend time here. And by the time we are done, you will get a firm understanding as to what is happening with this entire graph and so therefore any questions that are posed at you, you will sit back, relax, take a deep breath and you will approach it and you will conquer this. Let us take a look at the table. The X axis represents only, pay attention only represents the proximal convoluted tubule only. It is not the distal convoluted tubule and it is sure as heck isn't your DCT, only the PCT. That is the entire length here. One hundred percent on the X-axis represents the percentage of what segment of the nephron? PCT. Stop. What is on the Y axis? This is going to be a ratio. You will have ratios now, I hope so because ratios mean what to you? Concepts. Your goal in medicine is to strive for concepts. The more concepts you put into your head, the more that you are able to truly understand in medicine, and no matter what kind of question is thrown at you. You will think about it, but then immediately go to your foundation and you eventually come up with the right answer. At least you will be in the right vicinity right. At least you are not barking up the wrong tree. So the concept of ratio on the Y-axis is the following. Dissect the following. Tubular fluid, what does that mean to you? Urine.

01:34 Plasma is the denominator. Where are you? Blood. Okay. May I ask you something? If your numerator increases, what happens to your ratio? Increases. Okay. I can't help if you got that wrong just now. So if your numerator increases, the ratio increases. Now if you are going to increase your tubular fluid, then what have you done? Is that secretion or reabsorption? Pay attention. Get this right. Secretion, more important. Isn't that secretion? Yes. Well if you increase the denominator, what happens to your ratio? It decreases. What does it mean medically, to increase the plasma level of a substance? That is reabsorption. How can you prove this, Dr. Raj? With this graph, I want you to pay attention to 1.0. You see it? 1.0 is the middle ground. So now if you go below 1, which means the ratio is decreasing, what component or parameter of this ratio are you increasing? The plasma. What does that mean to you? Reabsorption. How can I prove this to you? Take a look at the substances on this graph specifically glucose, find it, amino acids, bicarb. Always pay attention to those three. Those three, as you travel through the PCT on the X axis, what are its features? Reabsorption, reabsorption, reabsorption. Remember once again are you supposed to normally find glucose in your urine? No. Why? Almost one hundred percent. If not one hundred percent, gets reabsorbed. What does reabsorption mean to you? Increase my plasma because it is being reabsorbed. There you have it. So by the time you get to the end of the PCT, the X axis, look how much glucose you have, please? Zipped. Your tubular fluid to plasma ratio is decreased like crazy, for glucose. So anything below 1, you are increasing the concentration of that substance into my plasma, hence reabsorption. Now, does that mean that anything at 1.0 means not reabsorption? Listen. I want you to take a look at sodium. That sodium right there is at dash line and it is right around 1.0. So what does 1.0 mean? It means isotonic. It means that you are exactly where the osmolarity should be with the tubular fluid and plasma and it is at the equal ratio of 1.0. Do you see where sodium is? Sodium is almost exactly at 1.0 from the beginning of your PCT onto the end of the PCT and stop there for one second. If you were to tell me based on this, that sodium is not being reabsorbed in the proximal convoluted tubule, does that make any physiologic sense to you? No. Because you know that sodium, in the PCT, 2/3 of it is reabsorbed where? Sixty-six percent of your sodium is reabsorbed in the PCT. So what is this close to this flat line at 1.0 mean to you? It means that you are reabsorbing sodium in the PCT. Do you remember in the previous discussion just now, that I told you that in the PCT, the reabsorption is in what form? Isotonic. What does that mean to you? A plasma osmolarity of proximal 300, that means that not only are you reabsorbing sodium, but then also water in an isotonic fashion from the beginning of the PCT until the end, and thus you will find sodium to be almost exactly at 1.0. You need to interpret sodium as such.

05:30 Now things that are important for us. I want you to move up to the green lines here. The green lines indicate creatinine and inulin. I want you to focus on inulin first. On inulin, now you tell me, close your eyes and tell me about the characteristics of inulin? Filtered, yes or no? Yes. Inulin, PCT reabsorbed, yes or no? No. Inulin, PCT secreted, yes or no? No.

06:04 No modification of inulin in your PCT. What gets filtered, gets excreted, correct? So therefore, filtered load equals excretion rate. In other words, clearance equals GFR. You understand that from physio, we are good to go. Now we can move on with our discussion of inulin, we're not done it because now you are thinking to yourself "Dr. Raj, I see that inulin. I understand what you are saying from before. I get all about inulin, but I am not quite sure of why by the time I start from the beginning of my PCT with inulin, and I get to the end of the PCT and I will find an inulin is 3.0." This is why. So you know there is no modification of inulin. It remains firmly steadfast in your PCT. There it is. It is never going to move. No modification of PCT. Inulin remains, you think about water in the PCT. Two-thirds of your water is reabsorbed from the PCT. So what happens to the concentration relatively to inulin? If all that you're doing is reabsorbing water, what is left back in the PCT? The solute, which is inulin. If you absorbed your two-thirds of your water, how much do you increase your inulin relatively? Three times, hence by the time you get to the end of the PCT, you have increased your inulin to a level of 3.0. Once you understand that math, we can move on, but you want that to be digested first before we move on. What does this graph represent? Inside the PCT, the more that you reabsorb your water, the more that you have inulin left in your PCT, moved up to 3.0. So tell me about inulin. That is the perfect measure of GFR on this graph, isn't it? Clearance equals GFR. Okay. Let us move on to creatinine, how important is that? You know that it is constantly being broken down by muscle. It is being filtered, correct? Yes. Is it being reabsorbed? Not at all. Is it secreted? Yes.

08:16 How much? Slightly. So therefore if you find that your tubular fluid to plasma ratio in which you will find your line to be counterclockwise what that means is to the left of inulin, then you know secretion has taken place and you know that already about creatinine and you should find a little bit more of your substance inside my urine compared to that what you find at the beginning of the PCT because it gets slightly secreted. Now, what is the substance that you know that is at low levels purely secreted from the PCT? Welcome to PAH, para-aminohippuric acid hippurate and you know that pH you tell me is going to measure what parameter? Renal plasma flows at low levels. We have discussed that like crazy. You understand at least what I have told you earlier in terms of the graph of physio, then in pathology, the different things that are going to go on would make perfect sense and they can’t shake you. At least lay down this foundation for me before moving on.

09:25 Now the only thing that I wish to bring to your attention is a little bit more detail here because these are the type of questions that you will get. Take a look at chloride. At first, it looks like it is increasing, but no. Chloride here, well once again, at first water is being reabsorbed. So relatively what is happening to chloride concentration? It is increasing. Then it hits the flat line. What does that flat line mean to you? It is still being reabsorbed, but how? Isotonically. Exactly what we are saying. Chloride reabsorption is a little bit slower thus, you find initial increase because water is being reabsorbed faster or should I say chloride is being reabsorbed slower, then isotonic.

10:13 What about sodium reabsorption? We already said that it was isotonic in nature. So it nearly matches that 1.0. Now, overall things we've talked about a few times, and actually multiple times here, we have renal plasma flow 600. Here it comes to the afferent arteriole.

10:33 We are going to go through this quickly. We have done this plenty.

10:37 600 mL/min of renal plasma flow coming through the afferent arteriole. Of that, what is filtration fraction? You tell me. Twenty percent, that means 120 is being filtered, how much is left over in my efferent arteriole? 480. Next, what are you going to do? What kind of substance might you want to use so that you can measure all of your renal plasma flow? Low dose para-aminohippurate. Everything gets secreted and you are going to find renal plasma flow. So net effect, what kind of things are we looking for? We already talked about reabsorption and we talked about secretion? I need to put in something else. Ready? What is it that allows for filtration to take place? That is my question. What is it allows filtration to take place? What is that? Up in the glomerulus. It is hydrostatic pressure.

11:28 What is hydrostatic? Pushing. What letter do you use medically to designate hydrostatic pressure? PPP. Use it in your advantage because that is your pushing pressure.

11:41 Hydrostatic. And it is quite high when you are traveling through the afferent arteriole and filtration will take place. In the meantime, what are the strong force do you have in your plasma? I believe it is called oncotic pressure and actual protein should albumin ever pass through your endothelial cells? Never. It should never pass through the glomerulus. So therefore as you go from the afferent to the efferent arteriole, what then remains behind in your plasma? Your albumin. What then happens to oncotic pressure? It increases. Oncotic pressure physiologically should increase as you go from the afferent to efferent arteriole. By the time you get down to the peritubular capillary, look where you are now. By the time you get down the peritubular capillary, your oncotic pressure has increased. That makes perfect sense, why? Tell me about water. 2/3 of your water is reabsorbed. So, therefore, aren’t you pulling the water out? Who is going to contribute to that? The oncotic pressure. Who is that? Albumin. The albumin that never should have physiologically normally filtered through.