March 21, 2023

Spironolactone is a medication used commonly as an androgen blocker in those undergoing feminizing transition. Today we’re going to discuss the most common side effect of this medication: excessive urination.

So hi everyone welcome back to another video and today we’re talking about one of our favorite medications spironolactone and many of you may know that spironolactone is used as an androgen receptor blocker in people undergoing a feminizing transition so oftentimes it’s not enough to just have hrt through estrogen or progesterone you oftentimes have to suppress

Androgen activity in the body using spironolactone to inhibit the triggering of androgen on androgen receptors but one of the most common complaints that people get with spironolactone is that they have to pee all the time and this is actually not really a side effect because spironolactone is also primarily used as a diuretic specifically a potassium sparing

Diuretic in people with high blood pressure or who have issues with their potassium levels um so today we’re going to talk about how spironolactone makes you pee a lot and how it contributes to your water balance because with a diuretic you are going to be excreting a lot more water and you’re not going to have water in your system it can cause you to be dehydrated

Very easily so we’re going to talk about how exactly this happens what is the mechanism of spironolactone how does it cause you to pee a lot and so i’m gonna address the picture um to the side of me this is actually a nephron this is the functional unit of the kidney yes this is a kidney it’s not the best drawing but i hope that it makes enough sense uh for this

Kind of explanation so we have here the different areas of the kidney i’m just going to walk you through this briefly before we go in depth in a specific region of the kidney and here this area over here with this little mess of red is the glomerulus this is where blood is filtered it comes in through this afferent arteriole it goes through this big mess here blood

Gets filtered the stuff you’re filtering out it’s going to go in here into this tube and then the blood that has been filtered is going to leave via the efferent arteriole and then you get the filtrate that’s going to move through the proximal convoluted tubule it’s going to go down and it’s going to go through the descending loop of henle up the ascending loop

Of henle and then it’s going to go through the distal convoluted tubule and then back out the collecting duct and by the time it gets to the collecting duct all the stuff you want to reabsorb is usually reabsorbed you are going to reabsorb some stuff in the collecting duct as well but by the time it gets to the collecting duct it is urine you are going to excrete

It and not deal with it anymore so when we’re talking about spironolactone and diuretics we’re going to be focusing on the collecting duct this is the part that it acts on and the part where aldosterone acts on and we’re going to talk about this in some detail so let me take you over to our next picture and there’s a mechanism that we need to talk about in terms

Of blood pressure regulation because this is how we are going to produce aldosterone aldosterone is what is going to be inhibited by spironolactone so we’re going to walk through this pathway really quickly so there’s a type of organ in your kidney in fact in your collecting duct that is called the macula densa this is part of a system called the juxtaglomerular

Apparatus and that’s a really big name but it just means that it’s right next to the glomerulus and what is the job of the macula denso well its job is to sense sodium levels in the filtrate that’s going through and this tells us something because water follows salt so if you have a low concentration of salt compared to water it means you have an excess of water

In that area and it probably means that you are peeing out too much water and you’re at risk of being dehydrated so in order to save your blood pressure and keep your blood pressure in a good range um if your sodium levels in the collecting duct get too low we’re uh going to assume there’s a lot of water we’re going to try to keep this water as much as possible so

The macula denza is going to secrete a hormone called renin and then renin is going to travel kind of in the blood and then there’s another compound that’s released by the liver called angiotensin and angiotensinogen is going to be converted by renin to angiotensin 1 and then the lungs actually are going to produce angiotensin converting enzyme which is going

To act on angiotensin one converting it to angiotensin ii and angiotensin ii is going to have a whole other mechanism of blood pressure regulation we’re not going to cover angiotensin ii today we’re going to cover aldosterone but angiotensin ii is a stimulator for the production of aldosterone which is why we have this whole pathway here angiotensin ii is going

To travel to the adrenal gland yep the adrenal cortex we’ve covered this before it’s going to go to the adrenal cortex and it’s going to stimulate production of aldosterone and if you want to see that whole pathway i’ve made videos about production of aldosterone in the adrenal cortex but that’s not important i’m going to assume you already know how that works but

Anyway we get aldosterone production and we’re going to direct our attention back to the collecting duct so we have cells in the collecting duct we’re just going to have one cell here so imagine that we’ve zoomed in really close on this collecting duct picture that we saw before and we just have one cell here and there are two membranes here we have two openings one

Is the inside of the collecting duct where the urine is passing through and then we have the other side where there’s a blood vessel and this is where blood is passing through so when we are reabsorbing water our goal is to try to move the water from the urine into the blood so it has to pass through this collecting collecting duct cell and this is where aldosterone

Is going to come in to help us make this mechanism possible so aldosterone is going to travel inside the collecting duct cell and it’s going to bind to a mineral corticoid receptor and i’m listing it as the aldosterone receptor aldosterone is a mineral corticoid mineralocorticoids are the broad category that aldosterone fits under but just to make this easier i’m

Putting the aldosterone receptor so aldosterone is going to travel into the collecting duct cell it’s going to bind to this aldosterone receptor and it’s going to upregulate so when i say upregulate it means it’s going to stimulate the activity of two types of res well one type of channel uh one type of active uh transport mechanism and this channel is enac uh

Enac is a sodium channel on the apical membrane so the side near the urine and it is going to allow for sodium to travel into the collecting ducts so aldosterone is going to stimulate more of these channels to be on the membrane so that more sodium can come through into the cell and then we need another mechanism to move the sodium from inside the collecting duct

Cell into the bloodstream so we have this uh molecule of atpase it is an enzyme and it’s an atpase because it uses energy from atp in order to pump sodium into the blood but here’s the thing with atpase we’re not just gonna pump sodium into the blood we’re actually going to do an exchange so every time we exchange sodium into the blood we’re going to bring out a

Molecule of or an atom an ion of potassium so this potassium is now going to be moved from the blood into the collecting duct cell and then it’s going to go through its channel out into the urine so we are bringing in sodium and we are kicking out potassium and what we’re doing here is we are creating gradients so we’re creating a sodium gradient we are increasing

The amount of sodium in the bloodstream because as i said before water follows salt so the fact that now we have sodium in higher amounts in the blood the water is going to flow from the urine into the bloodstream right so we are getting uh water to follow the sodium into the blood we are increasing the amount of water in the blood we’re increasing our hydration

Status we are increasing our blood pressure okay so now that we understand the mechanism of how aldosterone works on the collecting duct where does spironolactone come into play and this is pretty simple once you understand this aldosterone mechanism spironolactones pretty easy to understand so spironolactone is a competitive antagonist of the aldosterone receptors

So competitive antagonist means that essentially aldosterone’s going to try to bind to this receptor and spironolactone is going to come in and it’s going to kick it out of the way and say nope this is my spot now i’m going to take over so spironolactone is going to bind to this aldosterone receptor and i’m going to draw this out so that we can go through it kind

Of step by step because i didn’t want to overwhelm you all with this mechanism how it’s going to reverse things but spironolactone is going to boot aldosterone from the receptor it’s going to say nope you can’t bind here and so we’re not going to upregulate these receptors so we’re not going to allow enacts to really have some activity so if we don’t have enac

Sodium is going to move out of the cell sodium is going to go that way um same thing sodium is going to move that way there’s a more complicated mechanism we’re not we’re not going to reverse an atpase per se but it’s not going to be as functional so we’re not going to be pumping the sodium out so you’re going to get sodium kind of building up uh in here it’s

Going to leave and go into the urine you’re going to have more sodium in the urine and likewise we’re not going to have this potassium leaving potassium is actually going to be spared and this is why spironolactone is called a potassium sparing diuretic because we are saving potassium from leaving we are keeping the potassium and we’re getting rid of the sodium

So if water follows salt if water follows sodium then if we boot the sodium out of the cell then where’s the water going to go absolutely right the water is going to go out into the urine and the water is going to be peed out so you’re taking the water that was in your blood so this water here that was in your blood is going to move it’s going to be kicked out

Into the urine and it’s going to leave so now think about these volumes if you have water leaving in high amounts you’re probably at risk for dehydration so be careful uh if you’re taking spironolactone you need to watch your hydration status you need to make sure that you’re drinking enough water and because you’re more likely to pee it out so make sure that

You’re staying hydrated and then also with potassium we know that potassium can cause arrhythmias hyperkalemia can cause some problems with your heart so be conscious of that you are keeping higher amounts of potassium you’re going to be more at risk for arrhythmias so if you have a heart issue where you’re prone to arrhythmias you might not want to be using

Spironolactone that might be a reason not to use this as an androgen blocker so kind of take this into account this is just one mechanism of how spironolactone has some side effects take all of this kind of um at your own discretion think about if this is a mechanism that you’d want to deal with as a side effect but also it’s kind of a cool mechanism i think the

Kidney is fascinating i think this hormone interaction is really cool to study and i hope you all liked it too and i’m going to cover more drugs in the future talk about their side effects talk about hrt and that kind of thing but i hope you like this video and i will see you all in the next one you

Transcribed from video
Why Does Spironolactone Make Me Pee? By Student Doctor Ben