nf0368: okay so today you've got two lectures off me er the first one we're 
going to start and look at renal function and consider the concept of clearance 
as i've put it there the first bit's a bit of a reminder er to remind you what 
the composition of body fluids are you should know this this is A-level stuff 
if not degree then we're going to move on to how we regulate our body volume 
and then the last half of the lecture's looking at the kidney's function in 
terms of filtration clearance and i'm afraid the calculations that we can do er 
from these er parameters so if we look at an average man seventy kilograms and 
you can see a lot of hi-, a lot of us is water forty-two per cent roughly sorry 
sixty per cent forty-two litres is water that's a huge amount of water and we 
have to regulate that very carefully females we have slightly less the reason 
for that is as you on your sheet is er adipose tissue we have more and fat has 
less water in it so females actually less water 
proportionally than men and if you're very very lean you don't have as much at 
all and these are things to take into account obviously a very fat person 
compared to a very very thin person may have a slightly different water balance 
so this is just to remind you in an average situation here you are you've got a 
blood vessel a capillary you've got the endothelium through which things can 
move and then you've got the tissue that it butts up against and you've got all 
these different compartments of er fluid you've got interstitial you've got 
within the cells er you've got endothelial cells obviously have your and red 
blood cells in the plasma so if we then take those er different compartments 
and look at them er in more detail so again your average seventy kilogram man 
and you can see here intracellular fluid is sixty per cent and extracellular's 
forty so it's not quite fifty-fifty but it's of that sort of proportion and 
that's then further subdivided into these 
er proportions so the majority of your intracellular fluid comes from cells 
around the body but the red blood cells although they're in a fluid environment 
don't forget they're cells and have some water within them themselves and then 
your plasma and interstitial fluid splits er into these proportions now that's 
basically that should be er quick revision for you and don't get tied up in 
learning too many of those numbers just remember the basic principles it's 
roughly fifty-fifty er tissue to water in a human and roughly fifty-fifty 
extracellular to intracellular and then if we look at the composition of the 
fluids now this is where it becomes more important where the kidney has a 
greater role to play because obviously it regulates your ion concentration as 
well as your fluid and you can see here the osmolarity between the 
intracellular and extracellular is the same it should be the same and it's very 
important that they stay almost identical and we'll come to 
that in the next slide or two but if we look at the ionic composition between 
the er two er set-ups the ones coming in you'll need handouts that are at the 
back you can see here that they're composed of positive and negative ions and 
the important foin-, points are the ones that are in the biggest proportion so 
if you look here they're different between extracellular and intracellular here 
you've got sodium and chloride i think i've actually circled these for you er 
as your extracellular your main cation and main anion and in the intracellular 
it's potassium and phosphate so these are the four that are really important to 
remember which one's the important anion and cation intracellularly and 
extracellularly and if we move on to the next slide this is more important than 
anything and we come on to this i think it's about session six but don't hold 
me to that when we look at potassium balance potassium wants to be inside the 
cell sodium wants to be outside the cell 
and it's extremely important particularly that the potassium remains within the 
cell so if the only thing you remember from the last couple of slides is that 
potassium is inside and sodium's outside that'll be er okay and why i said the 
osmolarity was important between the extracellular and intracellular you all 
know about osmosis and if you don't go and remind yourself about osmosis but as 
you can see here if the osmolarities were not the same between the 
intracellular and extracellular fluid the cell is either going to swell or it's 
going to shrink either way you don't want that to happen in your body so you 
need to maintain the similar osmolarities that the cells maintain their normal 
structure represented by this pink blob here purple blob okay so that's a very 
quick refresher of things i hope you all know and if you don't know you're 
perfectly capable of just reading the handouts let's move on to fluid balance 
and obviously fluid balance is what the 
kidney's all about so here's your total body er water about forty-two litres 
and in a day this is what we should take in an average person food obviously is 
self-explanatory the water that comes from metabolism it's a breakdown product 
of lots of er metabolic reactions so you produce about four-hundred mls of 
water a day hopefully most of you are drinking about fifteen-hundred mls of 
water if you drink less than that you should up your intake and anything up to 
about two three litres is fine basically the more you drink as long you don't 
drink in excess the better for your kidneys so that's er something you should 
be advocating for your self and any of your patients as well but certainly 
fifteen-hundred would be a normal intake and most people would suggest a 
thousand to fifteen would be your absolute minimum so what do we excrete each 
day or get rid of you lose a lot through your lungs now if you haven't covered 
this on respiratory i'm sure you're going to 
but you breathe out a lot of water vapour during the day we sweat we lose some 
in faeces but you can see it's only a small amount fifteen-hund er a hundred 
millilitres and then you lose some in urine and this figure here is the only 
one that's variable obviously if you have something you go on a marathon you're 
going to sweat more than normal and if you drink er if you have diarrhoea 
you're going to lose more fluid er through your faeces than normal but if you 
don't do anything abnormal then within reason your lungs and your skin and what 
you lose through faeces these are relatively fixed volumes so the only way 
you've got to regulate your fluid volume is via your urine and if you actually 
do the sums if you add up these you'll see that the er five-hundred and the 
four-hundred there equates to this so basically your urine constitutes what you 
drink is what you get rid of in your urine as a very rough guide obviously 
there are variables now you have to 
actually pass four-hundred mls of urine day anything less than four-hundred mls 
and your kidneys begin to fail because they come into problems they're not 
passing enough fluid you're not actually getting rid of enough urine to be able 
to clear your body of all the metabolic waste products that you want to get rid 
of so you have to here as an absolute bare minimum is four-hundred so if people 
aren't taking in four-hundred mls of fluid and remember i've put drinking there 
but if it's a patient it may be an I-V drip if they're not getting four-hundred 
mls in then their kidneys are going to begin to suffer and you're going to have 
problems in terms of kidney failure and toxic build-up of waste so that's a 
really important er fact to remember so when we look at fluid balance obviously 
that's what we hope what you take in equals what you give out but it doesn't 
always happen so if you have if you're dehydrated it's hypovolaemia or hydr-, 
or fluid overload we call 
hypervolaemia and remember the kidney is the only organ that regulates your 
fluid so what are the symptoms these are in books they come up later when we 
look at blood pressure control so don't get too tied up with the symptoms and 
the causes and the treatments at this stage but basically they're fairly self-
explanatory if you're dehydrated or hypovolaemic you're usually thirsty your 
blood pressure will be low er because you have too little fluid volume 
circulating to maintain a normal blood volume so if you stand up you might be 
dizzy and confusion's a sign so they're quite nebulous and quite often happens 
in old people so you can see it's quite difficult old people do get confused 
and dizzy at the best of times so er it's always difficult to tease out the er 
specific symptoms but bear that in mind elderly people get dehydrated very 
quickly and signs that you might be looking for as a clinician er are things 
like i mentioned the blood pressure so they're going to 
have postural hypotension er they're going to have a low J-V-P weight loss if 
it's gone on for a while they begin to lose weight i mean everybody well a lot 
of the women will know one of the best ways to lose weight if you're anorexic 
or something is to take a diuretic and you'll lose a load of fluid quickly so 
you might see weight loss their mouth will be dry when you look in it and then 
they're going to have er very dry skin that's not elastic and obviously their 
urine output's going to be less than normal and conversely hypervolaemia is 
almost the opposite they get breathless because the lungs get congested with 
fluid and their ankles may swell from oedema now we don't actually cover oedema 
as a subject er but again it's something you should know about and they're 
going to have the opposite here basically so they may put on weight their blood 
pressure will go up so they'll be hypertensive and then er this goes to the 
fluid in the lungs you may be able to hear 
crackling in the lungs so that's the sort of things to look out for if you 
think somebody's got too much or too little fluid so how does the nephron 
control your fluid balance then so there's three main processes and these are 
the ones we're going to look at today you've got filtration we touched on this 
a little bit last week with glomerular structure but we're going to cover it a 
bit more today and the main aim of this is to sieve the plas-, the blood you 
want to sieve the blood so that you end up with er a protein-free plasma 
effectively all the plasma goes into the filtrate but not the proteins the 
nephron then has two very important functions one i-, is cun-, er secretion so 
it can secrete things into the er glomerular filtrate which will become urine 
so er has a role in P-H regulation and particularly here if you've got er 
foreign substances or drug metabolites you want to get rid of they may be 
secreted into the nephron and tubular reabsorption so we filter if you 
remember last week i was telling you that we filter the whole of our blood 
volume every five minutes and that accounts for a hundred-and-eighty litres a 
day now a hundred-and-eighty litres a day obviously we can't go on losing that 
amount of water you have to reabsorb it and most of what you filter through th-,
your kidneys is reabsorbed and that goes for everything on the whole unless 
it's a toxic substance you want to get rid of so everything so things like er 
most of the sodium you filter is reabsorbed you're only getting rid of half a 
per cent of the sodium that gets filtered in a day you get rid of more urea and 
that becomes important later in the course you reabsorb all your glucose you 
shouldn't have any glucose in your urine if you do that stri-, er will indicate 
diabetes mellitus and ninety-nine per cent of the water so you're only getting 
rid of er out of every hundred ml you filter you only pass one ml of urine and 
these two very much go together you'll see the 
secretion and reabsorption occur in similar regions of the nephron and 
sometimes they're actually linked together er not going to go into detail of 
those today because they come up in each separate bit of the module as we go 
along but it's important you remember that you filst-, have to filter it then 
you have the option of secreting or reabsorbing substances and those three 
things together are the crux of fluid er balance and the control of ions and 
electrolytes and then of course finally don't forget you got your urinary 
excretion and it's really important that you begin to get used to talking about 
secretion or excretion because the two are different depending on what you're 
talking about the excreted things are the things that in the urine that 
actually get removed from the body secreted things are items that go from the 
blood into the kidney er tubule so what exactly do i mean so here we have a 
schematic so this is your nephron that's your 
er Bowman's capsule and your glomerular tuft and here you've got and the artery 
goes in you've got your afferent arteriole efferent arteriole and it comes down 
into the peritubular network of blood vessels and you've got these three 
substances blue ones pink ones and green ones so they all come into the 
glomerular tuft together and then you'll find the blue and the green ones are 
filtered into the tubule so they're actually into the nephron lumen now but 
they don't behave the same then we actually want to keep the blue ones or keep 
the majority of the blue ones so you'll find they're actually reabsorbed back 
from the tubule into the circulation likewise the pink ones don't get filtered 
at all they go round they miss the er glomerular filtration er region into the 
peritubular circulation and then these get secreted into the nephron so the 
upshot of that in this very simplistic model is that the pink ones and the 
green ones get excreted whereas the blue ones are 
mostly if not completely reabsorbed into the blood system so that's the three 
main procedures so i said i'd talk about the glomerulus a bit more this week 
and how it actually does this filtration do you remember this picture from last 
week's lecture here's your capillary the endothelium with the capillary with er 
holes in it remember it's fenestrated then you've got the er basement membrane 
here and you got the epithelial cells which are the podocytes which are these 
specialized kidney cells and between them they allow things to move across now 
the filtration obviously occurs on the size and the shape because these holes 
are a physical barrier the fenestrations and the slits between the er podocytes 
so if you're too big you won't get across but the shape's important as well if 
you're flexible and can squash up as a molecule you may be theoretically too 
big but you may be able to squash up and fit through one of these slits or 
holes and the charge is important the 
podocytes and the basement membrane are negative and proteins tend to be 
negative so that will stop help to stop proteins crossing across the glomerular 
er membranes because the negatives will repel each other having said that it's 
the podocytes that form the really restrictive layer the fenestrations here are 
bigger than the slits between the podocytes so this is a rough guide as to 
what's going to happen now these numbers will alter as i've just said depending 
on the shape and the charge of the er molecule that wants to be filtered or not 
but roughly anything less than seven kilodaltons is going to come across with 
no barriers whatsoever then you've got a grey area up to seventy kilodaltons 
where generally it's permeable to those and molecules less than that size in 
weight will generally get across and anything above seventy usually won't and 
that includes all the proteins so most proteins are above seventy or if they're 
not they have the negative charge which 
will encourage them not to come across but the filtration actually depends on 
pressure because th-, it's acting like a sieve if you imagine now the 
glomerular structure's like a sieve with the holes in but you need the pressure 
to force things across and we're going to look at that er exactly how that 
works in the next couple of slides but in order to help it it's got two things 
one the capillary walls are a hundred times more permeable than other 
capillaries throughout the body and as we'll see later they've got a greater 
pressure the er er the pressure of blood within the arterioles in the 
glomerular tuft is greater so they're more permeable and the blood is at a 
higher pressure and those two factors together force the fluid through the 
glomerulus and into the kidney er nephron so okay so this is er a recap of what 
i've said basically you've got pressure from the artery and you've got this 
movement of fluid now there's two other things to take account of here 
it's not a simple pressure thing remember you have fluid in the glomerulus and 
you have fluid within the Bowman's capsule and the kidney nephron and the both 
of those will exert an hydrostatic pressure so the the fluid that is already 
within the nephron will push in one direction the fluid that's within the 
capillaries will push in another direction or the interstitial fluid will push 
in another direction you have blood pressure to take account of and you also 
have these er oncotic pressures now you should have covered these and er 
Starling's forces in lots of detail i believe in the cardiac cardiovascular 
module which was last semester er but if you can't remember just remind 
yourself briefly of what they are but this is due to proteins proteins 
themselves er will cause fluid to want to move from one place to another and 
that's known as oncotic the pressure due to the protein er is oncotic pressure 
so if we move this into a glomerulus and see what that actually looks 
like here as you can see this is your glomerular going with your blood flow 
coming in and out so you've got your blood pressure represented here by these 
er numbers so you've got your blood pressure into your er kidney tubule you 
have the hydrostatic pressure exerted here by the fluid that's already in the 
tubule pushing back and then you've got the oncotic pressure from the plasma 
proteins er there are lots of proteins in here and there are no proteins unless 
something's wrong in here so if we move on to the there is a calculation here 
i've put it down for you don't worry you won't be asked to exaplain that or 
write it down but remember that you've got blood pressure one way hydrostatic 
pressure the other way and oncotic pressure the other way and the oncotic 
pressure works like this in the tubule you have very little protein two to five 
nanograms per ml but in the plasma you've got six to eight grams so that's a 
huge huge th-, er variation in the amount of 
protein and what that means is that the water in order to equal out the protein 
concentrations the water tries to move from the kidney tubule into the plasma 
and that will exert a pressure because obviously it doesn't go back that way 
naturally so when you put these together you actually find if you add these 
sums up you can see the numbers are there you've only got a ten millime-, er 
millimetres of mercury pressure forcing stuff into the tubule that's not very 
much that's quite a low pressure but remember i said that the capillaries are 
more permeable than normal and remember the glomerular structure's like a ball 
of wool so you've got an awful lot of capillaries within the glomerulus that er 
large surface area actually causes you to be able to filter a lot of er blood 
within a small space of time as i've already said it's a hundred-and-eighty 
litres a day okay so we come on to the glomerular filtration rate and that's 
the rate that you are able to filter blood and 
produce a glomerular filtrate quite reasonably self-explanatory now in a male 
it's about a hundred-and-fifty mls per minute and you see i've written it up 
here it's a hundred-and-fifty mls per minute and that's the surface area of a 
man an average man now most people will talk about er G-F-Rs as just like mls 
per minute most of the nephrologists will most normal clinicians will but it's 
important to remember its correct units have a surface area attached to them 
and this becomes im-, particularly important when you look at neonates and old 
people because obviously their surface area if you're very small are very sma-, 
er sm-, small old frail lady or small baby becomes important so you need to 
remember it's per surface area and you will lose marks if i ask for a G-F-R and 
you give me mls per minute and not mls per minute per surface area so it's if 
you can't remember it's one-point-seven-three an average man you it's all right 
if you put per surface area 
i'll let you off on that one but it is important to remember that's its correct 
units and again it's a bit less in females and it decreases with age as you get 
older okay now your G-F-R actually remains constant your blood pressure goes up 
and down dur-, out the day goes up and down depending on what you're doing but 
your G-F-R tries to remain as constant as possible and it does this be-, by 
dilating the arteries if you remember you have an arteriole in and out and 
there are ways of controlling er both the efferent and the afferent arterioles 
and that's how it regulates blood pressure or or adapts to blood pressure 
rather so if we have a look here if your blood pressure increased you've got 
more pressure in the glomerular tuft in theory which would force more fluid 
through er into the tubules and increase your G-F-R that would be what you 
would expect to happen but it doesn't happen because this is what happens here 
this is a normal 
glomerulus say you've got in and out arterioles at roughly equal er sizes and 
that's your normal blood flow and normal pressure if your blood pressure goes 
up a series of mechanisms come into play which actually constrict the afferent 
arteriole which restricts the amount of blood that flows into the glomerular 
tuft if you restrict the blood that effectively compensates for the increased 
blood pressure and so you maintain the amount of force that's provided by the 
blood er as the same likewise it works in reverse if your B-P drops you would 
expect if there's less pressure your g-, er G-F-R's going to drop now that's 
seriously we don't want that to happen because there are reas-, times when your 
blood pressure drops and you don't want your kidneys to stop working because if 
your G-F-R drops to almost nothing and you stop making urine your kidneys fail 
quite quickly and although it might not be er a failure forever it's a serious 
medical condition so the body doesn't 
want that to happen so it wants to keep the pressure within the glomerulus high 
so that filtration goes on as normal so it does the opposite there and this 
time it dilates the afferent arteriole and er you get far more blood flow going 
through into the glomerulus and that compensates for the change in pressure 
keeps the pressure up and the G-F-R stays the same so generally throughout the 
day whatever happens to our blood pressure our G-F-R's going to be constant er 
that's what i said er this is just to remind you this isn't anything i expect 
you to know yet some of these things will come up as we go through the module 
but there are drugs that regulate er blood pressure or er arteriole 
constriction or dilatation don't worry about what they are yet they're listed 
here simply 'cause i took it out of a book some of these will be pointed out to 
you as the course goes through but if certain drugs alter your arteriole 
pressure in your glomerulus either by constricting or dilating 
the efferent or the ef-, afferent arterioles that will affect G-F-R and may 
affect kidney function so you just need to bear that in mind so what happens if 
you've got clinical conditions your G-F-R stays constant normally but obviously 
there's times when that doesn't work so if you have an obstruction somewhere 
within the er urinary system that causes the pressure of the fluid within the 
tubule to build up the hydrostatic pressure then backs up and causes a greater 
force of pressure from within the tubule out through the glomerulus preventing 
filtration occurring so in that case your G-F-R will drop so somebody who has a 
blockage a build-up of fluid will their G-F-R drops again obviously changes in 
the glomerulus are an important er factor to bear in mind so if your glomerulus 
blocks up effectively your G-F-R will drop your urine output will drop and er 
you have kidney problems but likewise if there's damage that causes it to leak 
then y-, er 
fluid's going to flood through your glomerulus and you're going to have an 
increased G-F-R and an increased urine output now those are usually reasonably 
obvious to spot either because something's in the urine that shouldn't be there 
because it's got across the glomerulus or your urine output goes up or down 
accordingly er and then you have to start to investigate why but i just want to 
put down here that a very small change in kidney function they're they're 
hugely adaptive we're only using a small percentage of their er ability er you 
know 'cause er people with only one kidney either because they've lost one 
through illness or er they've had a transplant you only get one when you have a 
transplant they function perfectly well they don't have to restrict their diet 
or anything particularly to compensate for having lost half of their renal 
function effectively but a small change can have a problem or or can er 
manifest itself as something obvious so here we've got two 
G-F-Rs the same and you would normally produce one ml of er urine per minute 
that's what's our normal production but you can see if you start producing two 
mls of urine per minute that's actually a small amount here so you're only 
altering your reabsorption by one ml and your excretion by one ml but that's 
actually doubling your urine output so although per minute that doesn't seem 
much you take that into account over a day that's a huge volume change 
nf0368: so moving on now to renal clearance and that's simply the ability of 
your kidneys to clear whatever you're talking about from the blood and it's an 
actual quantity and again it's got units it's per ml of plasma per time and 
you'll see why in a minute and it's completely independent of the amount of 
urine you produce so if you clear ten milligrams of something per minute it's 
going to be ten milligrams per minute whether you're peeing one litre in an 
hour or two litres in an hour obviously it's more dilute in the urine 
but what you clear from the blood stays the same is that clear so the urine 
concentration has nothing to do with your renal clearance that's a b-, er that 
relates to the amount you clear from the plasma or the blood now obviously 
there are times when we want to calculate how effectively the kidneys are 
working the times when we want to know what the glomerular filtration rate is 
there are times when we want to know what the renal blood flow er is and we can 
calculate that as well and we'll come on to that towards the end but the G-F-
R's a really useful one to calculate if you have glomerular diseases you're 
going to notice a change in the G-F-R so it's something that clinicians do 
regularly so in order to calculate that if something is cleared er from the 
blood by filtration alone then the rate that it's its renal clearance equals 
the glomerular filtration rate so if it's c-, er purely filtered the rate at 
which it's filtered is the rate it's cleared from the 
blood okay so how do we calculate this and one thing i've put up here it's 
important to remember that this is comes in remember i said remember to get 
excretion and secretion the right way round also remember to start getting in 
the habit of using urine and filtrate in the right er context urine is only 
urine [laughter] urine is only urine once the filtrate enters the collecting 
system until it enters the collecting tubules anything before that is 
technically known as filtrate er so when i'm talking about stuff that's within 
the glomerular neph-, er the nephrons rather that's always filtrate until it 
enters the collecting system so if something is purely filtered not reabsorbed 
into the bloodstream the concentration in the filtrate is exactly the same as 
the concentration in the plasma so in order to measure it we need something 
that's freely filtered you don't want any kind of barrier to its filtration 
across the glomerulus we don't want anything that's er absorbed or 
secreted and we don't want it to be made or metabolized by the kidneys and 
that's actually quite a limiting er selection of finding things to do like that 
so we have inulin which is the ideal it's the gold standard if you really 
really have to know very accurately the G-F-R you have to use inulin but it's 
infused and it's not easy to measure in a lab so it's not an ideal it's not an 
easy test to do but creatinine is easy that's a br-, a natural breakdown 
subject er sub-, er substance we've got here it's freely filtered it's not 
reabsorbed so that fulfills all the criterias we do have a little bit of 
secretion of it that's not a huge problem and i'll explain why on the next 
couple of slides but you have to bear that in mind we do secrete a small amount 
of creatinine so it's not an ideal substance but it's the best we've got so how 
do you calculate it so i'm sorry you've got all these calculations but i've 
written them all out for you and if you have any trouble catch me in 
the group work afterwards but i'll take you through them now so here are our G-
F-R you know i've put mls per minute i haven't bothered with the surface area 
there 'cause the calculation's easier er to explain that way this is the volume 
of er urine so you have to measure how much urine you're producing over a 
certain time and work out the rate per minute this is the creatinine 
concentration in the urine so just want that as a concentration and this is the 
plasma concentration so you want to compare how much is in the urine to how 
much is in the plasma basically and that will give you the rate at which it's 
being filtered and you can see the units cal-, these units c-, er cancel out so 
you're left with mls per minute and that er calculation here this i've got down 
to determine G-F-R but you can replace that with renal clearance this 
calculatio-, or this equation will calculate the renal clearance of anything 
you can look at how much is in the urine versus how much is in the 
blood now or plasma we're using this for creatinine so that equates to G-F-R 
but if it was a different substance that wasn't completely cleared then it 
would be the renal clearance number so just r-, bear that in mind so is it a 
good estimate remember i said that some of it was secreted as well it's not a 
big problem the assay that measures er plasma creatinine overestimates so the 
two of them cancel each other out the bit of secretion that comes from the body 
versus the overestimation of the plasma creatinine tend to cancel each other 
out er so it's not a huge problem however it can become a problem when you have 
a er an illness so if the er if the G-F-R drops you get more secreted by the 
kidneys to try and keep the blood level equal the idea is er you have the 
ability to secrete so that if for some reason your filtration isn't working 
very well you don't want the creatinine to build up in your blood so the the 
body says oh that's doesn't matter if it's 
not being filtered that's fine i'll send it a bit further round the er tubular 
capillary network and secrete it directly into the tubules obviously if your 
secretion goes up then when i said that secretion and overestimation of plasma 
cancel each other out that doesn't occur any more so if you have somebody that 
you know has glomerular filtration problems then creatinine is not a good 
estimate of G-F-R the other problem i haven't actually er got the graph with me 
here but it's in nearly every textbook in order for you to see a change er in 
plasma creatinine levels because of this ability to secrete your G-F-R has to 
drop by about fifty per cent so if you're simply measure-, er plasma creatinine 
and you'll find this comes back week after week in the group work you get urea 
and electrolytes and creatinine the creatinines will go up eventually but 
because of your ability se-, to secrete it they will only go up when you've 
lost half of your G-F-R capacity or 
theresabouts so if you simply look at plasma creatinine levels er they could be 
masking an underlying kidney condition so you just have to bear because the 
creatinine's normal it doesn't necessarily rule out some problem with the er 
kidneys although it is used routinely but that does mean the moment you see the 
plasma creatinine to go up you know you've got a real problem with your kidneys 
this is another thing to bear in mind it depends on muscle mass it's a 
breakdown of muscle mass little old ladies Asian people they have a completely 
different muscle mass from the average white person and you have to bear that 
in mind their creatinines may be different as a consequence ah i've said that 
already i'm not going to discuss this now this table looks at er whether 
something is filtered or reabsorbed or secreted or a combination of which and 
gives you er examples here tells you what happens to the substance examples 
here and then what you would see in the renal vein 
versus the renal artery is the concentration going to be higher or lower or the 
same and ha-, what sort of renal clearance you would expect in comparison to a 
G-F-R now what i want you to do is have a look at this and make certain for 
each of those you can work out why when i said this one isn't filtered er it's 
going to be the same in the artery versus the brain and er [laugh] artery 
versus the vein rather and have no renal clearance and do that for all of them 
if you can't work out why that table's as it is just come and see me in the 
group work i'm kind of floating around in the group work and we'll go through 
it 'cause it is important that you understand er secretion absorption and 
filtration and excretion and i'll happily excuse me i'll happily go over that 
later on this morning so i said i wanted to calculate renal blood flow 
occasionally and this is the rate at which the blood flows through the kidneys 
pretty obvious how much goes in versus how much comes 
out now in order to do this we actually use er a function of the kidneys when 
the blood flows into the glomerulus not all of it is filtered obviously you 
have a flatbed of er er endothelium basement membrane and epithelium and you 
have blood flow over the top now not all of that blood flowing over the top is 
going to be in contact with the capillaries and is going to be able to be 
filtered through the the blood in the centre of the capilla-, of the arteriole 
is basically going to go whizzing past over the top of the meshwork of er 
sieving apparatus so only the a proportion of the blood is actually filtered at 
any one time and i'll show you on almost the last slide what it is but roughly 
that works out to eighty per cent goes whizzing straight past into the 
peritubular circulation and twenty per cent is filtered into the er nephron and 
that's known as the filtration fraction now we can use this the consequences 
are if you look at e-, urea fifty per cent er of urea 
well the urea's filtered but then some of it is reabsorbed so you can see that 
some goes through the kidneys and some er is reabsorbed but as it's not 
secreted back into the kidneys only the proportion that actually gets filtered 
can ever get cleared in one time so the only way you have of clearing urea is 
to filter it though the glomerulus so if only twenty per cent of your blood is 
going into the glomeru-, through the glomerulus into the tubule network you 
need five passes of blood to clear it of uri-, urea effectively okay however 
some substances if they're filtered and secreted or just completely secreted on 
their own you only need a single pass so if the substance is filtered through 
the glomerulus into the tubule network twenty per cent of it will get filtered 
the other eighty per cent of it goes round into the peritubular circulation 
that eighty per cent that's escaped the first pass into the peritubular 
circulation will then be secreted directly into 
the tubules so the whole hundred per cent of that particular substance gets 
into the nephron in one go of the blood through the nephron circulation does 
that make sense okay and we can use that to work out the renal blood flow and 
one substance that does this is P-A-H okay so here we have green blobs going 
into the glomerulus some gets filtered some goes into the circulation but as it 
comes into the circulation when it gets to the correct part of the nephron it's 
secreted into the tubule the consequences are you have P-A-H coming in P-A-H 
going out in urine but hardly any at all in the renal vein and we use this so 
we calculate in this case renal clearance which was i told you just the amount 
that's er filtered effectively equals the G-F-R of P-A-H plus the amount 
secreted and equals what we call the renal plasma flow so you calculate the 
renal clearance of P-A-H exactly the same way as we used creatinine to 
calculate G-F-R so if you want to work out the calculation here 
you've got the volume of urine the urine concentration of P-A-H the plasma 
concentration of P-A-H and that gives you the renal clearance of P-A-H which 
equals the renal plasma flow okay however you want to work out the blood flow 
blood flow's not just plasma it's got red blood cells so you need to know what 
the haematocrit is 
nf0368: we've calculated the er er clearance rate from the plasma to con-, er 
to turn that into blood you need to just allow for the er number of red blood 
cells so if you do a haematocrit if you find that say forty-five per cent's red 
blood cells er and fifty-five per cent is plasma the renal clearance of P-A-H 
is fifty-five per cent of what the er renal blood flow is so all you simply do 
to your simple calculation is you take your er renal clearance of P-A-H which 
is about six-hundred mls per minute and you multiply that you just do 
correction factor to allow for fifty-five per cent so in this case using those 
numbers your renal blood flow is just over a litre per 
minute okay you're not going to be used asked to calculate all of these in 
exams or anything so don't worry so remember i said we use the filtration 
fraction the fact that only twenty per cent of the er blood gets filtered at 
only one time you can backtrack that i told you it was twenty per cent but you 
can actually calculate it as well so if you take your glomerular filtration 
rate and compare that with your renal plasma flow that will tell you how much 
of the blood was filtered the first time round so if we put our numbers in 
that's your standard G-F-R i've just told you the renal clearance for P-A-H is 
six-hundred and if you do that calculation it comes out to twenty-point-eight a 
little bit more but er so that's very simple so you can actually work out the 
fractions and sometimes these sort of inf-, these numbers are useful if you're 
trying to work out what your glomerular function actually is okay we've said 
that so if we look at secretion and 
absorption now now this is what i was saying last wi-, week you have to remind 
yourself of active passive transport er simple diffusion cotransporters et 
cetera er they are all going to crop up in the later sessions of this module er 
but this is just to remind you that basically things go through cells or 
between them and they might need energy and they might not but the one thing 
you have to remember in the kidney is that it's arranged like this so here you 
have this is the nephron with the er filtrate in it and cells either side 
[cough] excuse me this is your capillary er and obviously that is semipermeable 
and you have your interstitial fluid now things may go between the cells in 
either direction and just diffuse simply between the cells that's quite simple 
however if an active transport is needed you need to have some mechanism to get 
it into your tubular cell and you need another transport mechanism to get it 
out and then obviously 
it can simply diffuse into the blood if that's where it's going but it's really 
important to remember when we're talking about whether things are secreted or 
reabsorbed in the kidney they have to go from the either from the er lumen of 
the nephron the filtrate into a tubular cell across the cell and out the other 
side so you have transport mechanisms on both sides and likewise if they're 
going into the tubule er lumen you have again out of the blood into 
interstitial fluid and then you've got two membranes it has to get across and 
you have to remember that so okay so these are the things i want you to go home 
with and hopefully remembered we've got these four processes occurring and 
remember as mentioned get your secretion and excretion right i mean it's 
difficult to say i mean even i'm not foolproof i you'll find i 
sometimes talk about the wrong one or i talk about urine when i mean filtrate i 
mean i-, it does happen and again just remember whether you're talking about 
filtrate or urine and then these are the things that we can calculate G-F-R is 
the number that you're most often going to come across but using the er 
mechanisms of calculating the G-F-R you can calculate these other things as 
well and then next week we're going to talk about er blood pressure control in 
more detail and look at sodium mechan-, well i'm not talking about it next week 
er somebody from namex is but we'll pick up and take it further down and look 
at the regulation of sodium so i've overrun a little bit er we need to just 
move on reasonably swiftly to the next one so that namex can come in er but i 
just have to sort this out a minute so you've got a couple of minutes while i 
swap files over on here