Diabetes Insipidus (DI): Management

00:01 Management of nephrogenic diabetes insipidus. Before we move on, think about your patient.

00:06 The receptors aren’t working properly. Therefore how much urine polyurine. What are you producing diluted urine? Tell me about clearance of water? It is increased. Increased free water.

00:17 So far so good. In the meantime, when you are losing all the fluid, tell me about your plasma. Your plasma osmolarity is increased. Now if you have a child that has nephrogenic diabetes insipidus in addition there is going to be further a loss of fluid. Welcome to vomiting, diarrhea, fever there might be sweating taking place. What is your first step of management? IV fluids. You have to granted the fluid might be leaving excessively from the urine, but please understand you still must give it because if you don't have the fluids, then what happens to your blood pressure? My goodness. It drops like crazy. That is your first step of management.

00:58 Next D5W. What does it mean? It is basically pure water. Now you have given it but the only problem is the fact that you are looking for and may then bring about dilutional hyponatremia.

01:11 What is important by D5W? It is the fact that you have to have that dextrose where if it gets rapidly metabolized, it slows down or retards the entry of water into the cell.

01:22 What are you preventing? Rapid swelling and lysis of your cell. Now, why would you even think about giving D5W? What kind of fluid is D5W? Hypotonic, isn't it? It is hypotonic and tell me about your patient with nephrogenic diabetes insipidus. Plasma osmolarity ridiculously high. So, therefore, what might you want to give to then decrease the plasma osmolarity? How about some hypotonic fluid? You see as to how our discussion earlier of IV fluids is absolutely relevant to what is happening here. Take a look at 0.22. 0.22 represents extreme hypotonic. What is normal saline? 0.9. What is half normal saline? 0.45. Here is 0.22. That is quite hypotonic. Next what else might you want to do? Decreased dietary solute preventing osmotic diueresis. Everything that you turn to do ladies and gentleman after your ABCs what ABC mean to you. Whenever you have a patient what are some of the first questions that you are asking so? It is the airway block. What about the breathing or what about the circulation? So if the circulation is affected here in nephrogenic diabetes insipidus, it is IV fluids. Next well why not decrease some of the solutes? Maybe some of that "salt" your sodium so that you prevent further osmotic diuresis. Diuretics. This is interesting.

02:52 Please pay attention here. Okay. Let us go way back to look at the nephron and we had a distal convoluted tubule. Think about that. Are you there? Distal convoluted tubule. Good.

03:05 What kind of symporter do you have? It is called sodium chloride symporter. It is the diluting segment and what receptor is it very sensitive to or what hormone is the receptor based sensitive to? PTH. What does that mean? Calcium reabsorption. What kind of diuretic works in that area? Thiazide. Now as counterintuitive as it may see to give a diuretic, do not give your patient with nephrogenic diabetes insipidus or loop diuretic, you get kicked out of the hospital. Oh! my goodness. But it is shown that thiazide now really the mechanism and the theory behind it is quite complicated. So let us not go there. You go there on your own time and our time let us make sure that you are clear. A diuretic that you would only use in the setting of the nephrogenic diabetes insipidus will be thiazides. So, two unique features actually three unique features of thiazides that you must know. #1 the African population, elderly that have hypertension. Your drug choice or antihypertension is thiazide.

04:17 Point #1 that makes perfect sense. #2 if you have a patient that has too much calcium where, in the urine, then thiazides may be used to remove the calcium from the urine. Isn't that a unique feature? Yes, it is. #3. Thiazides can be set or can be administered in the setting of nephrogenic diabetes insipidus. Fascinating. What does it do? Weight loss of 1.5 kg can reduce the urinary output by 50 percent and that has been shown to occur by giving thiazides.

04:52 Look at this. You are reducing the urine output by greater than 50 percent. That seems pretty effective to me that the mechanism let us know at this point research has given us that outcome. Next, the effect mediated by hypovoilemia-induced increase in proximal sodium and water reabsorption, thereby diminishing water delivery to the ADH-sensitive site is the most common theory to be tested and so therefore by doing this then maybe just perhaps you are resulting in reduced urinary output by giving it diuretic known as thiazides. Now finally the problem is this. Amiloride in patients with reversible lithium-induced nephrotoxicity. Isn't this interesting? What does this mean? Remember that lithium and who is your patient? Adult may be and why would the adult be taking lithium for long periods of time. Maybe they are crazy and then maybe they are depressed. Crazy, depressed. Bipolarism right. With bipolarism, taking lithium over long period of time, the lithium then works in ENAC. We had that discussion interesting. What about amiloride? Works in the ENAC. So amiloride in a patient that has had lithium induced nephrogenic diabetes insipidus and you get to the point where it is irreversible.

06:17 Hopefully, amiloride is your drug of choice. Management of nephrogenic diabetes insipidus really ladies and gentleman this is out of the press. You are probably hearing all of this for the first time. You want to confirm this sure. Walk into a clinic and kick butt and be hoisted on the shoulders of your peers and you will see as to how effective you are as being a medical student or resident and so forth. Let us continue.

06:43 Now, ultimately management of nephrogenic diabetes insipidus. Now what we are going to walk through here is the following of very important table. Examples, we will talk about the differentials in the first column. We will talk about serum ADH, plasma osmolarity, urine osmolarity and this is great here because we can actually compare both of the osmolarity compartments adjacent to one another by urine flow rate and then free water clearance. Let us begin. Let us say that you conducted water deprivation test. Close your eyes. Water deprivation, what happens to plasma osmolarity? Increased. You see that. Next water deprivation well you have now plasma osmolarity. You are inducing, for the most part, none of the water in your plasma. It is increased. So what is the body trying to do? The body releases ADH. Take a look at the second column. That ADH comes in what is going to work? Collecting duct and you are going to create what kind of urine? Good. Hyperosmotic urine. What do you think happens to your flow rate when ADH is working? It is low. Stop. Tell me about free water clearance. What does free water mean to you? No obligation to any electrolytes. Okay. So now you have increased ADH in the setting of water deprivation. Let us say a better word for this is reabsorption of water from the collecting duct. What is your clearance of free water? Negative. What is it meant when you have clearance of water being zero? It is not solute-free. What does it mean if you have clearance of free water being positive? That means that you are getting rid of too much water in SIADH or in the setting of ADH obviously your clearance would be negative. That must be understood. Now that lays down the foundation. Now we can move quicker through the differentials. SIADH what does that mean? Too much. Tell me. Plasma osmolarity, but here it would be decreased because you are moving too much of your ADH. Do you understand that? I want you to compare this plasma osmolarity with SIADH and water deprivation because it is important that you walk through chronological and logical steps. If you are water deprived, where do you go first? The plasma. If it is SIADH, what do you go first? ADH. Why? If it is water deprivation, plasma osmolarity increases thus resulting in increased ADH. If it is SIADH, what is it? Yeah ADH is increased in excess. Then you can go through the rest with hyperosmotic urine sure. Low yes negative.

09:36 The rest are the same. But if you don't spend time understanding those two differentials and why ADH is increased and why the plasma osmolarity is opposite to one another, then you missed the entire point and you just memorize. There is no way to memorize this table and question gets questions right. You cannot. You understand this table, then you go into clinic and then you go into doing exams, guaranteed to get everything right. First water drinking.

10:01 With water drinking, where do you want to go first? Good. Plasma osmolarity. So when you drink water, your plasma osmolarity would be low especially excessively. If your plasma osmolarity is low, tell me about your osmoreceptors. They are not going to stimulate release of ADH. Your ADH is now going to be suppressed. If that is now suppressed, then tell me about your urine osmolarity. It is going to be hypoosmotic urine. So therefore when you have more dilute urine that you are producing because the lack of ADH, then tell me about your clearance of free water. It would be positive and your flow rate will be increased. Once you get that done, you will notice the other two. We will talk about here with diabetes insipidus.

10:47 Your focus here ladies and gentleman should be on nephrogenic, but now jut to be complete I have also listed central. With central diabetes insipidus, where is my problem? Good. The ADH was never released. If the ADH was never released centrally, then what happens to your urine osmolarity? It is going to be a really low hypoosmotic and then you have positive clearance. Next what about nephrogenic? We just talked about this in great detail so they should be perfectly clear your kidneys and the receptors are known as V2 receptors.

11:24 May I ask you what that mutatio was one more time? It was arginine vasopressin receptor2 gene in which receptors are not responding to ADH and so therefore what kind of urine are going to produce? You are going to produce really really hypoosmotic urine.

11:44 Good. Stop there for one second. I told you this earlier. This was a concept. If the receptor in a pathologic condition are not functioning, what is always the state of the hormone that should be working on it. High, high, high. Good. Take a look to ADH, ridiculously high.

12:03 But why is it that your urine is too hyposomotic? Because the receptors aren't functioning.

12:08 They are still clearing lots of free water and urine flow rate is going to be high. You spend a little bit of time on this table. Understand the pathophysiology for each one of these parameters. Seriously. Clinically speaking, there is no way that you didn't get a single question wrong.