Actions of ADH: Diabetes Insipidus (DI)

00:00 Actions of ADH. Once again I wish to reiterate the emphasis here with ADH is going to be its effect on the kidney and when it comes to pathology. In nephrology, we will be focusing and have been focusing upon nephrogenic diabetes insipidus, which just came up of a very important discussion as to the mechanics of your ADH receptors on your V2 receptors and the fact that it works with GS. Spend a little bit of time with that concept so that you understand at some point in time if they do oppose a question, how do you bypass the receptor while you do everything in your power to then increase production of the cyclic AMP so that you can then insert the aquaporins and continue through the process of reabsorption of water. Now with that said once again we reiterate the V2 receptors are on the kidney and specifically in the collecting duct and as long as your ADH is present. Would you please take a look at the picture here where you will find on your left side the actual medulla and the lumen and as you move distally through the collecting duct, we go from proximally less than 300 all way down to 1200. Wow! what is normal isotonic plasma osmolarity? Approximately 300. Here we have urine osmolarity at 300 moving all way to 1200. Do you think that the effective ADH is present here? Of course, it is and so, therefore, you are going to reabsorb that water and as you move from the lumen and over to your right is your vasa recta. What does that mean to you? Your peritubular capillaries. Reabsorption is taking place and putting that water back into the plasma with the help of ADH. Now that will be your primary focus. Now what I wish to bring to your attention one more time is the fact that ADH also known as arginine vasopressin may then work upon your blood vessel in which as you see here would be responsible for releasing some of its von Willebrand factor. Now what will you also find to be interesting is the most of your factors, your coagulation factors, in fact, are being produced where? You see the liver there on top. On your right a big gray mass that is your liver and that is going to be producing all of your coagulation factors except a few and those few include von Willebrand factor and that you have factor VIII. Where would these be coming from? These would be then coming from your endothelial cells. Now the receptors that you find here are V1 receptors. They are responsible for, do you see this? It is kind of looks like a bottleneck, doesn't it? Mean to say that as we take a look at the diameter of the blood vessel on top, it looks narrowed and there would be the effects of ADH being exerted upon your blood vessel whereas if you take a look at the bottom portion blood vessel, you will find any ADH down here? No, you don't. So, therefore, what is this state of my blood vessel? Not vasoconstricted. Let us continue. So now you are releasing von Willebrand factor. What must factor VIII have in its association? It is optimum functioning of factor VIII. Obviously von Willebrand factor. I am going to bring another pathology appear one more time all about reinforcement. If you have a female and she is bleeding excessively during her menses, then you get labs in which you start reading the following. You will find an increase in PTT and you will find an increase in bleeding time and with that type of history, you are most likely. Well, what is your next step of management? There is something called and we will talk about this called ristocetin assay. Now ristocetin is a very expensive test. That is important for you to know. That is why you don’t readily call or request for a test of ristocetin because it is too expensive. Now as said it may be seen in the idealistic world, oh! you can order whatever you want. Now that is not the case. You have a doctor but hospital is a business. When you have a business, what are you looking for? Cost effectiveness and how to generate revenue. Unfortunately, you are in a situation where you are responsible for that as well. So, therefore, you next step of management to confirm your von Willebrand disease, in fact, is your risocetin. Now what I wish to also brings to attention now this makes sense. Take a look at factor VIII. If you don't have von Willebrand factor, factor VIII isn't working properly. If factor VIII isn't working properly, well you remember from hemodynamics the factor VIII is part of the intrinsic coagulation pathway. The intrinsic coagulation pathway is then tested with PTT. What was the that I gave you in von Willebrand disease that was elevated PTT.

04:53 Is that clear? Why? Because then factor VIII isn't working properly. That is test #1. Okay, but then what is the other test that I mentioned? Bleeding time. I will give you the times later, but actually, I will give it to you now. Why not? Two to seven minutes is bleeding time.

05:10 Well, here you will find your bleeding time to be greater than seven minutes. How does this occur, please? It is a fact that you require von Willebrand factor to then bind to platelets. So if you don't have the von Willebrand factor, guess what? Your bleeding time is going to be elevated. Confirming von Willebrand disease. Let us continue.

05:30 Vasopressin analogs for the management of von Willebrand disease type I. Now understand there are five if not more different types of von Willebrand disease, the one that you want to know for sure in which you are deficient of von Willebrand factor is type I von Willebrand D disease. What is an analog here that you want to use to release the von Willebrand factor? How about some vasopressin? There it is. In addition, what are the conditions might you be thinking about to treat with vasopressin? There is hemophilia A. What is hemophilia A? AB89. What I am saying? In the alphabetic order, A comes first. Chronological order 8 comes first. Factor VIII deficiency is hemophilia A. Vasopressin may release factor VIII. Let us continue. Now the supra-physiologic levels. ADH works on V1, where is that? On your blood vessel, therefore, bringing about vasoconstriction that is which you are seeing here bold in green.