Cram The Pance - S1E6 SIADH vs. Diabetes Insipidus

Episode Date: January 14, 2021

Today we go over SIADH and Diabetes Insipidus!►Paypal Donation Link: https://bit.ly/3dxmTql (Thank you!)--- Support this podcast: https://anchor.fm/scott--shapiro/supportBecome a supporter of this podcast: https://www.spreaker.com/podcast/cram-the-pance--5520744/support.

All right. So today we're going to be doing SIA-H and diabetes insipidus. And before we actually dive into the diseases, I think we should do a quick review of what ADHD is, because this is very important to both of these diseases. And if you don't understand what it is, you're not going to really understand what's going on in the body. And this will help you understand it a little bit better. So I'm going to be brief, break it down into a very simple, simple way to understand it. So ADHD is known as antidiarrotic hormone, also known as arginine vasopressin. it's produced by the hypothalamus and stored in the posterior pituitary when it's released when needed by the body. So what is ADHD and why is it produced?

So the most important role, and this is just really simplifying it, but the most important role, the main role of it, is to control the volume of fluid in the body. So the pituitary has osmoreceptors that can sense the volume status of the body, the plasma osmolarity. And essentially what the pituitary will, recognize is when the body is, say, dehydrated, it can sense this change in plasma's malarity. It knows the body's dehydrated, so the pituitary starts releasing ADHD. What does ADHD do?

ADH tells the kidneys, retain all of the fluid you can. We're dehydrated. We can't afford to lose any. So the kidneys will pull back all of this excess fluid and it won't release any into the urine. Where the opposite is true, the patient is volume overloaded edema, whatever it is. It's going to slow down the production of ADHD, which will allow a lot. of this fluid to be released through the urine. So that's a breakdown, a basic understanding of what ADHD is so we can kind of go into the diseases to understand them better. So let's start with

SIA-DH. That stands for syndrome of inappropriate antidioretic hormone. So it's all in the name. It's an inappropriate release of ADHD. In this case, ADHD is being released in excess more than what the body needs. It's not responding to volume status. It's just cranking out ADHD all the time. So what happens when you crank out ADHD is the body is going to retain all. of the free fluid. Nothing's going out in the urine. So the urine's going to be concentrated. And these patients can become hyponatremic. They can become really sick because of this. So what are some of the causes of S-I-A-D-H? Well, one of the most common causes is going to be something going on in the head because this is where the pituitary is that's releasing this hormone.

So one of the most common causes is going to be a subarachnoid hemorrhage. That's a really important one. Don't forget that. Some other causes can be a trauma to the head, a CVA, which are all important as well. Another really big one that you may see on your exams, your boards is small cell lung cancer. So why is small cell lung cancer going to change the ADHD production of the body? Well, it turns out the malignant cells in small cell lung cancer can actually provide an ectopic source of ADHD. So these malignant cells are actually pumping out ADHD. Some other causes that's really important as well is anticonvulsants, carbamazapine in particular, can cause SIA-A-DH.

And then some other meds, too, not as important, but TCA's, SSRIs, the antidepressants, hydrochlorothyside as well. If you're going to remember three, though, just remember the subarachnoid hemorrhage, small cell lung cancer, and anticonvulsants. Those are the big ones. Those are the real important ones that you should remember for your boards and remember for real life because these are some of the more common causes of this. How is the patient going to present?

Depends on the severity of the illness, but they may have altered mental status. they may even be seizing, they may be in a coma, all due to severe levels, severe cases of hyponatremia and cerebral edema. As far as the diagnosis, these patients are going to have a normal volemic, hypotonic, hyponic, hyponatremic state. So let's break down each one of those because they sound pretty similar and let's kind of understand what they mean. So normal volemic means that the patient in presentation is going to present normal. They're not going to appear to be volume overloaded. They're not going to have all this edema, swelling in the legs. They're going to appear normal volimic.

So their appearance is going to be normal. They're going to be hypotonic. So this is actually going to be related to the solute concentration. It's going to be a low solute concentration because remember all of this fluid is saved up in the body. So comparison to the actual solutes, they're fluid overloaded. And then they're going to have hyponatremia, again, because this is going to have all this excess water relative to the sodium amount. So hyponatremic as well. Some other labs that you're going to see, obviously you're going to have increased ADHD levels. And then they're going to have a decrease in serum

osmolarity. And why is that? Well, serum osmolarity is related to the concentration level of the actual serum. So if you have an increased osmularity, this is going to mean that the serum is very concentrated because remember when we're looking at osmolarity, we're looking at the relationship between the solutes and the actual solution and the amount of fluid. So increased osmolarity is going to mean that there is increased solutes compared to the amount of fluid. And in a patient with SIADH, they're actually going to have all of these increased fluids saturating the serum, which is going to water down the serum. And there's going to be a decreased solutes compared to the amount of fluid. So they're going to have a decreased serum osmularity, which is going to be a dilute

serum. An increased serum osmolarity is going to be a concentrated because remember that's more solutes compared to the water. So really quick again, because it can get confusing, especially in a podcast. If you have a decreased serum osmularity, this means it's going to be a dilute serum. It's going to be fluid overloaded. Solutes compared to fluid. There's going to be a lot more fluid than there is solutes. And then an increased osmularity means that it's very concentrated. Remember we're thinking about the actual, the amount of solutes in the actual serum. So an increased osmalarity means that it's concentrated. There's more solutes compared to the fluid.

A decreased osmolarity means that it's dilute, less solute compared to the amount of fluid. So hopefully I didn't lose you there. I'm trying my best to help you visualize that. Then some of the things that you're going to see, too, is you're going to have a decreased serum osmularity because fluid is staying in the body. But the opposite will be true of the urine. The urine is actually going to have an increased osmularity. And this is because the urine has very little fluid in it. Again, remember, we're looking at solute.

here. So increased urine osmularity, meaning it's very concentrated because there's decreased fluid coming out in the urine. So it's very concentrated. Normally you're going to see over anywhere from 20 to 40 mil equivalents in the solution. So remember, the urine is very concentrated, increased urine osmolarity in S-I-ADH and a decreased serum osmolarity. Remember, where is the fluid going? These patients are producing too much ADHD, telling the body, hang on to the fluid, which is going back into the serum. So you're going to have this overloaded serum with fluid and you're going to have a dilute serum. So decreased serum osmilarity, the urine has very little fluid coming out. So you're going to have an increased urine osmularity because there's decreased fluid in very high

concentration of the solutes. As far as treatment, you're going to treat the underlying cause. So, you know, if it's caused from a medication, if it's caused from a cancer, subaractment hemorrhage, whatever it is, you want to treat the underlying cause. And it all. depends on the level of severity. So if you have a mild patient who's, you know, asymptomatic and doing pretty well overall, the first thing that you would do is just restrict their fluid intake, which will help kind of level out the hypoenatremia scene. The patient's a little bit more severe. They're starting to have symptoms. They're not doing as well. You can use something called a vasopressin receptor antagonist, which is actually something that blocks the effect of ADHD.

So it's essentially just blocking the function of ADHD. And one of the names of the medication in this class is something called Tovaptan. And again, this is just going to block the effect of ADHD. If you have a really severe patient, they're symptomatic. They may be in a coma seizing alter mental status. You want to go right ahead and give them IV hypotonic saline to correct the hypotonic state that they're in. And then also you want to give them furozomide. Because remember, furoosomide is a lup diuretic and it excretes all of the excess free water that's in the body.

So that's going to be in a severe patient that you would jump to those treatment options. Sometimes patients will have these chronic causes of SIA-DH, this recurrent condition. And the medication that we use in these patients is actually a tetracycline derivative. And it's called demi-close-cycline. Demi-closycline. It's a tetracycline derivative. The exact MOA of this medication isn't really clear. But it's thought that it induces a nephrogenic diabetes insipitous by inhibiting ADHD

effects on the kidney. It binds to the vasopressin receptors in the kidney. So probably a little bit too much info there. But if you have a chronic patient, you can use demiclocecline, tetracycline derivative, which will block the ADHD. They used to actually use lithium to treat this. But obviously, we know lithium has a lot of side effects. So once this medication came out, this is the safer alternative. And this is what they use now.

So let's move on to diabetes insipidus. So this is going to be the opposite of SIA-DH. This is going to be a patient who doesn't have enough ADHD. So whether it's a decreased production or the kidneys just not responding to the ADHD, this is going to be the opposite. We don't have enough ADHD or the effect of it isn't significant enough. So these patients are going to be passing a lot of urine. They're going to have polyurea, polydipsia. And just a quick side note, the name diabetes insipidus is a little confusing because clearly this patient's not diabetic.

But the way they came up with his name is when it was diagnosed hundreds of years ago. When they used to diagnose diabetes, they would have these patients that would come in with frequent urine. and they used to actually taste the urine, and the urine would be sweet because of all the sugar that's coming out on these diabetic patients. So what diabetes insipitous means is insipitous is actually, or insipid is the Latin word for tasteless. So they described it as a diabetic patient with tasteless urine. So diabetes insipitous, just an interesting side note to keep you entertained there. So anyways, these patients are going to be two different causes. Either they're not producing enough ADHD, which is going to be known as central.

diabetes insipidus or their kidneys aren't responding to the ADHD that's being produced and that's known as nephrogenic diabetes insipitous. So the kidneys aren't properly concentrating or absorbing water. They're going to have large volumes of watered down dilute urine. So talking about central again. So central for some reason that pituitary is not releasing enough ADHD. It's just not producing ADHD. It may not be producing at all or just may not be producing enough. This is going to be your most common type, central diabetes insipidus is your most common type. Generally, it's idiopathic, but it can be due to some type of pituitary injury, destruction, or some trauma to the head can cause central diabetes insipidus.

Nephrogenic diabetes insipidus is going to be when there's, the ADHD production is fine. The pituitary is releasing it just like it should, but the kidneys aren't responding to it. So the kidneys don't care how much ADHD is being produced. They're just not responding. So what are some of the causes of this? The one that you should definitely know is lithium. And like I said before, it used to actually be a treatment for S-I-A-D-H because it can induce

diabetes insipidus and reduce some of the symptoms of, I'm sorry, of S-I-A-A-D-H used to be a treatment for S-I-A-D-H because it can induce diabetes insipidus. So lithium is a big cause of nephrogenic diabetes insipidus. That's something you need to monitor in patients if you're treating them with lithium. So that's a big one. Amphotericin B is another one that you should know as well. And then some electrolyte abnormalities can cause this as well. So hypokalemia and hypercalemia can also cause nephrogenic diabetes insipitis.

And this is due to these abnormalities, these electrolyte abnormalities can actually cause the kidney to decrease its response to ADHD. So how is this patient going to present? They're going to be peeing and drinking like crazy. So polyureum polydipsia. They may even have altered mental status from hypernatremia. And why are they drinking and peeing so much? Well, they're drinking because all of the fluid that they're pulling into their body isn't being retained.

The kidneys aren't pulling any of the back into the body. So these patients are dehydrated. And they're drinking so much because their body, I'm sorry, and they're peeing so much because the ADHD isn't being released or responded to. So the kidneys have no ability to retain any of this fluid. So they're drinking and peeing like crazy. That's the main thing you should know in the patient presentation. As far as the physical exam, you're going to have a volume depleted patient.

They're going to have dry mucus membranes. They may be hypotensive. And then what about diagnosis? So there's a few things that you're going to see on presentation. So you're going to have an increased serum osmolarity. This is because, again, we're not retaining any fluid into the body. We're not pulling back any fluid. So the osmolarity, this is going to be concentrated.

The serum osmolarity is going to be concentrated in the body. There's going to be a large amount of solutes compared to the amount of fluid. Whereas the urine is going to have a lot of fluid. as the urine is going to have a decreased urine osmolarity because you have this dilute urine. So the solutes compared to the actual fluid, there's going to be tons of fluid in the urine, but not much solute. So you're going to have a decreased urine osmularity. You may also have a decreased specific gravity.

If you remember that specific gravity can actually be used in a urinalysis to check hydration status. And if a patient's well hydrated, it's normally going to be higher. and in this case, obviously, these patients are very dehydrated, so it's going to be decreased the specific gravity. So one of the tests that you can do to diagnose this, the first thing that you would do is something called a fluid deprivation test, and it says exactly what it is. So you're going to deprive this patient of fluids for about eight hours. So in a normal patient, what would happen? If you have a normal patient that you don't give anything to drink for eight hours, I'm sure we've all been dehydrated before.

We didn't drink for a few hours. And if you remember, your urine gets very concentrated. In these patients, though, they're not going to drink for eight hours and their urine is still going to be dilute. Normally under 300 millie osmoles. So you're going to deprive them of fluids for about eight hours and their urine is still going to be dilute. It's not going to be concentrated because the body doesn't have the ability to do this. And a normal patient, of course, the urine should start to become concentrated and become that darker yellow orange. and these patients that does not happen.

So once you make the diagnosis, you need to figure out what is the cause. Is it central or nephrogenic? So the way that you do that is you go ahead and you give these patients ADHD. And that's the synthetic ADHD is known as desmopressin. And when you give these patients ADHD, if you kind of think about it, how do you think a patient that has central nephra diabetes insipatives? How do you think they would respond? They have a pituitary that isn't releasing ADHD.

and you give them ADHD, they should respond positively. They're deficient in ADHD. The kidney's working fine because, again, this is a central cause. So you give them ADHD, and then all of a sudden, kidney starts working. They have this increased serum osmalarity. Everything goes back to normal. The urine starts to be more concentrated and everything's normal. But in a nephrogenic diabetes insipitous patient, you give them ADHD, and it doesn't matter

because the kidneys aren't working well. So it doesn't matter how much ADHD you give them, the kidneys aren't to respond to it, the urine's still going to be dilute. So that's how you figure out which cause it is. You give them ADHD. If they respond to the ADHD, it's going to be central. If they don't respond, it's going to be a nephrogenic cause. So very straightforward, pretty simple. And then how do you treat? Well, if it's central, again, what do you think you're going to give a patient with central diabetes insipitous? You're going to give them ADHD. You're going to give them desmopressin. So that's going to be your first line treatment. And then if it's nephrogenic diabetes insipitous,

you're going to fix the underlying cause. So are they taking them? lithium or do they have electrolyte dysfunction or do they have hypercalcemia hypochalemia fix these abnormalities and you should fix the problem um there's another medication called ameloride and this is something you give a patient who was taking lithium and developed nephrogenic diabetes insipidus um and what ameloride does is it actually prevents entry of lithium into the nephrons by blocking the sodium channel so this can work in a patient who's been taking lithium so you can fix it with that. Another medication you can use as well to help is hydrochlorothiozide. And this is going to create a mild hypovalemia and encourages the kidneys to retain salt and fluid. So that's another treatment option as well. But the main treatment

option for nephrogenic is going to be to fix the underlying cause. That's the main thing. So I hope that helped you guys. And I try to make it as brief as I could and I try to explain things as best I can. I know this is a little bit trickier of a subject. But I hope that helps. rate the podcast let me know if this is helping you and subscribe i'm going to try to be releasing these again about every three to four days and good luck in pa school good luck on your exams and let me know how you guys are doing and how you feel about this podcast