LECTURE 10

In the series in Port 143 the lecture today we're going to be moving a little bit

further down the nephron. So we've already gone glomerulus proximal convoluted tubule

Loop of henle. We're now getting towards the distal convoluted tubule and the collecting

duct and we're going to be talking about the Management's of electrolytes and water

balance. So again some of this you may have heard of before as a part one is a lot

of Basics. We're going to be covering anybody that did the Endocrinology unit. They

will do that one.

Okay, great. So you'll have heard some of this before but hopefully there's some

new stuff in there as well.

Okay, so let's think about today's lecture. This is what I hope to do. We hope to

cover look at the renal turnover of sodium. Think about the roles of ADH we talked

about that last time that I'm also going to pick up on another hormone ANP.

Also going to talk about aldosterone. So you've all heard of rath the renin-angiotensin-aldosterone

system. I did mention it in the earlier lecture and I'm going to come back to that

and talk about its role in fluid and electrolyte balance I think about first

Where that comes in and sweating and I'm also going to give you some examples of

different directrix talk a little bit about their mode of action and then finally

just talked about the concept of fluid rebound which can happen. Especially people

are taking diuretics for during dieting.

Okay, so we'll know the main function one of the main functions the kidney is to

regulate sodium and or electrolytes and water balance. We all know that the plasma

osmolality should be about 300 290 300 milliosmoles per kilogram of water. I've

already talked about what happens in the proximal convoluted tubule we get bulk

reabsorption of sodium.

As I move down the descending limb, we don't get any movement of ions. We're going

to get the secretion of urea and the reabsorption of water as we get towards this

side. So the ascending limb you said earlier we get n KC c 2 on there the sodium

potassium and two chlorides transporter allowing the reabsorption of those Ines

and then we get the distal convoluted tubule here. We still have some sodium in

the filtrate and it's we have some

Water obviously, it's slightly hypotonic to proximal convoluted tubule.

So it's here where we want to think today about what's happening to the sodium electrolytes

and also the water.

So here's our case study for today Miss after go.

I have to go is 22 years old. She's noticed recently that she's quite tired. I left

with time. She's

not changed her daily routine, but she's noticed that she doesn't have much energy

blood pressure is quite low at the time. It was measured during a practical class.

It was 90 millimeters of mercury brother her systolic over 46 millimeters of mercury

for her diastolic not only usually loafer female but lower than she expected to

be

she's noticed that when she stands up Suddenly so she's been sat down or lay down

and she gets up Suddenly. She feels very lightheaded.

She went to a GP did some blood tests and he noticed that her potassium levels were

quite low plasma so she had hypo anemia.

And she's also producing large amounts of dilute urine. Okay. So by the end of today

hopefully work out what's wrong with Miss up to go.

She's also recently noticed that she's always trying to watch your weight, but she's

noticed that weight. She seems to have lost a few pounds, which she's not unhappy

about that again. She's not been trying to lose the weight desperately, but this

is one of things.

Okay, let's talk about so pollens done. Electrolyte salt balance sodium is the most

abundant iron in the exercise of fluid. We all now know that it drives secondary

active transport. So it's essential for the movements that in the proximal convoluted

tubule. We have Transporters couple two amino acids to lactate to glucose. Okay?

we actually

require sodium in the diet. The guideline daily amounts would recommend about 6

grams of sodium a day, but we actually only need about four does most of us know

certainly for food. It does make it more palatable. If you have salt in your diet,

it does tend to make things taste because it's a steal.

So normally our salt intake can be up to 10 grams, which is over the guideline amount.

Most of us should take in and said about for the guideline amounts are usually about

6 grams per day, but most of us tend to overdo that

Once inside the body homeostatic mechanisms, try and maintain a balance of sodium.

So any that we don't require any excess. We will lose either by sweating in the

urine or in the feces and majority of sodium comes out in the urine. Okay, and that's

sodium and chloride.

However, sometimes it was sweating more than we should or producing more urine some

fans of this is artificially we're doing exercises were losing through sweat. We

can actually cause an imbalance of sodium and this is what we're going to think

about today.

Okay, so there is a hormone that helps us to control the amount of sodium that's

lost.

from

your insect controls the amount that we reabsorbed back into the plasma. Does anybody

know the name of it?

Aldosterone well done. So all those drones actually one of my favorite hormones.

Everybody should have one.

I lost Throne is a steroid hormone and many moons ago. I did some research looking

at the effects of aldosterone in a medullary collecting ducts.

So it's always been very close to my heart to think about your favorite hormone.

So is that although strong is a steroid hormone. So it's produced in the adrenal

cortex from cholesterol and the concentrations in the plasma tend to be quite low

give me some of that there is normally produced if we have an increase in potassium

in the plasma or we have a full in sodium.

It's actually more sensitive to potassium than sodium but it tends to be known for

its actions on maintaining sodium balance.

It stimulated by Angiotensin 2. That's where it forms part of rust. So the renin-angiotensin-aldosterone

system and it's inhibited by this hormone ANP, which I'll talk about a bit later

on.

If sodium lost becomes so severe then sometimes the posterior pituitary gland can

kick in and release.

ACTH just got a trophic hormone, and this will stimulate its release further. So

we should normal violence is through child and attentive to but sometimes if there's

been dramatic sodium loss then this will kick in as well. So we'll see.

So there's a summary of its main functions if it's retaining sodium. It's also going

to retain help to retain water.

Okay, remember sodium moves and water will follow.

Main site of actions will be the collecting duct, but also the distal convoluted

tubule.

Okay. So right back at the beginning I spoke to you about the renin-angiotensin

system. So here's a little reminder. We have specialized cells that sit around the

afferent arteriole that can detect changes in pressure the stretch receptors.

We've also got this area here. That is so convoluted tubule known as the macula

densa and this has a sensing capability so it can detect changes in sodium levels

and also osmolality

So what triggers the renin-angiotensin system can either be a for in blood pressure

through the afferent arteriole or a change in the concentration of sodium within

the macula densa here? So both of those things can trigger the renin-angiotensin

system. It's actually much more sensitive to changes in sodium.

As a changing of multi by about 2% will trigger this where as a fallen blood pressure

pressure of about 10% is much more sensitive to the ionic changes than it is to

the profession.

okay, can we think of some instances where blood volume plasma volume made for can

anyone think of instances see in everyday life when your blood volume your

made for

Okay, that's probably one of the key ones dehydration if we don't drink enough fluid

plus 1/2 is our plasma volume will start support the lack of water if you've got

severe diarrhea travelers diarrhea.

You're losing a lot of fluid that way all you've been sick. So you've got DMV diarrhea

vomiting then you're going to find that your blood volume because involving will

start to form if you've lost a lot of blood through hemorrhaging even is some sort

of trauma again plasma volume of for if plasma volume Falls and your blood pressure

is going to fall, okay.

So if blood pressure Falls that can be detected by those cells in.

The granular cells that release renin so they could be detected around the afferent

arteriole. There also will be some changes potentially in your osmolality which

we picked up by the macula densa cells.

So a change in pressure in the afferent arteriole will be detected this then causes

the release of renin also known as renin.

Because it's only got one end not to be confused with reading that we find in the

GI tract and stomach. So renan also known as renamed will be released.

What it does is it's an enzyme.

It's released into circulation.

Now as we're sitting there.

Our livers are producing something called angiotensinogen angiotensinogen is an

inert large peptide doesn't do anything on its own but when it comes into contact

with running running stops the end of it so it becomes Angiotensin.

Saran indeed an enzyme

will activate the angiotensinogen by chop it into bits and it becomes Angiotensin

one and you tend to want again doesn't have many functions and you're tensing one

when it comes into contact with a specific enzyme known as Ace, which is angiotensin-converting

enzyme it will then be converted to Angiotensin 2 and all spoke to you about managing

the marrow filtration.

I'm just sensing to have lots of properties. It's a powerful vasoconstrictor so

it can cause vasoconstriction in a lot of the blood vessels in the body.

But it can also trigger.

ADH release from the fleshy from the posterior pituitary so we can get release of

ADH posterior pituitary which will cause an increase in water re-absorption in the

collecting duct and intense into can also stimulate the adrenal cortex to release

aldosterone which will help with the reabsorption of sodium.

If we get more sodium being reabsorbed.

Then water will follow and the blood volume will return to normal.

If you think back to blood pressure control.

blood pressure recalls

sometimes is gone.

If we increase the peripheral resistance by vasoconstriction, we're going to increase

blood pressure.

So by increasing under tension to release we're going to increase those of constriction

and therefore increased peripheral resistance, which will help to increase your

position. So this system is really good to fold in increasing blood volume.

Resuming blood pressure to normal values and also helping with basic constriction

to maintain blood pressure.

Okay.

So how does aldosterone work but its main site of action as I said before it's distal

convoluted tubule and the collecting duct it acts on several Transporters in the

renal system.

One of the main ways that it increases sodium reabsorption is it increases the expression

of Enoch? So the epithelial sodium Channel?

It also stimulates the sodium-potassium atpase and if you think about it, that's

really helpful because if we stimulate that we're going to get more sodium being

pumped out of the cell through active transport. So the concentration of sodium

inside the cell is always going to be low and therefore we've got that driving force

for sodium to enter the cell. It's going to be reabsorbed more effectively.

It can also stimulate the sodium proton pump again to increase the amounts of sodium.

the cell in exchange for hydrogen

Okay, so that's aldosterone so that one only impact sodium.

But it can also help with balancing blood pressure.

Water re-absorption is a follow on from that but also to the stimulation of ADH.

So let's take another hormone that affects sodium reabsorption. So we've had our

dosterone. There's another hormone called atrial natriuretic peptide it heard of

that one before. Okay. This is a peptide nature etics a straight away. You can see

it Alters sodium see that's where DNA comes from and so it

The chemical symbol if it's produced in the Atria that's been produced in the heart.

And this is why this one was named.

So a true nature etic peptide is

a peptide that's produced in the heart in the Atria and it's produced when the blood

volume goes up. So if you have an increase in blood volume as the Bloods passing

through the heart join the cardiac cycle, you might get stretching of the Atria.

So as the Atria stretch because of that increase in blood volume ANP will be released

into circulation.

It will then continue to travel around the body until it reaches the kidneys when

it reaches the kidneys. It has actions to increase sodium excretion by the kidneys.

Okay within the collecting duct the distal convoluted tubule.

Mainly the collecting books here.

So by causing more sodium to be excreted water will follow so what's going to happen

to blood volume.

It's going to come down. Okay, so this is almost working having opposite effects.

Well the stroke ANP also inhibits ADH secretion and posterior pituitary. So it's

stopping water absorption. Which again is helping to get rid of that excess fluid

And it also inhibits Angiotensin 2 and Ultra. Okay. So this is how we get that balance

of sodium with ANP and also aldosterone.

Okay, so more clinically.

Over the last 20 years. We now know much more about these nature attic peptides.

So originally was only a MP H 1H etiquette. I produced in the heart. We now have

a b type a seat type and the d-type that's been identified. So these are all really

similar in structure. They're very similar kept side chains.

however

slightly different

so the b-type was originally it's nothing to do with the political party. The beef

type was produced in the brain. It's found in the brain. That's why it's called

Beto.

But we now know that the d-type nature attic peptide is highly concentrated in the

ventricles particular the left ventricle.

So because of that and we see an increased level when we have great concert patients

with congestive heart failure. So it's an early indicator in some milder cases apartment

that can be detected so it can be used as a diagnostic tool.

So the person who's undergoing?

congestive heart failure

the PNP levels will rise and again, it's a simple blood test that can be done to

see whether or not the heart is failing. So I put here there's different types of

heart failure. You may have come across them before anyone that does cardiovascular

systems in the third year. They come back to this just a reminder that congestive

heart failure can happen if you got a problem with

Your ventricles they can't push the blood out as they should do. So you've got any

issues with contractile apparatus in the heart or if you've got a problem with the

valves if the blood's not going out as it should what can happen is you get increased

pressure in the Atria which can then back up its the pulmonary system.

So that can be taught we call from left. I decided heart failure. Eventually. We'll

get a backup in the pulmonary system and that can then further lead to a backup

within the systemic circulation begin increasing pressure in the systemic circulation

from the pulmonary circulation, which can then lead to right side.

That's not cool Crush missing you reading the BNP is used quite routinely now as

a way of detecting suddenly milder cases congestive heart failure. Sometimes though

things can cause it to increase so we can get an increase with age females tend

to have higher levels. There's lots of reasons there. We can decrease our BMP levels

with some of the following so there some directrix. I'm going to talk about in a

while. So you've always got to be wary and look at a patient as a whole.

Oh and see if there are any medication look at their sort of gender age or their

medical conditions to see if they could also be impacting on these test results.

I didn't mention cnpc. The CNP of originally was thought to be centrally released.

It has been shown to be released by Converse i'ts so we moved in bone and also endothelium

cells of look vessels and the neural one dnp.

Has actually been shown few few years ago now but it was actually shown to inhibit

l-type calcium channels within the ventricles. So in again, it's having some role

in modulating contractile activity within the ventricles again. It's still not as

clearly known. This one isn't slow defined as the others but they're all quite distinct

the whole thesis there on a true nature.

Okay, so over hormones that can also impact sodium levels.

There's something called Euro Dalton and this is very similar again instructed to

AMT, but it's not one of the atrium atrial natriuretic peptide.

It's secreted by the cells of the kidney. Okay, so it's actually secreted by the

kidney has a higher potency than NP. This one was first is going to think about

1994 not that long ago and it was identified within human urine that's quite a recent

ish 130 years ago. We can also get alterations sympathetic nervous system that can

also ulcer

sodium balance

Adrenaline noradrenaline can actually stimulate sodium reabsorption again, this

is sort of an extreme which would happen over time. But again, it can be seen.

Dopamine can also have an effect in some studies to show that both the catecholamines

here and dopamine can also be used in conjunction which makes sense because this

is stimulatory. This is more like to be returning to normal.

Finally, there's another hormone there that's been picked up called Uruguay Ellen

and this is produced in a small intestine. This one was identified because it was

noted in experimental models when you ingest large amounts of sodium.

Then it more is secreted and released in the urine than when it's injected IV. So

there must be something within the GI tract that's actually enhancing.

the levels of sodium

okay are altering the levels of sodium within urinary system. So that's when they

were that from came from so you may come across these in your reading.

Okay, let's move on to water. So we've talked a lot about ADH lust week. We know

water view of you with your water bottles. It's a universal solvent and it's required

by the body.

We normally get most of our water intake from drinks from fluid. We do get some

food which is often forgotten and we can produce water through water oxidation.

I said right back in the first lecture that

Usually about 60 percent of our body volume is a body weights is water which equates

to about 32 to 40 liters. But remember the amount of water that we take in if the

body doesn't need it. All it does is gets rid of it. So it's really good to maintain

hydration really good to make sure that we're constantly keeping those fluid levels

tops off. But any that we don't require we will use and we will lose in the urine

or we can lose it through our stool samples.

Through sweating of your spiritual losses, but as the environment changes to proportions

that we lose May differ.

So again, that's back to that slide. I showed you a while back showing where in

the body we have fluid and it's really important that the plasma maintains that

fluid level.

Remember that if we expose ourselves to a very dilute so the plasma becomes too

dilute to hypotonic. Then what can happen is water will move from the plasma into

the cells and the cells as well if the plasma becomes more concentrated and what

will happen is water will move from the cells into the plasma to try and maintain

homeostasis and the cells will shriek.

Okay, so we know about ADH you're all aware of what happens with ADHD talked about

that last time but how does the body know that we need more fluid? How do we know

when we should drink and when we should top or for water levels? Well two things

that we do we have a thirst mechanism and we sweat.

So, let's see how this works.

So, how is the external fluid?

Controlled so remember the sodium and water we said before what you put in will

come out. We're always trying to maintain balance.

When we sweat when we sweat initially so you're sweating is because you're in a

warm environment or maybe you've got synthetic Innovation. That's making you sweat

because you're a bit nervous initially that's going to be mainly water with a little

bit of salt in them little bit. Okay, mainly water them.

It's going to be hypo osmotic quite dilute fluid and initially.

As I said, this will be the initial response. What's going to happen if you sweat

for a length of time is you're going to have a slight fall in your extracellular

volume in your plasma ball.

You should know by now that if you lose fluid mainly fluid your osmolality is going

to increase.

So the concentration of the plasma is going to increase.

Okay, so that's initially if you're at the gym and it's really warm, you've got

a drinking you sweating quite profusely or as I'd like to think you lay on the beach

somewhere really warm or you've decided to run a half marathon in the desert somewhere.

You're going to start sweating quite dramatically. Okay. It's going to be more than

just that little bit of sweating because you're in a warm environment or you doing

a little bit of exercise so over time what's going to happen is as the plasma volume

starts to fall.

further

osmolality is going to increase we're going to get stimulation of our old favorite

the renin-angiotensin system.

Fall in place and volume will also GFR the body will try and maintain GFR by the

renin-angiotensin system loose spongy sensing to which we know affects the afferent

and efferent arteriole.

We'll get the stimulation will get the production story of aldosterone which will

cause the reabsorption of more sodium. So as we're losing sodium that will be picked

up. We'll get more sodium being reabsorbed Gibby.

As osmolality increases because you losing fluid you are losing some salts. Well,

we can still going to get a higher of novelty than I do. So you're going to get

stimulation of ADH. And again that's through the renin-angiotensin system. So the

body's going to try and reabsorb more water and salts. So if maintain that balance

of normal osmolality

Okay.

So the effects of this is we're going to alter sodium excretion of kidney. You won't

be losing any sodium. We're going to try and reabsorb what we can but if your sodium

levels are still reasonable. We're just going to make sure that we don't lose any

further sodium through the kidneys. So you may be losing it to the sweat, but the

body will try compensate by losing less at the in Europe.

And ultimately this will help to balance.

the plasma

you might have noticed that if you ever had extreme sweating you can probably taste

the salt either on your lips or even on your hands. You can soften taste that the

sweat is actually really quite quite high focus on the hypersonic.

Okay, so as we continue to sweat we start to lose more salts that way and again

that's another way that the body is trying to lose that excess and rebalance the

plasma osmolality.

Okay, what about thirst? Well, if our blood volume Falls because we're dehydrated

again. The osmolality is going to increase that's going to be detected by our osmoreceptors

and our pressure receptors.

Pressure receptors there. The baroreceptors are all aware of in the cardiac system.

We've also got pressure receptors.

Those granular cells the afferent arteriole that going to detect changes in blood

flow to the kidney.

This is going to stimulate and you send some to through the renin-angiotensin system

I mentioned before so we'll get the production of running running or calls and he

sends an urgent become Angiotensin one and you're sensing one will be converted

to Angiotensin 2 by the ace enzyme and Angiotensin 2. Well first of all stimulate

Aldosterone ADH or there's other things but it also stimulates the centers in the

hypothalamus.

a great little compound and now I find interesting is

When we get that first, we've all felt thirsty at some point. Have you ever noticed

that you drink and you stop feeling thirsty before this time for that water to get

into your system. So that tells us that we now know that there must be some sensing

mechanism in the pharynx that actually feedback to sell the body to stop drinking.

So normally when you quench your thirst in your mouth and your pharynx does then

some sensing mechanisms the stops you over-hydrated.

Yeah, so actually when you stop getting thirsty for be a good time to stop drinking.

Okay, and again we can get changes now, Das drama can also help to rebalance with

increasing sodium reabsorption and water will follow

Okay, so let's move on to the second part now. So we've talked a little bit about

sodium and water balance in the hormones that can control that and I want to talk

through some diuretics now. Hopefully you're done some pharmacology before.

The well instructs molecules to answer some of them there, but hopefully this will

review those for you. So a diuretic is anything that can increase the excretion

through the renal system of water and solutes.

So anything that can increase diuresis increase urination.

The main clinical uses are they can be used as treatment of hypertension. So by

increasing urine output, you can help to reduce blood volume which can help to reduce

blood pressure. So some people take diuretics or director type drugs as an antihypertensive

treatment.

Could also be used for people with congestive heart failure. If you've got pulmonary

hypertension, so you've got congestion within the field of pulmonary edema, as you

get fluid. We've pushed out and since tissue fluid again diuretics are really useful

in getting rid of excess fluid people with swollen ankles people with swollen breasts

again, get rid of those that excess fluid

Again, some of heart failure in order to reduce the pressure on the heart. It can

reduce the blood volume which can help with that.

So a common mechanism is to alter sodium because if we stop sodium reabsorption,

then we're going to stop water absorption. Okay, so a lot of them a lot of diuretics

work by blocking sodium in some form.

There are also about oh

these non-clinical diuretics that also have an impact on urine output so we can

categorize our diuretics into non clinical and clinical. I'll give you some examples

now.

Okay.

Non clinical directors. These aren't treatments. This isn't any drug. You're not

taking anything, but this is just what can happen naturally if you like if you've

got increase in blood volume, we've talked about this before your blood pressure

will increase

Sometimes that can increase the amount of the pressure going through the body's

trying to maintain a current efferent arterioles are trying to control the amount

of pressure coming through the glomerulus. But sometimes that is overridden and

your blood pressure is so high you're going to force the filtering as you go through.

You're going to find that the fluids moving faster through the nephron and you may

find you get what we call a washout. You don't get for reabsorption of solutes that

we need and therefore more solutes will stay in the filtrate and walked over Romania.

Do you think that we can see is water diuresis? So if you drink lots of fluid, did

you drink couple of pints of water?

Shortly after you're going to find that you need to urinate and that's simply because

by increasing your water intake you're going to inhibit any Aid excretion and that

or you just going to pee out that existed. That's another way to make you urinate

sister drinking.

Yes, you've got to provide a urine sample to the doctor tops. It drinks and go before

I give it half.

Okay, so diuretics usually The Clinical Director 6 would usually act on specific

membrane transport proteins. I say usually because there's one example that doesn't

work you do that. So we look at our nephron. And again, this is quite nice diagrams

test yourselves. Think about I'm going to Nate name some now, and I'm going to talk

through them. So we've got something called Carbonic anhydrase Inhibitors. These

can act here in the proximal convoluted tubule.

Sighs I die retic that maniac to the distal convoluted tubule. We've got osmotic

diuretic that mainly act in the proximal convoluted tubule. We've got Loop Diuretics

which act in the loop of henle and we've got sassy and spurring diuretics that tend

to ask me for it. Okay, so you can go back to this after I've gone through them

and identify where they all act of hopefully talk through the different mechanisms.

So clinical diuretics. There is something called Mannitol. There's an osmotic diuretic.

It has not occurred to have high osmotic ability. So Mannitol is a large polysaccharides

large sugar and it can be given to patients. If you need to reduce get rid of excess

fluid quite complete. It's quite good because it doesn't interact with any transport

proteins. It doesn't have an impact and if there are other medication it's not going

to interact with that.

Okay, so all it does is it's filtered?

It's filtered at the glomerulus. It enters the proximal convoluted tubule a bit

like glucose. It stays it gets filtered into the proximal convoluted tubule, but

unlike glucose. It doesn't get reabsorbed because there's no transport story.

It stays in the filtrate because it stays in the filtrate draws water because its

osmotically active into the filtrate. So therefore you lose more fluid.

Okay.

Doesn't act anything. So it's quite a nice inert directed to use if you want to

lose fluid quite quickly.

A second type that acts in the proximal convoluted tubule is carbonic anhydrase

Inhibitors. So we've all heard of Carbonic anhydrase. I mentioned it going to talked

about the proximal convoluted tubule. We've got Type 4 and type to remember the

membrane bound and the cytoplasmic helps to convert carbon dioxide and water to

carbonic acid which dissociates into protons and bicarbonate ions. Now bicarbonate

is reabsorbed with sodium.

So if we block the amount of sodium very brief inhibit the amount of bicarbonate

were producing for sort of inhibiting this transporter.

How about I can hydrolyze Inhibitors? Certainly acetazolamide is quite a mild diuretic

not tends to be used as directed very often. It's more commonly used in Ophthalmology

as a way of reducing intraocular pressure. So somebody's got glaucoma might've heard

of helps to reduce the pressure in the eye. It's quite mild. It's also been used

more recently the no one ever been walking in high altitude.

So there's a group called Diamox my third. Oh that's actually used to reduce altitude

induced alkalosis with the Philippines. And so that can be used. So that's also

the same drug here, but it can be used as a mild diuretic. Okay, and it works by

blocking duction of bicarbonate ions, and therefore reducing the amount of sodium

that's being reabsorbed that

Loop Diuretics, so I'm going to hear more about these next week. Loop diuretics

are really powerful. They're often used to treat hypertension or they can be use

to us in cerebral edema and other types of them were trying to you get rid of a

lot of fluid. These are little bit different. These are actually the enter the Lumen

into the filtrate by secretion. They actually use those organic and I am transporters.

So they're not filtered at the glomerulus. They're actually enter the field trip

proximal convoluted tubule tubular by secretion. They traveled to the loop of henle

where they block the sodium potassium to Chloride transporter. So by blocking that

they disrupt the counter-current multiplier and they're therefore stop the concentrating

ability. So you end up losing a lot of heard of my blocking the sodium potassium

to Chloride transporter. You lose a lot of fluids.

it

Terraces

and this egregious at buyouts are come back to this next Tuesday in part 2.

So we've narratives are really potent dramatic effects.

I said some reason to use their one of the problems with them though is because

you're blocking the sodium potassium to Chloride. You also block satin reabsorption,

which can cause hypokalemia. So anybody that's taking a look director usually has

to have a potassium supplement to maintain potassium levels and the other problem

with them is postural hypotension because they're quite dramatically

Cole's diuresis, then you lose a lot of fluid quite quickly and they can certainly

affect your blood pressure. So some people when they first start taking this binder

when they stand up they feel quite lightheaded because the blood pressure drops.

Sighs I diuretics or another class that can be used the example there is bendre

from the Fireside. So there's your hint remember this one tire sizes in the name

again, they can be filtered. It can also be scrutinized. So these both ways again,

they inhibit sodium reabsorption. They actually block the sodium chloride simple

these acts in the distal convoluted tubule rather the proximal convoluted tubule

and by blocking sodium chloride.

Blocking sodium less water. So again reasonably mild, but have quite useful effects

in treating hypertension high blood pressure.

So oops some of the problems with diuretics is if you don't take them, right you

can actually become quite dehydrated and that's one of the problems with people

taking them now come back to this end.

But it's taken at the wrong time or if you don't need them, you can actually cause

dehydration because they can cause hypokalemia they can be quite dangerous because

it can cause electrolyte imbalances.

Okay some others just to mention at the end here. So I hope you can see how these

fit in to all the diuretics which can be used are amiloride. So amiloride is a Blocker

of Enoch the epithelial sodium channel. So that blocks the sodium channels in the

collecting duct name is collecting duct. If we plot that we don't get aldosterone

increased water re-absorption.

We've also got spur on a lactone which is an antagonist of the aldosterone receptor.

So again these act in a similar way, but this one's acting at the aldosterone receptor.

This one's acting at the sodium channels that aldosterone stimulates, but both of

these will reduce sodium reabsorption in the collecting ducts and therefore prevent.

the good thing about these so if you don't have to talk to you about something really

important for balancing really important cardiac function and these tend to be used

in anybody that struggling with

Okay, so hopefully now you can test yourself by thinking of where all those different

types of directrix have their actions and you can talk to a little bit about the

mechanism of action good idea to have an example and how they work.

Okay, so we're on caution.

Okay, so

if somebody's on a diuretic such as furosemide, one of the problems is certainly

the older patients is that they don't like having to go to the toilet special you've

got mobility issues. If you are on a diuretic you not only need to go quite quickly

because you will be losing fluid through the renal system. But one of the problems

is you've got to maintain the water intake because if you don't if you decide which

can be seen with mud patients that they don't want to drink fluids don't want to

Target so they reduce the fluid intake.

If you're taking diuretics what that will do is it will still try and stimulate

you to urinate because you're still going to have blockage of for example Loop Diuretics,

so we would have to use two chloride transporter.

So you're going to producing you don't drink enough small amount of concentrated

urine.

That will then be picked up by the nephrons.

A condenser which will then stimulates and also your blood volume is going to drop

as long as you increase it will stimulate the renin-angiotensin system. So then

increase aldosterone secretion doing it more sodium being reabsorbed further down

the Nephron.

ADH would be stimulated. So you're going to try and reabsorb more fluid and what's

going to happen is you're going to get this concept of fluid rebound. So whereas

the drugs are there to try and meet you lose more fluid. If you don't drink enough

fluids with them, you can let your body's going to try and hold onto the fluid so

that you can actually counterproductive.

so I said

so it's really important to make sure that patients always continue drinking fluid

when they're taking these drugs.

Okay, we've almost forgotten that lives up to go and this was based on a real case

study. This was actually an individual that was living with an older relative on

the older relative was taking a loop diuretic and

the individual had

appreciated that all read that if you are dieting and want to lose weight one good

way to do. It salutes blew it because a lot of our body's fluid therefore one way

would be to reduce fluid intake or reduce the fluid in the body. So this person

was actually doing that and ended up abusing Loop diuretics.

So the actually started taking new directive. No didn't need them. The consequence

was to reduce blood pressure reduce blood volume became light-headed but because

of that they became hyperkalemic, which is actually quite

So they did have slight weight loss, but it didn't actually.