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<title>Introduction to Renal Function: The Concept of Clearance</title></titleStmt>

<publicationStmt><distributor>BASE and Oxford Text Archive</distributor>


<availability><p>The British Academic Spoken English (BASE) corpus was developed at the

Universities of Warwick and Reading, under the directorship of Hilary Nesi

(Centre for English Language Teacher Education, Warwick) and Paul Thompson

(Department of Applied Linguistics, Reading), with funding from BALEAP,

EURALEX, the British Academy and the Arts and Humanities Research Board. The

original recordings are held at the Universities of Warwick and Reading, and

at the Oxford Text Archive and may be consulted by bona fide researchers

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only; they should not be reproduced in teaching materials</p>

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<p>4. The corpus developers should be informed of all presentations or

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Researchers should acknowledge their use of the corpus using the following

form of words:

The recordings and transcriptions used in this study come from the British

Academic Spoken English (BASE) corpus, which was developed at the

Universities of Warwick and Reading under the directorship of Hilary Nesi

(Warwick) and Paul Thompson (Reading). Corpus development was assisted by

funding from the Universities of Warwick and Reading, BALEAP, EURALEX, the

British Academy and the Arts and Humanities Research Board. </p></availability>




<recording dur="00:43:05" n="7830">


<respStmt><name>BASE team</name>



<langUsage><language id="en">English</language>



<person id="nf0368" role="main speaker" n="n" sex="f"><p>nf0368, main speaker, non-student, female</p></person>

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<personGrp id="sl" role="all" size="l"><p>sl, all, large group</p></personGrp>

<personGrp role="speakers" size="3"><p>number of speakers: 3</p></personGrp>





<item n="speechevent">Lecture</item>

<item n="acaddept">Medicine</item>

<item n="acaddiv">ls</item>

<item n="partlevel">UG2/PG</item>

<item n="module">Urinary System</item>




<u who="nf0368"><kinesic desc="projector is on showing slide" iterated="n"/> okay so today you've got two lectures off me <pause dur="0.8"/> # the first one we're going to start and look at renal function <pause dur="0.6"/> and consider the concept of clearance as i've put it there <pause dur="0.4"/><kinesic desc="changes slide" iterated="n"/> the first bit's a bit of a reminder <pause dur="0.2"/> # to <pause dur="0.5"/> remind you what the composition of body fluids <pause dur="0.3"/> are you should know this this is A-level stuff if not degree <pause dur="0.9"/> then we're going to move on to how we regulate our body volume <pause dur="0.5"/> and then <pause dur="0.2"/> the last half of the lecture's looking at the kidney's function in terms of filtration <pause dur="0.5"/> clearance and i'm afraid the calculations that we can do <pause dur="0.4"/> # <pause dur="0.3"/> from these # <pause dur="0.2"/> parameters <pause dur="1.3"/><kinesic desc="changes slide" iterated="n"/> so if we look at an average man <pause dur="0.2"/> seventy kilograms <pause dur="0.4"/> and you can see <pause dur="0.4"/> a lot of <trunc>hi</trunc> a lot of us is water forty-two per cent roughly <pause dur="0.5"/> sorry sixty per cent forty-two litres <pause dur="0.3"/> is water that's a huge amount of water <pause dur="0.4"/> and we have to regulate that very carefully <pause dur="1.1"/> females we have slightly less <pause dur="0.9"/> the reason for that is as you on your sheet is <pause dur="0.2"/> # adipose tissue <pause dur="0.6"/> we have more <pause dur="0.3"/> and fat has less water in it so females actually less water <pause dur="0.4"/>

proportionally than men <pause dur="0.9"/> and if you're very very lean you don't have as much at all <pause dur="0.4"/> and these are things to take into account obviously a very fat person <pause dur="0.3"/> compared to a very very thin person may have a slightly different water balance <pause dur="1.1"/><kinesic desc="changes slide" iterated="n"/> so this is just to remind you <pause dur="0.3"/> in an average situation here you are you've got a blood vessel a capillary <pause dur="0.9"/> you've got the endothelium through which things can move <pause dur="0.4"/> and then you've got the tissue that it butts up against <pause dur="0.5"/> and you've got all these different compartments of # fluid you've got interstitial <pause dur="0.3"/> you've got within the cells <pause dur="0.3"/> # <pause dur="0.3"/> you've got endothelial cells obviously have your <unclear>and</unclear> red blood cells in the plasma <pause dur="1.1"/><kinesic desc="changes slide" iterated="n"/> so if we then take those # different compartments <pause dur="0.3"/> and look at them # <pause dur="0.8"/> in more detail <pause dur="0.7"/> so again your average seventy kilogram man <pause dur="0.6"/> 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 <pause dur="0.7"/> and that's then further subdivided <pause dur="0.3"/> into these

# proportions so <pause dur="0.3"/> the majority of your intracellular fluid comes from cells around the body <pause dur="0.4"/> but the red blood cells although they're in a fluid environment don't forget they're cells and have some water <pause dur="0.4"/> within them themselves <pause dur="0.4"/> and then your plasma and interstitial fluid splits <pause dur="0.5"/> # <pause dur="0.3"/> into these proportions <pause dur="1.4"/> now that's basically that should be # quick revision for you <pause dur="0.3"/> and don't get tied up in learning too many of those numbers just remember the basic principles it's <pause dur="0.3"/> roughly fifty-fifty <pause dur="0.5"/> # <pause dur="0.7"/> tissue to water in a human and roughly fifty-fifty extracellular to intracellular <pause dur="1.3"/><kinesic desc="changes slide" iterated="n"/> 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 <pause dur="0.3"/> it regulates your ion concentration as well as your fluid <pause dur="0.6"/> and you can see here the osmolarity <pause dur="0.4"/> between the intracellular and extracellular <pause dur="0.3"/> is the same <pause dur="0.4"/> it should be the same and it's very important that they stay almost identical <pause dur="0.7"/> and we'll come to

that in the next slide or two <pause dur="1.0"/> but if we look at the <pause dur="0.3"/> ionic composition between the # <pause dur="0.2"/> two <pause dur="0.6"/> # set-ups <event desc="students enter room" iterated="n" n="ss"/> the ones coming in you'll need handouts that are at the back <pause dur="1.4"/> you can see here <pause dur="0.3"/> that they're composed of positive and negative ions <pause dur="0.4"/> and the important <trunc>foin</trunc> <pause dur="0.3"/> points are <pause dur="0.4"/> the ones that are in the biggest proportion so if you look here they're different between extracellular and intracellular <pause dur="0.5"/> here you've got sodium and chloride <pause dur="0.7"/> i think i've actually circled these for you <pause dur="0.5"/> # as your extracellular your main cation and main anion <pause dur="0.5"/> and in the intracellular it's potassium and phosphate <pause dur="0.8"/> so these are the four that are really important to remember which one's the important anion and cation <pause dur="0.3"/> intracellularly <pause dur="0.2"/> and extracellularly <pause dur="0.8"/><kinesic desc="changes slide" iterated="n"/> and if we move on to the next slide <pause dur="0.4"/> 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 <pause dur="0.4"/> when we look at potassium balance <pause dur="0.5"/> potassium <pause dur="0.2"/> wants to be inside the cell <pause dur="0.4"/> sodium wants to be outside the cell <pause dur="0.2"/>

and it's extremely important particularly that the potassium remains within the cell <pause dur="0.4"/> so if the only thing you remember from the last couple of slides is that potassium is inside <pause dur="0.3"/> and sodium's outside <pause dur="0.4"/> that'll be <pause dur="0.4"/> # okay <pause dur="2.1"/><kinesic desc="changes slide" iterated="n"/> and why i said the <pause dur="0.3"/> osmolarity was important between the extracellular and intracellular <pause dur="0.3"/> you all know about osmosis and if you <shift feature="voice" new="laugh"/>don't go and remind <shift feature="voice" new="normal"/>yourself about osmosis <pause dur="0.5"/> but as you can see here <pause dur="0.4"/> if the osmolarities were not the same between the intracellular and extracellular fluid <pause dur="0.3"/> the cell is either going to swell <pause dur="0.3"/> or it's going to shrink <pause dur="0.3"/> 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 <pause dur="0.4"/> represented by this pink blob here <pause dur="0.2"/> purple blob <pause dur="1.5"/> 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 <pause dur="0.9"/><kinesic desc="changes slide" iterated="n"/> let's move on to fluid balance <pause dur="1.2"/> and obviously fluid balance is what the

kidney's all about <pause dur="0.7"/> so here's your total body <pause dur="0.2"/> # water <pause dur="0.3"/> about forty-two litres <pause dur="0.9"/> and in a day this is what we should take in an average person <pause dur="0.8"/> food <pause dur="0.4"/> obviously is <pause dur="0.2"/> self-explanatory the water that comes from metabolism it's a breakdown product of lots of # metabolic reactions so you produce about four-hundred mls of water a day <pause dur="0.7"/> hopefully <pause dur="0.3"/> most of you are drinking about fifteen-hundred mls of water <pause dur="0.4"/> if you drink less than that you should up your intake and anything up to about <pause dur="0.4"/> two three litres is fine <pause dur="0.2"/> basically the more you drink as long you don't drink in excess the better for your kidneys so <pause dur="0.5"/> that's # <pause dur="0.4"/> something you should be advocating for your self and any of your patients as well but certainly fifteen-hundred <pause dur="0.3"/> would be a normal intake and <pause dur="0.2"/> most people would suggest a thousand to fifteen would be your absolute minimum <pause dur="1.3"/> so what do we excrete each day or get rid of <pause dur="0.5"/> 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 <pause dur="0.6"/> we sweat <pause dur="0.5"/> we lose some in faeces but you can see it's only a small amount <trunc>fifteen-hund</trunc> # a hundred millilitres <pause dur="0.5"/> and then you lose some in urine <pause dur="0.8"/> and this figure here <pause dur="0.3"/><kinesic desc="indicates point on slide" iterated="n"/> is the only one that's variable <pause dur="0.7"/> obviously <pause dur="0.4"/> if you have something you go on a marathon you're going to sweat more than normal <pause dur="0.6"/> and if you drink # if you have diarrhoea you're going to lose more fluid # through your faeces than normal <pause dur="0.5"/> but if you don't do anything abnormal <pause dur="0.4"/> then within reason your lungs and your skin and what you lose through faeces <pause dur="0.3"/> these are relatively fixed volumes <pause dur="0.5"/> so the only way you've got to regulate your fluid volume <pause dur="0.3"/> is via your urine <pause dur="0.5"/> and if you actually do the sums if you add up these <kinesic desc="indicates point on slide" iterated="n"/> <pause dur="0.3"/> you'll see that <pause dur="0.2"/> the # five-hundred and the <pause dur="0.2"/> four-hundred there equates to this <pause dur="0.4"/> so basically <pause dur="0.3"/> your urine constitutes <pause dur="0.2"/> what you drink <pause dur="0.3"/> is what you get rid of in your urine <pause dur="0.2"/> as a very rough guide <pause dur="0.2"/> obviously <pause dur="0.2"/> there are variables <pause dur="1.8"/> now <pause dur="0.5"/> you have to

actually <pause dur="0.2"/> pass four-hundred mls of urine day <pause dur="0.4"/> anything less than four-hundred mls <pause dur="0.4"/> and your kidneys begin to fail because they come into problems <pause dur="0.3"/> they're not passing enough fluid <pause dur="0.3"/> 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 <pause dur="0.6"/> so <pause dur="0.5"/> you have to <kinesic desc="indicates point on slide" iterated="n"/> here as an absolute bare minimum is four-hundred <pause dur="0.6"/> so if people aren't taking in four-hundred mls of fluid and remember i've put drinking there <pause dur="0.3"/> but if it's a patient it may be an I-V drip <pause dur="0.5"/> if they're not getting four-hundred mls in <pause dur="0.6"/> then their kidneys are going to begin to suffer <pause dur="0.3"/> and you're going to have problems in terms of kidney failure and toxic build-up of waste <pause dur="0.4"/> so that's a really important # fact to remember <pause dur="1.6"/><kinesic desc="changes slide" iterated="n"/> so when we look at fluid balance <pause dur="0.2"/> obviously that's what we hope <pause dur="0.3"/> what you take in equals what you give out <pause dur="0.6"/> but it doesn't always happen <pause dur="0.7"/> so if you have <pause dur="0.3"/> if you're dehydrated it's hypovolaemia <pause dur="0.7"/> or <trunc>hydr</trunc> or fluid overload we call

hypervolaemia <pause dur="0.9"/> and remember the kidney is the only organ that regulates your fluid <pause dur="1.7"/><kinesic desc="changes slide" iterated="n"/> so what are the symptoms <pause dur="0.6"/> 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 <pause dur="0.6"/> but basically they're fairly self-explanatory <pause dur="0.6"/> if you're dehydrated or hypovolaemic <pause dur="0.4"/> you're usually thirsty <pause dur="0.8"/> your blood pressure will be low <pause dur="0.4"/> # <pause dur="0.5"/> because <pause dur="0.3"/> you have too little fluid volume circulating to maintain a normal blood volume <pause dur="0.4"/> so if you stand up you might be dizzy <pause dur="0.5"/> and confusion's a sign so they're quite nebulous <pause dur="0.5"/> and <pause dur="0.4"/> 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 <pause dur="0.4"/> # it's always difficult to tease out the # specific symptoms <pause dur="0.3"/> but bear that in mind elderly people <pause dur="0.4"/> get dehydrated very quickly <pause dur="1.1"/> and signs that you might be looking for as a clinician <pause dur="0.4"/> # <pause dur="0.5"/> are things like i mentioned the blood pressure so they're going to

have postural hypotension <pause dur="0.5"/> # they're going to have a low J-V-P <pause dur="0.5"/> weight loss <pause dur="0.3"/> if it's gone on for a while they begin to lose weight i mean everybody well <pause dur="0.3"/> 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 <pause dur="0.4"/> so you might see weight loss <pause dur="0.4"/> their mouth will be dry when you look in it <pause dur="0.5"/> and then they're going to have # <pause dur="0.2"/> very dry skin that's not elastic <pause dur="0.3"/> and obviously their urine output's going to be less than normal <pause dur="0.7"/> and conversely hypervolaemia is almost the opposite <pause dur="0.5"/> they get breathless because the lungs get congested with fluid <pause dur="0.5"/> and their ankles may swell from oedema <pause dur="0.6"/> now we don't actually cover oedema as a subject <pause dur="0.3"/> # but again it's something you should know about <pause dur="0.6"/> and they're going to have the opposite here basically so they may put on weight <pause dur="0.3"/> their blood pressure will go up so they'll be hypertensive <pause dur="0.5"/> and then # this goes to the fluid in the lungs you may be able to hear

crackling in the lungs <pause dur="0.5"/> so that's the sort of things to look out for if you think somebody's got too much or too little fluid <pause dur="1.3"/><kinesic desc="changes slide" iterated="n"/> so how does the nephron control your fluid balance then <pause dur="1.2"/> so there's three main processes and these are the ones we're going to look at today <pause dur="0.8"/> you've got filtration <pause dur="0.2"/> we touched on this a little bit last week with glomerular structure but we're going to cover it a bit more today <pause dur="0.8"/> and the main aim of this is to sieve the <trunc>plas</trunc> the blood you want to sieve the blood <pause dur="0.3"/> so that you end up with # <pause dur="0.8"/> a protein-free plasma effectively all the plasma goes into the filtrate but not the proteins <pause dur="1.9"/> the nephron then has two very important functions <pause dur="0.6"/> one <trunc>i</trunc> is <trunc>cun</trunc> <pause dur="0.2"/> # secretion <pause dur="0.3"/> so it can secrete things into the # glomerular filtrate <pause dur="0.2"/> which will become urine <pause dur="0.5"/> so # has a role in P-H regulation <pause dur="0.4"/> and particularly here <pause dur="0.3"/> if you've got # foreign substances or drug metabolites you want to get rid of <pause dur="0.3"/> they may be secreted into the nephron <pause dur="0.8"/> and tubular reabsorption <pause dur="0.7"/> so <pause dur="0.2"/> we filter if you

remember last week i was telling you that we filter the whole of our blood volume every five minutes <pause dur="0.4"/> and that accounts for a hundred-and-eighty litres a day <pause dur="0.7"/> 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 <trunc>th</trunc> your kidneys <pause dur="0.3"/> is reabsorbed and that goes for everything on the whole <pause dur="0.4"/> unless it's a toxic substance you want to get rid of <pause dur="0.5"/> so everything so things like <pause dur="0.3"/> # most of the sodium you filter <pause dur="0.3"/> is reabsorbed you're only getting rid of half a per cent of the sodium that gets filtered in a day <pause dur="0.6"/> you get rid of more urea and that becomes important later in the course <pause dur="0.7"/> you reabsorb all your glucose you shouldn't have any glucose in your urine <pause dur="0.3"/> if you do that <trunc>stri</trunc> # will indicate diabetes mellitus <pause dur="0.7"/> and ninety-nine per cent of the water so you're only getting rid of # out of every hundred ml you filter you only pass one ml of urine <pause dur="0.8"/> and these two <pause dur="0.3"/> very much go together you'll see the

secretion and reabsorption occur in similar regions of the nephron <pause dur="0.4"/> and sometimes they're actually linked together <pause dur="0.7"/> # <pause dur="0.4"/> not going to go into detail of those today because they come up in each separate bit of the module <pause dur="0.3"/> as we go along <pause dur="0.3"/> but <pause dur="0.2"/> it's important you remember that you <trunc>filst</trunc> have to filter it <pause dur="0.4"/> then you have the option of secreting or reabsorbing substances and those three things together <pause dur="0.4"/> are the crux of fluid # <pause dur="0.6"/> balance <pause dur="0.4"/> and the control of ions and electrolytes <pause dur="0.7"/> and then of course finally <pause dur="0.4"/> don't forget you got your urinary excretion <pause dur="0.6"/> and it's really important that you begin to get used to talking about <pause dur="0.4"/> secretion <pause dur="0.3"/> or excretion because the two are different depending on what you're talking about <pause dur="0.3"/> the excreted things are the things that in the urine that actually get removed from the body <pause dur="0.5"/> secreted things <pause dur="0.4"/> are items that go from the blood <pause dur="0.3"/> into the kidney # tubule <pause dur="2.3"/><kinesic desc="changes slide" iterated="n"/> so what exactly do i mean so here we have a schematic <pause dur="0.4"/> so this is your nephron that's your

# Bowman's capsule and your glomerular tuft <pause dur="0.7"/> and here you've got and <pause dur="0.4"/> the artery goes in you've got your afferent arteriole <pause dur="0.3"/> efferent arteriole and it comes down into the peritubular network of blood vessels <pause dur="1.1"/> and you've got these three substances blue ones pink ones and green ones <pause dur="0.6"/> so they all come into the glomerular tuft together <pause dur="1.5"/> and then you'll find the blue and the green ones <pause dur="0.2"/> are filtered into the tubule so they're actually into the nephron lumen now <pause dur="1.2"/> but they don't behave the same then <pause dur="0.6"/> we actually want to keep the blue ones or keep the majority of the blue ones <pause dur="0.3"/> so you'll find they're actually reabsorbed <pause dur="0.3"/> back from the tubule into the circulation <pause dur="1.8"/> likewise the pink ones <pause dur="0.4"/> don't get filtered at all they go round they miss the # glomerular filtration # region <pause dur="0.5"/> into the peritubular circulation <pause dur="0.3"/> and then these get secreted <pause dur="0.2"/> into the nephron <pause dur="0.8"/> so the upshot of that in this very simplistic model <pause dur="0.4"/> is that the <pause dur="0.2"/> pink ones and the green ones get excreted <pause dur="0.3"/> whereas the blue ones are

mostly if not completely reabsorbed into the blood system <pause dur="0.5"/> so that's the three <pause dur="0.8"/> main procedures <pause dur="1.2"/> so i said i'd talk about the glomerulus a bit more this week and how it actually does this filtration <pause dur="0.5"/><kinesic desc="changes slide" iterated="n"/> do you remember this picture from last week's lecture <pause dur="0.5"/> here's your capillary <pause dur="0.6"/> the endothelium with the capillary with # holes in it remember it's fenestrated <pause dur="0.9"/> then you've got the # basement membrane here <pause dur="0.4"/> and you got the epithelial cells which are the podocytes which are these specialized kidney cells <pause dur="1.2"/> and between them they allow things to move across <pause dur="1.2"/> now the filtration obviously occurs on the size and the shape <pause dur="0.5"/> because <kinesic desc="indicates point on slide" iterated="n"/> these holes <pause dur="0.2"/> are a physical barrier the fenestrations and the slits between the # podocytes <pause dur="0.4"/> so if you're too big you won't get across <pause dur="0.4"/> but the shape's important as well if you're flexible and can squash up as a molecule <pause dur="0.3"/> you may be theoretically too big but you may be able to squash up <pause dur="0.3"/> and fit through one of these slits or holes <pause dur="0.8"/> and the charge is important <pause dur="0.2"/> the

podocytes and the basement membrane are negative <pause dur="0.3"/> and proteins tend to be negative <pause dur="0.3"/> so that will stop help to stop proteins crossing across the glomerular <pause dur="0.4"/> # membranes <pause dur="0.3"/> because the negatives will repel each other <pause dur="2.7"/> having said that it's the podocytes that form the really restrictive layer <pause dur="0.7"/> the fenestrations <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.3"/> are bigger <pause dur="0.3"/> than the slits between the podocytes <pause dur="0.6"/> so this is a rough guide as to what's going to happen <pause dur="0.3"/> now these numbers will <pause dur="0.2"/> alter as i've just said depending on the shape and the charge of the # molecule that wants to be filtered or not <pause dur="0.6"/> but roughly anything less than seven kilodaltons is going to come across with no barriers whatsoever <pause dur="0.5"/> then you've got a grey area up to seventy kilodaltons where generally <pause dur="0.3"/> it's permeable to those <pause dur="0.3"/> and molecules less than that size in weight will generally get across <pause dur="0.4"/> and anything above seventy <pause dur="0.4"/> usually won't <pause dur="0.2"/> and that includes all the proteins so most proteins <pause dur="0.3"/> are above seventy <pause dur="0.3"/> or if they're not they have the negative charge which

will encourage them not to come across <pause dur="2.3"/> but the filtration <pause dur="0.4"/> actually depends on pressure because <trunc>th</trunc> <pause dur="0.2"/> it's acting like a sieve if you imagine now the glomerular structure's like a sieve with the holes in <pause dur="0.7"/> but you need the pressure to force things across and we're going to look at that <pause dur="0.4"/> # <pause dur="0.2"/> exactly how that works in the next couple of slides <pause dur="0.5"/> but in order to help it it's got two things <pause dur="0.5"/> one the capillary walls are a hundred times more permeable <pause dur="0.3"/> than other capillaries throughout the body <pause dur="0.9"/> and as we'll see later <pause dur="0.3"/> they've got a greater pressure the # <pause dur="0.8"/> # the pressure of blood within the arterioles in the glomerular tuft is greater so they're more permeable <pause dur="0.4"/> and the blood is at a higher pressure <pause dur="0.3"/> and those two factors together <pause dur="0.3"/> force the fluid through the glomerulus <pause dur="0.4"/> and into the kidney # <pause dur="0.2"/> nephron <pause dur="1.6"/><kinesic desc="changes slide" iterated="n"/> so okay so this is # a recap of what i've said basically <pause dur="0.6"/> you've got pressure from the artery <pause dur="0.8"/> and you've got this movement of fluid now there's two other things to take account of here <pause dur="0.6"/>

it's not a simple pressure thing <pause dur="0.4"/> remember you have fluid in the glomerulus <pause dur="0.3"/> and you have fluid within the Bowman's capsule and the kidney nephron <pause dur="1.0"/> and the <pause dur="0.2"/> both of those will exert an hydrostatic pressure <pause dur="1.5"/> so the the <pause dur="0.3"/> fluid that is already within the nephron <pause dur="0.3"/> will push in one direction <pause dur="0.5"/> the fluid that's within the <pause dur="0.2"/> capillaries <pause dur="0.3"/> will push in another direction or the interstitial fluid will push in another direction <pause dur="0.5"/> you have blood pressure to take account of <pause dur="0.6"/> and you also have these # oncotic pressures <pause dur="0.6"/> now you should have covered these and # Starling's forces in lots of detail i believe in the cardiac <pause dur="0.2"/> cardiovascular module which was last semester <pause dur="0.6"/> # but if you can't remember just <pause dur="0.2"/> remind yourself briefly of what they are <pause dur="0.4"/> but this is due to proteins <pause dur="0.4"/> proteins themselves <pause dur="0.4"/> # will cause fluid to want to move from one place to another <pause dur="0.3"/> and that's known as oncotic the pressure due to the protein <pause dur="0.5"/> # is oncotic pressure <pause dur="0.9"/><kinesic desc="changes slide" iterated="n"/> so if we move this into a glomerulus and see what that actually looks

like here <pause dur="1.3"/> as you can see <pause dur="0.4"/> this is your glomerular going with your blood flow coming in and out <pause dur="0.3"/> so you've got your blood pressure <pause dur="0.2"/> represented here by <pause dur="0.2"/> these # <pause dur="0.2"/> numbers <pause dur="0.3"/> so you've got your blood pressure <pause dur="0.2"/> into your <pause dur="0.2"/> # <pause dur="0.7"/> kidney tubule <pause dur="1.3"/> you have the hydrostatic pressure <pause dur="0.4"/> exerted here by the fluid that's already in the tubule <pause dur="0.4"/> pushing back <pause dur="2.2"/> and then you've got the oncotic pressure from the plasma proteins <pause dur="0.7"/> # <pause dur="0.4"/> there are lots of proteins in here <kinesic desc="indicates point on slide" iterated="n"/><pause dur="0.5"/> and there are no proteins unless something's wrong in here <kinesic desc="indicates point on slide" iterated="n"/><pause dur="0.4"/> so if we move on to the <pause dur="0.3"/> 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 <pause dur="0.4"/> but remember <pause dur="0.5"/> that you've got blood pressure one way <pause dur="0.2"/> hydrostatic pressure the other way <pause dur="0.3"/> and oncotic pressure the other way <pause dur="0.6"/> and the oncotic pressure works like this <pause dur="0.4"/> in the tubule <pause dur="0.3"/> you have very little protein two to five nanograms per ml <pause dur="0.4"/> but in the plasma you've got six to eight <pause dur="0.4"/> grams <pause dur="0.4"/> so that's a huge huge <trunc>th</trunc> # <pause dur="0.3"/> variation in the amount of

protein <pause dur="0.4"/> and what that means is that the water in order to equal out the protein concentrations <pause dur="0.3"/> the water tries to move from the kidney tubule <pause dur="0.4"/> into the plasma <pause dur="0.4"/> and that will exert a pressure <pause dur="0.3"/> because obviously it doesn't go back that way naturally <pause dur="0.6"/> so when you put these together <pause dur="0.9"/> you actually find if you add these sums up you can see the numbers are there <pause dur="0.3"/> you've only got a ten <trunc>millime</trunc> <pause dur="0.2"/> # millimetres of mercury pressure <pause dur="0.4"/> forcing stuff <pause dur="0.4"/> into the tubule <pause dur="0.3"/> that's not very much that's quite a low pressure <pause dur="0.6"/> but remember i said that the <pause dur="0.5"/> capillaries are more permeable than normal <pause dur="0.3"/> and remember the glomerular structure's like a ball of wool so you've got an awful lot of capillaries <pause dur="0.3"/> within the glomerulus <pause dur="0.4"/> that # <pause dur="0.2"/> large surface area <pause dur="0.3"/> actually causes you to be able to filter a lot of # <pause dur="0.2"/> blood <pause dur="0.3"/> within a small space of time <pause dur="0.3"/> as i've already said it's a hundred-and-eighty litres a day <pause dur="1.7"/><kinesic desc="changes slide" iterated="n"/> okay so we come on to the <pause dur="0.4"/> glomerular filtration rate <pause dur="0.7"/> and that's the rate that you are able to filter blood <pause dur="0.4"/> and

produce a glomerular filtrate <pause dur="0.5"/> quite <pause dur="0.5"/> reasonably self-explanatory <pause dur="1.5"/> now in a male <pause dur="0.2"/> it's about a hundred-and-fifty mls per minute <pause dur="0.6"/> and you see i've written it up here it's a hundred-and-fifty mls per minute <pause dur="0.6"/> and that's the surface area of a man <pause dur="0.7"/> an average man <pause dur="0.7"/> now most people will talk about <pause dur="0.2"/> # G-F-Rs <pause dur="0.3"/> as just like mls per minute <pause dur="0.2"/> most of the nephrologists will most normal clinicians will <pause dur="0.4"/> but it's important to remember its correct units have a surface area attached to them <pause dur="0.5"/> and this becomes <trunc>im</trunc> <pause dur="0.3"/> particularly important when you look at neonates <pause dur="0.4"/> and old people because obviously their surface area if you're very small are very <trunc>sma</trunc> <pause dur="0.3"/> # <trunc>sm</trunc> small <pause dur="0.2"/> old frail lady or small baby <pause dur="0.4"/> becomes important <pause dur="0.4"/> 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 <pause dur="0.2"/> mls per minute <pause dur="0.3"/> and not mls per minute per surface area so it's <pause dur="0.4"/> if you can't remember it's one-point-seven-three <pause dur="0.3"/> an average man <pause dur="0.3"/> you it's all right if you put per surface area

i'll let you off on that one <pause dur="0.4"/> but it is important to remember that's its correct units <pause dur="0.6"/> and again it's a bit less in females <pause dur="0.3"/> and it decreases with age as you get older <pause dur="3.5"/><kinesic desc="changes slide" iterated="n"/> okay now your G-F-R actually remains constant your blood pressure goes up and down <trunc>dur</trunc> out the day goes up and down depending on what you're doing <pause dur="0.5"/> but your G-F-R <pause dur="0.9"/> tries to remain as constant as possible <pause dur="1.1"/> and it does this <trunc>be</trunc> <pause dur="0.2"/> by dilating the arteries if you remember you have an arteriole in and out <pause dur="0.4"/> and there are ways of controlling <pause dur="0.4"/> # both the efferent and the afferent arterioles <pause dur="0.5"/> and that's how it regulates blood pressure <pause dur="1.4"/> or or adapts to blood pressure rather <pause dur="0.5"/> so if we have a look here if your blood pressure increased <pause dur="0.5"/> you've got more pressure in the glomerular tuft <pause dur="0.3"/> in theory <pause dur="0.4"/> which would force more fluid through <pause dur="0.5"/> # into the tubules and increase your G-F-R <pause dur="0.7"/> that would be what you would expect to happen <pause dur="0.5"/> but it doesn't happen because this is what happens here this is a normal

glomerulus say you've got <pause dur="0.4"/> in and out arterioles at roughly equal # <pause dur="0.2"/> sizes <pause dur="0.4"/> and that's your normal <pause dur="0.2"/> blood flow and normal pressure <pause dur="1.0"/> if your blood pressure goes up <pause dur="0.4"/> a series of mechanisms come into play <pause dur="0.4"/> which actually constrict the afferent arteriole <pause dur="0.5"/> which restricts the amount of blood that flows into the glomerular tuft <pause dur="0.4"/> if you restrict the blood <pause dur="0.3"/> that effectively compensates for the increased blood pressure <pause dur="0.3"/> and so you maintain the amount of force that's provided by the blood <pause dur="0.5"/> # as the same <pause dur="0.7"/> likewise it works in reverse if your B-P <pause dur="0.3"/> drops <pause dur="0.4"/> you would expect if there's less pressure your <trunc>g</trunc> # G-F-R's going to drop <pause dur="0.7"/> now that's seriously we don't want that to happen because there are <trunc>reas</trunc> times when your blood pressure drops <pause dur="0.4"/> and you don't want your kidneys to stop working because if your G-F-R <pause dur="0.4"/> drops to almost nothing <pause dur="0.5"/> and you stop making urine your kidneys fail quite quickly <pause dur="0.3"/> and although it might not be # a failure forever it's a serious medical condition so the body doesn't

want that to happen <pause dur="0.3"/> so it wants to keep the pressure within the glomerulus <pause dur="0.2"/> high so that filtration goes on as normal <pause dur="0.4"/> so it does the opposite there <pause dur="0.5"/> and this time it dilates the afferent arteriole <pause dur="0.5"/> and # you get far more blood flow going through into the glomerulus <pause dur="0.3"/> and that compensates for the change in pressure keeps the pressure up <pause dur="0.3"/> and the G-F-R stays the same <pause dur="1.0"/> so generally throughout the day whatever happens to our blood pressure our G-F-R's going to be constant <pause dur="1.7"/><kinesic desc="changes slide" iterated="n"/> # <pause dur="0.9"/> that's what i said <pause dur="0.7"/> # <pause dur="0.6"/> 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 <pause dur="0.5"/> but there are drugs that regulate # <pause dur="0.3"/> blood pressure <pause dur="0.3"/> or # arteriole constriction or dilatation <pause dur="0.6"/> don't worry about what they are yet they're listed here simply 'cause i took it out of a book <pause dur="0.3"/> some of these will be pointed out to you as the course goes through <pause dur="0.5"/> but if certain drugs alter your arteriole pressure in your glomerulus <pause dur="0.4"/> either by constricting or dilating <pause dur="0.2"/>

the efferent or the <trunc>ef</trunc> afferent arterioles <pause dur="0.3"/> that will affect G-F-R <pause dur="0.2"/> and may affect kidney function so you just need to bear that in mind <pause dur="0.8"/><kinesic desc="changes slide" iterated="n"/><vocal desc="clears throat" iterated="n"/><pause dur="1.3"/> 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 <pause dur="1.4"/> so if you have an obstruction <pause dur="0.5"/> somewhere within the # urinary system <pause dur="0.4"/> that causes the pressure of the fluid within the tubule to build up <pause dur="0.6"/> the hydrostatic pressure then backs up <pause dur="0.5"/> and causes a greater force of pressure <pause dur="0.3"/> from within the tubule <pause dur="0.2"/> out through the glomerulus <pause dur="0.3"/> preventing filtration occurring <pause dur="0.3"/> so in that case your G-F-R will drop <pause dur="0.7"/> so somebody who has a blockage a build-up of fluid <pause dur="0.5"/> will their G-F-R drops <pause dur="0.9"/> again obviously changes in the glomerulus are an important # factor to bear in mind <pause dur="0.5"/> so <pause dur="0.2"/> if your glomerulus <pause dur="0.2"/> blocks up effectively your G-F-R will drop <pause dur="0.3"/> your urine output will drop and # you have kidney problems <pause dur="0.3"/> but likewise if there's damage that causes it to leak <pause dur="0.4"/> then <trunc>y</trunc> # <pause dur="0.2"/>

fluid's going to flood through your glomerulus <pause dur="0.4"/> and you're going to have an increased G-F-R and an increased urine output <pause dur="0.4"/> now those are usually reasonably obvious to spot either because something's in the <pause dur="0.4"/> urine that shouldn't be there because it's got across the glomerulus <pause dur="0.3"/> or your urine output goes up or down accordingly <pause dur="0.4"/> # <pause dur="0.4"/> and then you have to start to investigate why <pause dur="1.5"/> 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 <pause dur="0.5"/> # ability <pause dur="0.4"/> # you know 'cause # people with only one kidney either because they've lost one through illness or # <pause dur="0.5"/> they've had a transplant you only get one when you have a transplant <pause dur="0.3"/> they function perfectly well they don't have to restrict their diet or anything particularly <pause dur="0.4"/> to compensate for having lost half of their renal function effectively <pause dur="0.7"/> but a small change can have a problem <pause dur="0.3"/> or or can <pause dur="0.8"/> # manifest itself as something obvious <pause dur="0.4"/> so here we've got <pause dur="0.4"/> two

G-F-Rs the same <pause dur="0.5"/> and you would normally produce one ml of # <pause dur="0.2"/> urine per minute that's what's our normal production <pause dur="0.7"/> but you can see if you start producing two mls of urine per minute that's actually <pause dur="0.3"/> a small amount here so you're only altering your reabsorption by one ml and your excretion by one ml <pause dur="0.4"/> but that's actually doubling your urine output <pause dur="0.3"/> so although per minute that doesn't seem much you take that into account over a day <pause dur="0.3"/> that's a huge volume change </u><gap reason="break in recording" extent="uncertain"/> <u who="nf0368" trans="pause"><kinesic desc="projector is on showing slide" iterated="n"/> so moving on now to renal clearance <pause dur="0.5"/> and that's simply the ability of your kidneys to clear <pause dur="0.4"/> whatever you're talking about <pause dur="0.3"/> from the blood <pause dur="1.6"/> and it's an actual quantity and again it's got units it's <pause dur="0.7"/> per ml of plasma per time and you'll see why in a minute <pause dur="0.5"/> and it's completely independent <pause dur="0.4"/> of the amount of urine you produce <pause dur="0.5"/> so if you clear ten milligrams of something <pause dur="0.3"/> per minute <pause dur="0.7"/> it's going to be ten milligrams per minute whether you're peeing <pause dur="0.3"/> one litre in an hour <pause dur="0.3"/> or two litres in an hour obviously it's more dilute <pause dur="0.4"/> in the urine <pause dur="0.3"/>

but what you clear from the blood stays the same <pause dur="1.0"/> is that clear <pause dur="1.0"/> so the urine <pause dur="1.0"/> concentration has nothing to do with your renal clearance <pause dur="0.4"/> that's a <trunc>b</trunc> # that relates to the amount you clear from the plasma or the blood <pause dur="2.2"/> now <pause dur="0.4"/> obviously there are times when we want to calculate how effectively the kidneys are working <pause dur="0.7"/> the times when we want to know what the glomerular filtration rate is <pause dur="0.3"/> there are times when we want to know what the renal blood flow <pause dur="0.4"/> # <pause dur="0.2"/> is <pause dur="0.3"/> and we can calculate that as well and we'll come on to that <pause dur="0.3"/> towards the end <pause dur="0.5"/> but the G-F-R's a really useful one to calculate <pause dur="0.2"/> if you have glomerular diseases <pause dur="0.3"/> you're going to notice a change in the G-F-R so it's something that clinicians do regularly <pause dur="0.9"/> so in order to calculate that if something is cleared <pause dur="0.4"/> # <pause dur="0.3"/> from the blood by filtration alone <pause dur="0.7"/> then <pause dur="0.2"/> the rate that it's its renal clearance equals the glomerular filtration rate <pause dur="0.7"/> so if it's <trunc>c</trunc> # <pause dur="0.2"/> purely filtered <pause dur="0.7"/> the rate at which it's filtered <pause dur="0.3"/> is the rate it's cleared from the

blood <pause dur="1.0"/> okay <pause dur="1.0"/> so <pause dur="0.3"/><kinesic desc="changes slide" iterated="n"/> how do we calculate this <pause dur="1.3"/> and one thing i've put up here it's important to remember <pause dur="0.6"/> that this is <pause dur="0.3"/> comes in remember i said remember to get excretion and secretion the right way round <pause dur="0.5"/> also remember to <pause dur="0.3"/> start getting in the habit of using urine <pause dur="0.3"/> and filtrate in the right <pause dur="0.6"/> # context <pause dur="0.9"/> urine is <shift feature="voice" new="laugh"/>only urine <vocal desc="laughter" iterated="y" n="sl" dur="2"/> <shift feature="voice" new="normal"/>urine is only urine <pause dur="0.3"/> once the filtrate enters the collecting system <pause dur="0.3"/> until it enters the collecting tubules <pause dur="0.2"/> anything before that is technically known as filtrate <pause dur="0.9"/> # so when i'm talking about stuff that's within the glomerular <pause dur="0.4"/> <trunc>neph</trunc> # the nephrons rather <pause dur="0.2"/> that's always filtrate until it enters the collecting system <pause dur="1.0"/> so if something is purely filtered <pause dur="0.4"/> not reabsorbed into the bloodstream <pause dur="0.4"/> the concentration in the filtrate is exactly the same as the concentration in the plasma <pause dur="1.1"/> 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 <pause dur="0.9"/> we don't want anything that's # absorbed or

secreted <pause dur="0.6"/> and we don't want it to be made or metabolized by the kidneys <pause dur="0.7"/> and that's actually quite a limiting # selection of finding things to do like that <pause dur="0.7"/><kinesic desc="changes slide" iterated="n"/> so we have inulin <pause dur="0.5"/> 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 <pause dur="0.6"/> 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 <pause dur="0.7"/> but creatinine <pause dur="0.8"/> is easy <pause dur="0.5"/> that's a <trunc>br</trunc> a natural breakdown subject # <trunc>sub</trunc> <pause dur="0.2"/> # <pause dur="0.3"/> substance <pause dur="0.4"/> we've got here it's freely filtered <pause dur="0.4"/> it's not reabsorbed so that fulfills <unclear>all</unclear> the criterias <pause dur="0.8"/> we do have a little bit of secretion of it <pause dur="0.7"/> that's not a huge problem and i'll explain why on the next couple of slides <pause dur="0.3"/> but you have to bear that in mind we do secrete a small amount of creatinine <pause dur="0.3"/> so it's not an ideal substance but it's the best we've got <pause dur="0.8"/><kinesic desc="changes slide" iterated="n"/> so how do you calculate it <pause dur="0.2"/> 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 <pause dur="0.4"/> afterwards but i'll take you through them now <pause dur="0.6"/> so here are our G-F-R <pause dur="0.4"/> you know i've put mls per minute i haven't bothered with the surface area there 'cause <pause dur="0.2"/> the calculation's easier <pause dur="0.6"/> # to explain that way <pause dur="0.5"/> this is the volume of # urine so you have to measure how much urine you're producing over a certain time <pause dur="0.6"/> and work out the rate per minute <pause dur="0.9"/> this is the creatinine concentration <pause dur="0.4"/> in the urine <pause dur="0.6"/> so just want that as a concentration <pause dur="0.5"/> and this is the plasma concentration <pause dur="0.3"/> so you want to compare how much is in the urine <pause dur="0.4"/> to how much is in the plasma basically <pause dur="1.1"/> and that will give you the rate at which it's being filtered and you can see the units <trunc>cal</trunc> <pause dur="0.4"/><kinesic desc="indicates point on slide" iterated="n"/> these units <trunc>c</trunc> # cancel out so you're left with mls per minute <pause dur="1.2"/> and that # calculation here <kinesic desc="indicates point on slide" iterated="n"/><pause dur="0.5"/> this i've got down to determine G-F-R <pause dur="0.4"/> but you can replace that with renal clearance <pause dur="0.3"/><kinesic desc="indicates point on slide" iterated="n"/> this <trunc>calculatio</trunc> or this equation <pause dur="0.3"/> will calculate the renal clearance of anything <pause dur="0.5"/> you can look at how much is in the urine <pause dur="0.3"/> versus how much is in the

blood <pause dur="0.5"/> now or plasma we're using this for creatinine <pause dur="0.3"/> so that equates to G-F-R but if it was a different substance that wasn't completely cleared <pause dur="0.3"/> then it would be the renal clearance number <pause dur="0.5"/> so just <trunc>r</trunc> <pause dur="0.2"/> bear that in mind <pause dur="0.7"/><kinesic desc="changes slide" iterated="n"/> so is it a good estimate remember i said that some of it was secreted as well <pause dur="1.6"/> it's not a big problem <pause dur="0.6"/> the assay that measures # plasma creatinine <pause dur="0.2"/> overestimates <pause dur="0.8"/> so the two of them <pause dur="0.3"/> cancel each other out the bit of secretion that comes from the body <pause dur="0.3"/> versus the overestimation of the plasma creatinine <pause dur="0.3"/> tend to cancel each other out <pause dur="0.4"/> # so it's not a huge problem <pause dur="2.0"/> however <pause dur="0.5"/> it can become a problem when you have a # <pause dur="0.5"/> an illness <pause dur="0.8"/> so if the # <pause dur="1.1"/> if the G-F-R drops <pause dur="0.4"/> you get more secreted by the kidneys to try and keep the blood level <pause dur="0.4"/> equal <pause dur="0.8"/> the idea is <pause dur="0.3"/> # you have the ability to secrete so that if for some reason <pause dur="0.3"/> your filtration isn't working very well <pause dur="0.3"/> you don't want the creatinine to build up in your blood <pause dur="0.4"/> so the the body says oh that's doesn't matter <pause dur="0.3"/> if it's

not being filtered that's fine i'll send it a bit further round the # tubular <pause dur="0.3"/> capillary network <pause dur="0.2"/> and secrete it directly into the tubules <pause dur="0.7"/> obviously if your secretion goes up <pause dur="0.4"/> then when i said that secretion and overestimation of plasma cancel each other out that doesn't occur any more <pause dur="0.5"/> so if you have somebody that you know has glomerular filtration problems <pause dur="0.5"/> then creatinine is not a good estimate of G-F-R <pause dur="1.8"/> the other problem <pause dur="0.4"/> i haven't actually # <pause dur="0.3"/> got the graph with me here but it's in nearly every textbook <pause dur="0.7"/> in order for you to see a change <pause dur="0.4"/> # in plasma creatinine levels because of this ability to secrete <pause dur="0.4"/> your G-F-R has to drop by about fifty per cent <pause dur="0.8"/> so if you're simply <trunc>measure</trunc> <pause dur="0.3"/> # plasma creatinine <pause dur="0.3"/> and you'll find this comes back week after week in the group work you get <pause dur="0.3"/> urea and electrolytes and creatinine <pause dur="0.5"/> the creatinines will go up eventually but because of your ability <trunc>se</trunc> to secrete it <pause dur="0.4"/> they will only go up when you've lost half of your G-F-R capacity or

<sic corr="thereabouts">theresabouts</sic> <pause dur="0.8"/> so if you simply look at plasma creatinine levels <pause dur="0.4"/> # they could be masking an underlying kidney condition so you just have to bear <pause dur="0.4"/> because the creatinine's normal <pause dur="0.3"/> it doesn't necessarily rule out some problem with the # <pause dur="0.5"/> kidneys <pause dur="0.4"/> although it is used routinely <pause dur="0.5"/> but that does mean the moment you see the plasma creatinine to go up <pause dur="0.3"/> you know you've got a real problem with your kidneys <pause dur="1.6"/> this is another thing to bear in mind it depends on muscle mass it's a breakdown of <pause dur="0.2"/> muscle mass <pause dur="0.3"/> little old ladies <pause dur="0.3"/> Asian people they have a completely different muscle mass from the average white person <pause dur="0.3"/> and you have to bear that in mind their creatinines may be different as a consequence <pause dur="1.8"/> ah i've said that already <pause dur="1.1"/><kinesic desc="changes slide" iterated="n"/> i'm not going to <pause dur="0.3"/> discuss this now <pause dur="0.7"/> this table looks at <pause dur="0.3"/> # whether something is filtered or reabsorbed or secreted or a combination of which <pause dur="0.4"/> and gives you <pause dur="0.6"/> # examples here tells you what happens to the substance examples here <pause dur="0.5"/> and then what you would see in the renal vein <pause dur="0.4"/>

versus the renal artery is the concentration going to be higher or lower or the same <pause dur="0.7"/> and <trunc>ha</trunc> what sort of renal clearance you would expect in comparison to a G-F-R <pause dur="0.8"/> now what i want you to do is have a look at this and make certain for each of those <pause dur="0.3"/> you can work out <pause dur="0.3"/> why when i said this one isn't filtered <pause dur="0.4"/> # it's going to be the same in the artery versus the brain and # <pause dur="0.2"/> <vocal desc="laugh" iterated="n"/> <pause dur="0.4"/> <shift feature="voice" new="laugh"/>artery <shift feature="voice" new="normal"/>versus the vein rather and have no renal clearance <pause dur="0.3"/> and do that for all of them <pause dur="0.4"/> if you can't work out <pause dur="0.6"/> why that table's as it is <pause dur="0.4"/> 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 <pause dur="0.3"/> 'cause it is important that you understand <pause dur="0.4"/> # secretion absorption and filtration and excretion <pause dur="0.4"/> and i'll happily <vocal desc="clears throat" iterated="n"/> excuse me i'll happily go over that <pause dur="0.2"/> later on this morning <pause dur="1.3"/><kinesic desc="changes slide" iterated="n"/> so i said i wanted to calculate renal blood flow occasionally <pause dur="0.3"/> <vocal desc="clears throat" iterated="n"/><pause dur="1.0"/> and this is the rate at which the blood flows through the kidneys pretty obvious how much goes in versus how much comes

out <pause dur="0.6"/><vocal desc="clears throat" iterated="n"/><pause dur="1.3"/> now in order to do this we actually use # <pause dur="0.8"/> a function of the kidneys <pause dur="0.5"/> when the blood flows into the glomerulus <pause dur="0.3"/> not all of it is filtered obviously you have a flatbed of # <pause dur="0.9"/> # endothelium <pause dur="0.2"/> basement membrane and epithelium <pause dur="0.2"/> and you have blood flow over the top <pause dur="0.7"/> now not all of that blood flowing over the top <pause dur="0.4"/> is going to be in contact with the capillaries and is going to be able to be filtered through <pause dur="0.6"/> the the blood in the centre of the <trunc>capilla</trunc> of the arteriole <pause dur="0.3"/> is basically going to go whizzing past over the top of the meshwork of # <pause dur="0.2"/> sieving apparatus <pause dur="0.5"/> so only the <pause dur="0.2"/> a proportion of the blood <pause dur="0.3"/> is actually filtered at any one time <pause dur="0.6"/> and i'll show you <pause dur="0.4"/> on almost the last slide what it is but roughly that works out to <pause dur="0.2"/> eighty per cent goes whizzing straight past into the peritubular circulation <pause dur="0.3"/> and twenty per cent is filtered into the <pause dur="0.4"/> # nephron <pause dur="0.4"/> and that's known as the filtration fraction <pause dur="1.8"/> now we can use this <vocal desc="clears throat" iterated="n"/> the consequences are if you look at <trunc>e</trunc> urea <pause dur="0.6"/> fifty per cent # <pause dur="0.8"/> of urea

well the urea's filtered but then some of it is reabsorbed so <pause dur="0.3"/> you can see that some goes through the kidneys <pause dur="0.4"/> and some # is reabsorbed <pause dur="0.6"/> but as it's not secreted back into the kidneys <pause dur="0.6"/> only the proportion that actually gets filtered can ever get cleared in one time <pause dur="0.9"/> so the only way you have of clearing urea is to filter it though the glomerulus <pause dur="0.6"/> so if only twenty per cent of your blood is going into the <trunc>glomeru</trunc> through the glomerulus into the tubule network <pause dur="0.5"/> you need five passes of blood to clear it of <trunc>uri</trunc> urea effectively <pause dur="0.4"/> okay <pause dur="1.5"/><kinesic desc="changes slide" iterated="n"/> however <pause dur="0.2"/> some substances if they're filtered and secreted <pause dur="0.6"/> or just completely secreted on their own <pause dur="0.6"/> you only need a single pass <pause dur="0.6"/> so if the substance is filtered through the glomerulus into the tubule network <pause dur="0.7"/> twenty per cent of it will get filtered the other eighty per cent of it goes round into the peritubular circulation <pause dur="0.8"/> that eighty per cent that's escaped the first pass into the peritubular circulation <pause dur="0.3"/> will then be secreted directly into

the tubules <pause dur="0.7"/> so the whole hundred per cent of that particular substance <pause dur="0.3"/> gets into the nephron <pause dur="0.4"/> in one <pause dur="0.6"/> go of the blood <pause dur="0.4"/> through the nephron circulation <pause dur="1.2"/> does that <pause dur="0.5"/> make sense <pause dur="0.5"/> okay <pause dur="0.6"/> and we can use that to work out the renal blood flow <pause dur="0.7"/> and one substance that <pause dur="0.3"/> does this is P-A-H <pause dur="1.6"/><kinesic desc="changes slide" iterated="n"/> okay so here we have <pause dur="0.3"/> green blobs going into the glomerulus <pause dur="0.3"/> some <pause dur="0.6"/> gets filtered <pause dur="0.2"/> some goes into the circulation <pause dur="0.8"/> but as it comes into the circulation when it gets to the correct part of the nephron <pause dur="0.3"/> it's secreted into the tubule <pause dur="0.5"/> the consequences are <pause dur="0.4"/> you have P-A-H coming in <pause dur="0.6"/> P-A-H going out in urine <pause dur="0.5"/> but hardly any at all in the renal vein <pause dur="1.8"/><kinesic desc="changes slide" iterated="n"/> and we use this <pause dur="0.4"/> so we calculate in this case renal clearance <pause dur="0.4"/> which was i told you just the amount that's # filtered <pause dur="0.4"/> effectively <pause dur="0.6"/> equals the G-F-R <pause dur="0.3"/> of P-A-H <pause dur="0.5"/> plus the amount secreted and equals what we call the renal plasma flow <pause dur="2.0"/> so you calculate the renal clearance of P-A-H <pause dur="0.4"/> exactly the same way as we used creatinine to calculate G-F-R <pause dur="0.7"/> so if you want to work out the calculation here

you've got the volume of urine <pause dur="0.6"/> the urine concentration of P-A-H <pause dur="0.4"/> the plasma concentration of P-A-H <pause dur="0.3"/> and that gives you the renal clearance of P-A-H <pause dur="0.4"/> which equals the renal plasma flow <pause dur="1.1"/> okay <pause dur="2.5"/><kinesic desc="changes slide" iterated="n"/> however <pause dur="0.3"/> 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 </u><gap reason="break in recording" extent="uncertain"/> <u who="nf0368" trans="pause"> we've calculated <pause dur="0.4"/> the # <pause dur="1.0"/> # clearance rate from the plasma <pause dur="0.5"/> to <trunc>con</trunc> # to turn that into blood you need to just allow for the # number of red blood cells <pause dur="0.3"/> so if you do a haematocrit <pause dur="0.4"/> if you find that say forty-five per cent's red blood cells <pause dur="0.5"/> # and fifty-five per cent is plasma <pause dur="0.4"/> the renal clearance of P-A-H <pause dur="0.5"/> is fifty-five per cent <pause dur="0.4"/> of what the # renal blood flow is <pause dur="0.2"/> so all you simply do to your simple calculation <pause dur="0.5"/> is you take your <pause dur="0.5"/> # renal clearance of P-A-H which is about six-hundred mls per minute <pause dur="1.0"/> and you multiply that you just do <vocal desc="clears throat" iterated="n"/> correction factor to allow for fifty-five per cent <pause dur="0.7"/> so in this case using those numbers your renal blood flow <pause dur="0.3"/> is just over a litre <pause dur="0.2"/> per

minute <pause dur="0.6"/> okay <pause dur="0.7"/><kinesic desc="changes slide" iterated="n"/> you're not going to be used asked to calculate all of these in exams or anything so don't worry <pause dur="2.2"/> so remember i said we use the filtration fraction the fact that only twenty per cent of the # <pause dur="0.9"/> blood gets filtered at only one time <pause dur="0.6"/> you can backtrack that i told you it was twenty per cent but you can actually calculate it as well <pause dur="0.7"/> so if you take your <pause dur="0.2"/> glomerular filtration rate <pause dur="0.7"/> and compare that <pause dur="0.4"/> with your renal plasma flow <pause dur="0.8"/> that will tell you how much of the blood <vocal desc="clears throat" iterated="n"/> was filtered the first time round <pause dur="0.8"/> so if we put our numbers in <pause dur="0.6"/> that's your standard G-F-R <pause dur="0.6"/> 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 # <pause dur="0.9"/> so that's very simple so you can actually work out <pause dur="0.4"/> the fractions <pause dur="0.3"/> and sometimes <pause dur="0.3"/> these sort of <trunc>inf</trunc> these numbers are useful <pause dur="0.3"/> if you're trying to work out what your glomerular function <pause dur="0.3"/> actually is <pause dur="2.0"/><kinesic desc="changes slide" iterated="n"/> okay <pause dur="0.2"/> we've said that <pause dur="0.6"/> <vocal desc="clears throat" iterated="n"/><pause dur="0.7"/> so if we look at secretion and

absorption now <pause dur="1.0"/> now this is what i was saying last <trunc>wi</trunc> week you have to remind yourself of active passive transport <pause dur="0.4"/> # simple diffusion <vocal desc="clears throat" iterated="n"/> cotransporters et cetera <pause dur="0.6"/> # <pause dur="0.3"/> they are all going to crop up <pause dur="0.2"/> in the later sessions of this module <pause dur="0.7"/> # but this is just to remind you that basically things go through cells <pause dur="0.3"/> or between them <pause dur="0.3"/> and they might need energy and they might not <pause dur="0.2"/> but the one thing you have to remember in the kidney <pause dur="0.4"/> is that it's arranged like this <vocal desc="clears throat" iterated="n"/><pause dur="0.5"/> so <kinesic desc="indicates point on slide" iterated="n"/> here you have <pause dur="0.4"/> this is the nephron with the # filtrate in it and cells either side <pause dur="0.5"/> <vocal desc="cough" iterated="n"/> excuse me <pause dur="0.9"/> <kinesic desc="indicates point on slide" iterated="n"/> this is your capillary <pause dur="0.6"/> # <pause dur="0.4"/> and obviously that is semipermeable and you have your interstitial fluid <pause dur="1.1"/> now things may go between the cells in either direction <pause dur="0.5"/> and just diffuse simply between the cells <pause dur="0.2"/> that's quite simple <pause dur="0.2"/> <vocal desc="clears throat" iterated="n"/> <pause dur="0.5"/> however if an active transport is needed <pause dur="0.5"/> you need to have some mechanism to get it into your tubular cell <pause dur="1.0"/> and you need <pause dur="0.2"/> another transport mechanism <pause dur="0.3"/> to get it out <pause dur="0.5"/> and then obviously

it can simply diffuse into the blood if that's where it's going <pause dur="0.5"/> but it's really important to remember <pause dur="0.4"/> when we're talking about whether things are secreted <pause dur="0.3"/> or reabsorbed in the kidney <pause dur="0.3"/> they have to go from the <pause dur="0.3"/> either from the <pause dur="0.3"/> # <pause dur="0.8"/> lumen of the nephron the filtrate <pause dur="0.4"/> into a tubular cell <pause dur="0.3"/> across the cell <pause dur="0.3"/> and out the other side so you have transport mechanisms on both sides <pause dur="0.4"/> and likewise if they're going <pause dur="0.3"/> into the tubule <pause dur="0.4"/> # lumen you have again <pause dur="0.5"/> out of the blood into interstitial fluid and then you've got two <pause dur="0.5"/> membranes it has to get across <pause dur="0.6"/> and you have to remember that <pause dur="1.6"/><kinesic desc="changes slide" iterated="n"/> so okay so these are the things i want you to <pause dur="0.3"/> go home with and hopefully remembered <pause dur="0.5"/> we've got these four processes occurring <pause dur="0.3"/> and remember as mentioned get your secretion and excretion right <pause dur="0.4"/> 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 <trunc>i</trunc> it does happen <pause dur="0.4"/> and again just remember <pause dur="0.3"/> whether you're talking about filtrate or urine <pause dur="0.8"/> and then these are the things that we can calculate G-F-R is the number that you're most <pause dur="0.3"/> often going to come across <pause dur="0.6"/> but using <pause dur="0.2"/> the # <pause dur="0.4"/> mechanisms of calculating the G-F-R you can calculate these other things as well <pause dur="1.8"/><kinesic desc="changes slide" iterated="n"/> and then next week we're going to talk about # <pause dur="0.7"/> blood pressure control <pause dur="0.3"/> in more detail and look at sodium <trunc>mechan</trunc> well i'm not talking about it next week # <pause dur="0.3"/> somebody from <gap reason="name" extent="1 word"/> is <pause dur="0.4"/> but we'll pick up and take it further down and look at the regulation of sodium <pause dur="1.4"/> so <pause dur="0.3"/> i've overrun a little bit <pause dur="0.5"/> # we need to just move on <pause dur="0.5"/> reasonably swiftly to the next one so that <gap reason="name" extent="2 words"/> can come in <pause dur="0.6"/> # but i just have to sort this out a minute <pause dur="1.2"/> so you've got a couple of minutes while i swap files over on here