Proximal Convoluted Tubule (PCT): Clinical Effects

00:01 Our discussion earlier was dealing with bicarb. Talked about the physio of it all. Let us give it some clinical correlations like you should be doing in every step of the way. Normally, with this, we are talking about lowering the renal threshold for bicarb. What does that even mean? That means that you're actually not reabsorbing bicarb. Listen to what I just said. We are going to lower our standard terminology, the renal threshold for reclaiming bicarb, which means what? That means the more the bicarb remains within the urine and you are going to get rid of it. So, therefore, your normal bicarb level, which is between 22 to 26, and we are using 24 has now dropped down to 15 where, please? In the plasma, right? Now you tell me, acid-base disturbances from physiology. If you were to drop your bicarb down to 15, what does that mean to you? Acidosis because you don't have as much bicarb. You have lost it. What kind of acidosis? Is this respiratory acidosis or would this be metabolic acidosis? Good. Metabolic acidosis. Are we clear? If metabolic acidosis, let me take one step further, just to make sure we are good here. If you have metabolic acidosis and how you are going to compensate? You are going to try to blow off your carbon dioxide very quickly so therefore within minutes, you are going to start hyperventilating, so that you can blow off that carbon dioxide, aren't you? Continue. So now this results with what? Loss of more of your filtered bicarb than the normal renal threshold. Why might you want to do this? As a method of compensation maybe perhaps you are doing this. Remember that high altitude patient that we talked about acutely. In acute high altitude sickness, in which that patient is hyperventilating, blowing off the carbon dioxide resulting in what, please? A primary respiratory alkalosis. How can you confirm that? The pH will be above 7.45. And what is the kidney doing within days? Here we go. You are going to decrease the renal threshold for reclaiming bicarb. So what happens to the pH in the urine? Stop. Listen. Urine pH is going to increase above 5.5. Why? Understand the concept first because there's more bicarb that is left within the urine. What happens to the activity of carbonic anhydrase in the PCT? Upregulated or downregulated? Downregulated because you are trying to get rid of the bicarb. Do you see these questions that are all related. Urine loss of bicarb, what happens? Occurs until serum bicarb matches the renal threshold. For example, let us say that you do give your patient who has high altitude sickness acutely, acetazolamide.You inhibit that carbonic anhydrase so therefore what happens to this threshold that are reclaiming? The lowering the renal threshold for reclaiming bicarb, your pH within the urine is going to increase.

03:10 The bicarb combines with sodium and you get rid of your sodium bicarb, acting in the PCT where we are right now and so, therefore, you are going to, in this particular case, what is my full diagnosis if there was a pH of 7.6? Stop there.

03:27 7, alkalosis. You find that your carbon dioxide is 25. Tell me diagnosis so forth, primary respiratory alkalosis, correct? What is normal carbon dioxide? 40. As you blow off more carbon dioxide, what did it drop down to? 25. What is the only method of compensation? Is it minutes or is it days? Well, the only method of compensation would be kidneys, thus days. Correc,t good.

03:56 So, therefore, you are trying to get rid of that bicarb. For diagnosis, you do have at this point, days later, primary respiratory alkalosis with compensatory metabolic acidosis. Clinical correlations with everything we talked about.

04:16 Going to next point. Now you have raising renal threshold for reclaiming bicarb, the opposite and here we will give it a clinical tag. What is it before one? You are lowering the renal threshold for reclaiming bicarb. But here, you are going to increase your threshold so that you reabsorb more bicarb. Why might you want to do this? Let's do vomiting. If you are doing vomiting, what may then happen? Well if you're vomiting, what you are doing is you are then getting rid of your acid. And so, therefore, if you are going to get rid of your acid, then what might you be resulting in? Watch this. Increasing threshold means that the proportion more of the filtered bicarb is actually being reclaimed. Increase in the reclamation of bicarb is most important contributing factor to increase the serum bicarb and so, therefore, you are resulting in metabolic alkalosis. So this is rather interesting, why? Up until this point, you might have learned in medical school, or maybe you know sometimes you are in a habit of keeping things so simple that you actually missed the details. Or maybe you spent so much time focusing upon the mnemonics, that you really have forgotten the pathophys, or maybe even really not even understood in the first place.

05:31 Listen. You know that vomiting is metabolic alkalosis, isn't it? You might have learned this as being what? Vomiting. Now, what do you see on the floor? Acid. You think, and that may be a good way of remembering if you get rid of your acid, your body is in a state of metabolic alkalosis. That is the wrong method. I mean that might give you the diagnosis quickly, but what if there is a physiology question and that they really wanted you to know what is going on? I'll walk you through this. So when you vomit, you are getting rid of your volume. Take a look at the volume depletion as being our other example. Okay. So now volume depletion, in this case we are using vomiting. Okay. I want you to think of the Darrow Yannet box.

06:16 You know what am I referring to? Darrow Yannet box. If you don't, that is okay. Because what it does, the Darrow Yannet box, is divide your total body water into ECF and ICF. Good. You told me earlier that the ECF was 1/3 of your TBW and your ICF was 2/3. Correct. Now, what are you paying attention to? First and foremost, it will be your plasma, or in other words effective circulating volume, right.

06:46 Earlier we talked about effective arterial blood volume, effective circulatory volume, all the same thing referring to the plasma. Isn't that the most important component to monitor at all times? How can you confirm that, Dr. Raj? Carotid sinus with the baroreceptors and down the afferent arteriole, we talked about juxtaglomerular appartus. So far so good.

07:05 Okay, so say that you are vomiting, what are you doing? You're volume depleting, and so, therefore, the mark of ECF meaning the plasma has actually decreased. Are we good there? What is that called? Contraction. So if you have enough vomiting taking place, enough contraction of your ECF, who is going to kick in? You are going to have your aldosterone, aren't you? You are going to have some of that aldosterone kicking in? Sure you will.

07:32 And if you have some of that aldosterone kicking in, then at some point, what is is actually trying to do? It is trying to get a point where, well it is trying to retain everything that it wants and so the aldosterone is going to try to kick out the hydrogen and so, therefore, that is going to contribute the metabolic alkalosis. In addition, there is going to be an increase in reclaimation of your renal threshold of bicarb. So there is going to be increased reabsorption of bicarb as well, in the hopes of trying to restore some of the volume depletion. All these, ladies and gentleman, is then going to give you the consequence or sequealae of what vomiting does to your body? It is called metabolic alkalosis. From henceforth, sure. The quick and easy you want to think of vomiting as getting rid of acid in a state of metabolic alkalosis. That is a combination of aldosterone getting rid of your hydrogen and also increase reclaimation, increasing the threshold for reclaiming your bicarb, which also contributes to what is known as metabolic alkalosis or contraction alkalosis. What does contraction mean? Volume depletion, contraction of your ECF, specifically plasma. We will talk more about the Darrow Yannet as we move forward, but at this point I am just introducing how important it is for you to have that foundation of ECF and ICF and which we're specifically focusing upon in the ECF and that would be the plasma clinically, and from there you can juggle things around. Let us move on.

09:02 So now we have completed our entire discussion of bicarb, beginning with normal phys and understanding as to how you want to apply that in different clinical situations.