Distal Convoluted Tubule (DCT): Antenatal Bartter Syndrome

00:00 Continue.

00:01 A couple of other things. There are different types of Bartter and I wish I can tell you that, that's all that you needed to know. With Bartter, first and foremost with no foundation, problem with thick ascending limb, sodium- potassium-2 chloride. There is a problem with concentrating ability and there is a problem with hypercalciuria. Much more so.

00:23 So far so good. We have what is known as well I, IV and IVB. There are different types okay.

00:31 So antenatal Bartter meaning right around birth, antenatal, is a hyperprostaglandin E2 syndrome. All that you need to know is this. Keep this in mind. There are many types of Bartter syndromes that are associated with hyperprostaglandinemia, Why is that important? Because at some point remember our entire course here in pathology is you being a doctor.

00:58 You being able to identify your patient based on knowing the normal, abnormal, at least be able to know a little bit of management okay. Because otherwise you miss questions and you don't want that. So you will have many Bartter syndromes that are associated with, what is known as hyperprostaglandenemia. Okay. Now if you want to know I, IV and IVB, that is fine. It might be a litte bit too much detailed, but keep in mind hyperprostaglandin. Now what is important is you want to know these these genes. It is called ClC, means to say they are chloride cotransporter channel highly expressed in the inner ear to maintain high potassium concentration in the endolymph. Why is that important? Because in these conditions IV and IVB types of Bartter, keep this in mind because these are distinguishing features that I can't even tell you how important is this clinically. Boards and wards they just love asking questions like this and if you answer this, you see as to how you will be a shining star. So here IV and IVB type of what is known as Bartter syndrome apart from having hyperprostaglandinemia, these chloride channels ClC-K is also necessary for proper endolymph in the ear to have a hearing and vibration and if you don't have these channels working properly not only are you going to have issues in the kidney, but then you have issues in the ear. Stop there.

02:28 This might be your very first time that you have heard of this. You have heard it here and you will be asked and when you are seeing this and you are hearing this, you are getting question and you are so confident about getting this right. You will feel good. Point being is there is another issue in cardiology in which we talked about how you might have long QT syndrome. Remember this. Long QT syndrome and deafness and that was called Lange-Nielsen and Lange-Nielsen is a congenital QT syndrome associated with deafness. Romano-Ward was congenital long QT syndrome without or no deafness. So these here is to how these distinguishing features or things are so loved to be asked. So here we have Bartter syndrome and you have type IV, IVB associated with deafness. You want to know ClC-Ka. Move on. Epidemiology clinically your patient here antenatal, childhood. Now overall though understand the Gitelman syndrome is much more common than Bartter, but at least know these distinguishing features of Bartter before moving on to Gitelman. Lets move on.

03:44 In Type–I, antenatal Bartter syndrome things that you want to keep in mind. First of the bat, we talked about sodium-potassium-2 chloride, two gene. stop there.

03:54 Next, pay attention to what is happening here. Overall, you will lose your potassium, hypokalemia.

04:00 You have hypomagnesiumia and remember as to what your level aldosterone is. It is increased. Right? In the hopes of restoring the blood pressure. So you get rid of your hydrogen, hence result in metabolic alkalosis. That is the only one that might be little tricky, but there is enough information here. You should not miss a single question on Bartter. Let us now move on. Other aspects; growth and mental retardation, volume depletion hence we talked about the issues with aldosterone. Also, the most important point here is look at increased prostaglandin and so, therefore, management often times in Bartter is try to antagonise the prostaglandin.

04:45 So what might you be thinking about? How about COX inhibitors? That is interesting.

04:50 Ever heard of management of Bartter with NSAIDs? Now you have, and you should know it. Muscle weakness due to hypokalemia. Now integration, I can’t just walk past this knowing that you will be asked other questions from physiology. You lose your potassium. We have increased aldosterone in company and when you lose your potassium, resting membrane potential becomes what? More negative. As your resting membrane potential becomes more negative, where is my threshold? It is further away. It is more difficult to reach threshold thus in terms of triggering an action potential, not as ready. So, therefore, you are looking at muscle weakness and heart issues. Do not forget that. In general, hypokalema you should know always causes muscle weakness for reasons we just talked about. The secondary hyperaldosteronism because of warm depletion, polyuria, polydypsia. Remember you are going to lose quite a bit of calcium. Normal or hypercalciuria, highlight that. Leading to possible secondary hyperparathyroidism.

05:55 Stop there. More integration. What do you mean? If you have hypocalciuria, where is my calcium? In my urine. Good. More that you are losing calcium in your urine, you might actually have decreased calcium in the blood. Pay attention to suffix here uria. If you have decreased calcium in the blood, what are you going to trigger? Secondary hyperparathyroidism.

06:21 Everything that you do here you want to make sure you are alert, you have full of energy and you are with me and give yourself these tags over, over, over and over again and really, they can't fool you. What is your management? Lets take care of the prostaglandin. Indomethacin. What is that? A cox inhibitor. NSAIDs. Why? Many types associated with hyperprostaglandenemia. Next, you are going to lose a lot of potassium.

06:49 Why not use the drugs to try to spare them. For example, spirinolactone, which is what? An aldosterone antagonist. Good and then ACE inhibitors. ACE inhibitors might be used here so that you can prevent some of these issues with blood pressure and the fact that you have problems with prostaglandins and so forth. But main stay therapy indomethacin and potassium-sparing diuretics. Lets continue the discussion.

07:20 After Bartter and thick ascending limb and go further distally. So now we're in the distal convoluted tubule. Quickly once again to recap. Here is my sodium chloride channel. You see where we are? Good. You see that receptor on the basolateral membrane? That receptor is called the parathyroid hormone receptor. Last time we talked about that was well hypoparathyroidism primary and what was the other one where I talked to you about, where i have referred to it knuckle, knuckle, dimple, dimple. Oh, that was your pseudohypoparathyroidism. Mean to say the receptor is not responding to parathyroid hormone. Just to make sure we are clear that pseudohypoparathyroidism presentation, you have a short patient. Short stature patient and the dimple dimple refers to your fourth and fifth, your pinky and ring finger, the metacarpophalangeal joints and they are not present. I am going to reinforce this. Not to worry. Just want you to see as to where the problem is. Now getting back on point we have sodium and chloride. These are thiazide sensitive. In addition the PTH works here to do what? Reabsorb calcium, has no affect here in terms of inhibition of phosphate, that was in the PCT remember and PTh works in the PCT to stimulate the enzyme 1 alpha-hydroxylase. Here it primarily works. Take a look at the bottom box there on the basolateral membrane so they can reabsorb calcium. Give me a drug that might also a diuretic obviously that is going to reabsorb calcium. Welcome to thiazides. Now the distal convoluted tubule actively reabsorb sodium and chloride. It is known as the diluting segment because it is water impermeable makes the urine hypotonic further. Site of PTH action highlight this in your mind you know that it is calcium coming in. Calcium reabsorption.

09:17 So therefore, in a condition such as primary hyperparathyroidism, there is too much activity on the receptor by PTH thus there is going to be increased reabsorption of calcium. Stop there for a second and you give me a paraneoplastic issue. A paraneoplastic issue is going to increase production of not exactly PTH, but PTH like. Good. Squamous cell cancer of the lung. Give me another one. Renal cell cancer of the kidney, obviously. So RCC, renal cell cancer, squamous cell cancer of the lung. These are two cancers two different organs producing not exactly PTH. Hence we called this PTHrP, the operative word RP. That is related peptide to PTH. Does work on the receptor? Yes it does. So therefore will it reabsorb calcium excessively? Yes it will. Is PTHrP the same thing as PTH? No it is related but it is not the same thing. Are we clear? Why? How are you going to intrepret the labs here? You find excessive calcium, hypercalcemia with PTHrP and that excess calcium tells my parathyroids to be what? Shut down. Interesting, isn't it? You have increased PTHrP, increased calcium, but a decrease in actual PTH. Do not forget that. We will reinforce it. You can see that we are adding more and more pathology through every single slide in every single concept. Build, build.