January 26, 2023

Introduction to diuretics and the mechanism of action of loop diuretics (furosemide).

Diuretics are medications that promote diuresis and dyna recess is the excess or increased production of urine so in this video and the subsequent videos we’re going to discuss a number of different types of directs we’re going to talk about where they act and how they act in order to promote your output now there’s a number of reasons why we use diuretics from heart

Failure to hypertension to liver diseases and sort of kidney diseases but we’ll discuss those where appropriate within this course so first i want to talk about the three categories of diuretics now there’s numerous category of the directs but for you i want you to just remember these three particular categories those categories are the loop diuretics the thiazide

Or five my life dynamics and what we call the potassium sparing directs alright so what we’re going to focus on is one at a time so on a first look at loop directs now because diuretics promote diuresis which is the production of urine these substances obviously work at the kidneys now if we want to talk specifically about where in the kid is the zero production

Curve you should know that the terms of the net on there for these i relics tend to work at the nephron but you also know that if you were to draw an f r there’s different aspects of the note on now i’m going to simplify that one for you you don’t have the glomerular capsule you’re gonna have the proximal convoluted tubule now i haven’t drawn a convoluted i’ll

Just draw it straight for simplicity sake you’re going to have the descending limb of the loop of henle then you’re going to have the ascending limb of the loop of henle and then there’s a sick portion of the ascending limb of the loop of henle then there’s a distal convoluted tubule and then we ultimately hit the collecting belt and as you note blood that comes

In each kidney has 1 million of these mesons and there’s going to be this capillary that are present now i don’t have a red pen that ever this is a compiler which looks like a ball of yarn here an equal amount of calcium and that’s called the glomerulus and you can have blood coming in and it gets filtered into the glomerular capsule and not just a plasma but

Also what’s within that time map so that’s going to be the water the electrolytes that wastes and so forth because they get filtered through them and travel along this meson and if they stay within the lumen of this tube the hollow inside ultimately it comes out here at the end as pit simple we know that we filter approximately 200 liters of this blood every

Day but we don’t pee out 200 liters of fluid we care about 1% amis at two liters so what happens well obviously the substances that are within this aluminum must get thrown out back into the body so the reason why i’m recapping this for you which is the basic renal physiology that we’re paying through last year is that you need to be aware that when we go through

The diuretics we’re going to act at different parts of this mess and they’re going to throw certain substances back into the body or they’re going to tell certain substances to stay within the tube now predominantly the way these diuretics work is by telling the sodium to stay within the lumen of the next one why because if sodium stays within the lumen of the

Nephron you should know that where emersonian goes water follows so sodium stays within this net fine it pulls water in with it and therefore more urine output that’s basically how these diuretics work but because they act in different areas that is slightly different mechanism of action even though predominantly they work by keeping sodium within this tube and

Therefore pulling water in so like if it the first one i want to talk about the link sirenix so hence the name the loop diuretics act at the loop of henle in this aspect here but specifically i want to talk about the loop directs that at the thick ascending aspect of the loop apparently so i’m just going to wipe this out and draw a lot larger for you so you clip

The glomerular capsule with a proximal convoluted tubule get the descending limb your di can mingle in and then let’s show the kick aspect really large so that we can hole up what happens the distal convoluted tubule and we’ll just leave it there now remember i said when things get thrown out it goes back into the body so when i draw an arrow coming out of this

Tubular that’s going back into the body but because this is a – but they’re all lined with cells so i’m going to join i see cell coming off the side of this ck sending linen hanley okay therefore things will go from the lumen to the cell back to the body or from the body to the cell back into the movie to be paid out and we’ll highlight that first thing you need

To be aware of is this all the cells of your left on okay so all them cells are just blown up one here have at the basolateral side okay this is the luminal side of that cell because over halloween fun this is the basolateral side okay they have embedded in their walls pups all one of these pumps do these parts will flow out free sodium and hopefully are the rest

Of it and throw back in to potassium so i’ll just draw to be nothing like that okay you know that this uses atp and therefore it’s called the sodium potassium atpase pump you notice there are three sodium out to potassium back in i just wanted to highlight that to you first because all the cell types will have this this is how we get the sodium that into our body

You can clear that there this is why so institutes put on the extracellular a plant cell what happens it’s feature cellular inside the cell now next thing i want you to be aware on is remember how the blood come occur and we filter all that stuff from our blood let’s figure it out the ions what ions will be filled up well we get a filter a huge amount but let’s

Focus on the major ones we have a filter sodium potassium magnesium calcium and chloride there’s others such as hydrogen ions and so forth but let’s just stick with those at the moment which means when they get filtered through they’re going to travel through unless they get pulled back into the body okay so that means as they travel through what are we going

To get when they reach deep a sindhi a thick ascending limb of the loop of henle well we’re going to get so i’m just going to get here potassium is going to get here magnesium is going to get here calcium is going to get here clora is going to get here all right remember i said 99% of this stuff is thrown back into the body so let’s talk about that this is what

Happens normally well on the luminal side of the cells of the thicker sending with the henry you have a really big part another part what this part does is it throws one sodium into the cell from the luminal side it throws one potassium in from the liminal side into the cell and it throws two chloride out of it this pub is called the sodium potassium to chloride

Pump or the sodium potassium to chloride simple double co-transporter okay all right what does this mean simple sodium has gone from the luminal side into the cell then what are the dirt while travel over to these so excessive atp is popping it’s thrown outside perfect without happens well the coroner comes in it chloride channels in the walls here and therefore the

Chloride travel that as well what i’ll tap it where you can see that potassium is coming into the cell from the little side coming into the cell from the extracellular fluid to have a huge increase of potassium here so that means potassium once we get out somehow right the cells don’t want to continually increase all this concentration of potassium how does it get

Out well couple ways one way is that there’s some channels for potassium and some potassium will work out it’s not a huge amount the main way that potassium gets out is this channels here and the potassium remember potassium is accumulating you can take potassium coming into the little side potassium coming in from the extracellular side and increasing increasing

Increasing and potassium begins to listen to the little side okay and so because it’s in creating a huge amount and a huge amount leaking out so you start to accumulate all this potassium because you’ve got a high concentration gradient of potassium here and it gets so now these are very efficient so not much potassium goes to the extracellular fluid i’m not going

Into the learning now what have we done with these i’ll come in the sodium that’s come in or that was easy you’ve got thrown in through the sodium potassium to chloride pump and then got pumped out by the sodium potassium i do clio therefore sodium’s dealt with perfect what about chloride well quad came in through the same sodium potassium – for our pump and then

Diffuse out through qualy channels so let’s go dealt with well rather than attacking well what we’re going to have is all this potassium starts to increase inside the lumen of the cell why because some potassium is thrown in and then some more potassium so in and then it diffuses back again and you’ve got a really really positive charge sitting in the lumen of

Your nephron at the thicker standing leg what do you think that means for paul magnesium calcium look at magnesium calcium they’ve got two positive charges each so you’ve got this really positive signal going on here in the lumen of the big ascending limb do you think magnesium chloride like this i hate it so what do you think they know they were killed by it and

They know what i’m out of it and that is push their way through the cells and get back into the body same goes with magnesium magnesium doesn’t like that it’s pushed out goes back into the body so what have we done effectively this is what happens normally inside of you and i is that when we bricks the thick ascending limb the sodium potassium magnesium calcium

And chloride that have reached their knees in goes back into the body calcium goes back into the body some potassium goes back into the body chloride it back into the body and slowly goes back into by the perfect that’s how we’ve reabsorbed this is one part in which we’ve reabsorbed the glute number of these vials now let’s talk about diuretics and let’s talk about

Specifically loop diuretic so the loop diuretic that we need to talk about today is fried light also known as through the mind now how to desire it work simple this diuretic blocks this sodium potassium bike ride putt it no longer works just think about what that means okay if this sodium potassium dunk or i can’t know underworks it means that so neela comes in

Does it go into the cell right that means sodium accumulates here in the women it means that potassium that floods through and here does it go in some potassium accumulates here it means the chloride that comes through doesn’t get to go to the cell and chloride accumulates here now think about what that means that means that positive sodium ions potassium and

Negative chloride now i’ve got a nice sort of balanced charge here what that means is because there’s no potassium building up here and no sodium sodium can exchange for capacitors and we don’t have that potassium building up inside the cell which means we don’t get that either lots of potassium into the lumen so that’s what happened we have this nice positive

Positive negative negative balance charge attacking in the lumen which means when magnesium and calcium get here they’re not repelled they do not jump out of the cell and if they don’t jump out of the cell when you think they accumulate they accumulate here in the lumen of the center of the thick ascending limb of the nephron now you understand how else moses works

So that means that where there’s a high concentration of these ions it pulls water in towards it and this water will eventually go through the neck on a big-kid out and that’s how far is amide works of a diuretic it also means that if patients take this long term they’ll get to absorb much sodium in them back into their body they don’t get to absorb much potassium

Or chloride or magnesium or calcium and then can actually be become over a long period of time revisions direct deficient in any of these particular clients so that couch rose amide works as a direct

Transcribed from video
Diuretics – loop diuretics (furosemide) By Dr Matt \u0026 Dr Mike