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<title>Concentration and Dilution of Urine</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

upon written application to any of the holding bodies.

The BASE corpus is freely available to researchers who agree to the

following conditions:</p>

<p>1. The recordings and transcriptions should not be modified in any


<p>2. The recordings and transcriptions should be used for research purposes

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

<p>3. The recordings and transcriptions should not be reproduced in full for

a wider audience/readership, although researchers are free to quote short

passages of text (up to 200 running words from any given speech event)</p>

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

publications arising from analysis of the corpus</p><p>

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="00:48:45" n="8724">


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



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



<person id="nf0440" role="main speaker" n="n" sex="f"><p>nf0440, main speaker, non-student, female</p></person>

<person id="sm0441" role="participant" n="s" sex="m"><p>sm0441, participant, student, male</p></person>

<personGrp id="ss" role="audience" size="l"><p>ss, audience, large group </p></personGrp>

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

<personGrp role="speakers" size="4"><p>number of speakers: 4</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="nf0440"><kinesic desc="projector is on showing slide" iterated="n"/> if you're all ready to start <pause dur="0.6"/> thank you <pause dur="0.9"/> okay so we're looking about how you concentrate your urine <kinesic desc="changes slide" iterated="n"/> so we're going to look at osmolarity and urine concentration <pause dur="1.3"/> and then we're going to look at water reabsorption and what actually regulates your water reabsorption from the nephron <pause dur="0.8"/> and this brings us on to the loop of Henle in the counter current # <pause dur="0.2"/> system <pause dur="0.9"/> now you might remember that from A-level and hate it but hopefully i'm going to explain it to you <pause dur="0.4"/> but it's really quite important to that you actually understand the principle behind it <pause dur="0.4"/> i know it says in your workbook you're not covering it that's because <gap reason="name" extent="1 word"/> don't see any point in teaching it <pause dur="0.4"/> but i'm sorry everybody clinicians <pause dur="0.2"/> and myself think it's vital at this end so you do get taught it <pause dur="1.2"/> and then we're just going to finish up with what happens when it goes wrong <pause dur="0.4"/> and the two clinical conditions <pause dur="0.5"/> and these are actually covered in case studies so <pause dur="0.2"/> we skip over the # clinical conditions we're just <pause dur="0.4"/>

not too much detail in the lecture because you get them in case studies to actually look at them in more depth <pause dur="2.1"/><kinesic desc="changes slide" iterated="n"/> so if we have a look at <pause dur="0.4"/> urine production first off then <pause dur="1.6"/> so this is your you've got a huge flexibility in how much urine you do or don't produce <pause dur="0.4"/> so you've got a minimum of about <pause dur="0.3"/> point-twenty-five # point-two-five mls per minute <pause dur="0.5"/> and a maximum of twenty-five <pause dur="0.6"/> but twenty-five's a hell of a lot of urine if you've got somebody producing twenty-five mls of urine a minute <pause dur="0.5"/> # you probably want to do something about it and it's not normal to produce that much urine despite the fact that we can do <pause dur="2.4"/> normal urine production <pause dur="0.4"/> most of you probably peeing somewhere between about fifteen-hundred and two mls a day <pause dur="0.7"/> and that works out to just if it's fifteen-hundred that's a ml per minute is what you're actually producing in the kidney <pause dur="0.8"/> now this is <pause dur="0.2"/> kind of an important number because if you were producing two litres of urine a day <pause dur="0.4"/> and you'll see why on the next couple of slides <pause dur="0.3"/> that

actually means you're # peeing out isotonic urine compared to blood plasma <pause dur="0.6"/> and that doesn't matter to us # <pause dur="0.2"/> if your kidneys are operating normally that's no problem <pause dur="0.4"/> but if you're a renal patient with some impaired function <pause dur="0.4"/> # <pause dur="0.3"/> drinking two litres and therefore peeing two litres kind of <pause dur="0.4"/> takes the strain off the kidney really so <pause dur="0.4"/> if you've got somebody with impaired renal function <pause dur="0.4"/> two litres becomes more important <pause dur="1.3"/> and most of you will know this already <pause dur="0.3"/> you make more urine during the day than you do at night <pause dur="0.4"/> because most of you will be able to sleep through the night and not get up to go to the loo whereas you might go three or four times during the day or even more <pause dur="0.8"/> and if you're <pause dur="0.2"/> <trunc>pee</trunc> if you're making urine less during the night you're also excreting less salts because obviously the salts and the water go together so <pause dur="0.4"/> you <trunc>e</trunc> excrete more salts during the day <pause dur="0.2"/> and you pee more urine during the day <pause dur="0.9"/> now obviously this might change if you're a shift worker if you work

nights <pause dur="0.3"/> your system's going to readjust to it <pause dur="0.4"/> because you actually produce more water during the day <pause dur="0.3"/> because of what you do because of eating <pause dur="0.3"/> and metabolism <pause dur="0.6"/> so if you're # <pause dur="0.7"/> on the reverse system because you're a night worker then you're going to be <trunc>metaboli</trunc> <pause dur="0.2"/> <trunc>meta</trunc> metabolically more active during the night <pause dur="0.3"/> so you're going to pee during the night because effectively their days are just reversed <pause dur="0.4"/> but normal day shift workers <pause dur="0.5"/> we make more urine in the day than we do at night <pause dur="1.6"/> and this is just important here we're going to talk about A-D-H later antidiuretic hormone <pause dur="0.9"/> but the amount of solutes you excrete per day is fixed <pause dur="0.3"/> depending on your intake and what you need to get rid of <pause dur="0.4"/> it's the amount of water in your urine that varies which is why the osmolarity has to vary <pause dur="0.6"/> you don't change your concentration the amount the quantity of solutes that you want to excrete <pause dur="1.4"/><kinesic desc="changes slide" iterated="n"/> so if we just look at how flexible it is <pause dur="0.4"/> this blue bar here <pause dur="0.5"/> that's your plasma osmolarity remember i said <pause dur="0.7"/> week

before last or <pause dur="0.2"/> whichever week it was <trunc>w</trunc> session one or two <pause dur="0.3"/> your plasma osmolarity has to stay very fixed it's it's very narrow band <pause dur="0.3"/> around about two-hundred-and-eighty milliosmoles <pause dur="0.8"/> in contrast your urine can <pause dur="0.3"/> have this great range <pause dur="0.9"/> although it looks like it can make it <pause dur="0.2"/> # more concentrated <pause dur="0.3"/> relative to dilution actually it's a tenfold dilution it can manage because it can # produce thirty milliosmoles <pause dur="0.2"/> # of urine # it has can be that dilute <pause dur="0.6"/><kinesic desc="indicates point on slide" iterated="n"/> this is # <pause dur="0.8"/> a concentration that's only four times the value of plasma but it's a huge range <pause dur="2.1"/> now you can actually work out <pause dur="0.2"/> the concentration of your <pause dur="0.3"/> # <pause dur="1.2"/> osmolarity of your urine if you want to <pause dur="0.7"/> and this is what we averagely excrete a day about six-hundred milliosmoles of salt solutes <pause dur="0.4"/> # on an average normal diet over here <pause dur="0.3"/> and therefore you can just put the numbers into this equation and come up with # <pause dur="0.3"/> these simple answers so that if you excrete fifteen-hundred mls of urine <pause dur="0.4"/> then the concentration of urine's going to be that <pause dur="0.3"/>

obviously if you excrete double the amount of urine it's less <pause dur="0.4"/> # so i've just put that in <pause dur="0.4"/> for you to know about <pause dur="1.2"/> but this is important we're not going to most of what we're going to talk about today is how you regulate water <pause dur="0.3"/> via hormones and osmosis et cetera <pause dur="1.0"/> but the solute concentration will <pause dur="0.2"/> alter your alter # your urine excretion <pause dur="0.4"/> on its own independent of antidiuretic hormone and anything else that's going on <pause dur="1.1"/> so <pause dur="0.5"/><kinesic desc="changes slide" iterated="n"/> just to get the the units up here <pause dur="0.2"/> come like that but just remember that a kilogram of water <pause dur="0.3"/> is a thousand mls therefore you're actually talking of the molarity effectively it's just that osmolarity comes with slightly different units <pause dur="0.8"/> so remember i said a normal person needs to excrete on an average diet six-hundred milliosmoles <pause dur="0.9"/> and then that's your maximum urine concentration of twelve-hundred <pause dur="0.3"/> so that means to excrete that during the day <pause dur="0.3"/> you have to pass five-hundred mls of urine <pause dur="1.3"/> if for some reason <pause dur="0.4"/> you want to get rid of this <trunc>num</trunc> this amount of salt <pause dur="0.5"/>

depending on your diet or various other conditions <pause dur="0.9"/> the maximum urine concentration's still only twelve-hundred <pause dur="0.4"/> so in this case you have to # pee fifteen-hundred mls <pause dur="0.3"/> and that is totally independent of whatever else is going on if your solute concentration goes up <pause dur="0.4"/> you will need to pass more urine if nothing else changes <pause dur="2.5"/> and i've just said that <pause dur="0.8"/><kinesic desc="changes slide" iterated="n"/> so let's have a look what actually happens to water in the nephron <pause dur="0.5"/> so here we have your hundred-and-eighty litres of filtrate per day <pause dur="0.5"/> but you only get rid of one per cent which is one-point-eight here <pause dur="0.2"/> or fifteen-hundred mls that sort of <pause dur="0.2"/> # quantity <pause dur="1.7"/> now these two regions of the nephron <pause dur="0.3"/> get rid of somewhere between eighty-five and ninety per cent of the water they reabsorb it <pause dur="0.6"/> and this is done passively there's no regulation whatsoever <pause dur="0.5"/> now although <pause dur="0.3"/> # from the diuretics lecture with <gap reason="name" extent="2 words"/> if you can remember <pause dur="0.3"/> you can modify <pause dur="0.3"/> the absorption of water in these parts of the nephron <pause dur="0.3"/> that's a drug action normally you don't regulate

it whatsoever <pause dur="0.3"/> you just simply reabsorb <pause dur="0.3"/> passively <pause dur="0.3"/> all this amount of water <pause dur="2.0"/> but this is what we're going to look at <pause dur="0.2"/> this part of the nephron the collecting duct <pause dur="0.3"/> you regulate the amount of water that you reabsorb <pause dur="0.8"/> and that's the bit that we're actually going to look at the control of <pause dur="0.4"/> so you only have control of a small amount of your filtrate <pause dur="0.3"/> i haven't actually done the numbers but <pause dur="0.2"/> most of that hundred-and-eighty litres is going to be reabsorbed <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.6"/> relatively under no control whatsoever <pause dur="0.3"/> you only have control over the small proportion the sort of ten per cent that actually gets to <kinesic desc="indicates point on slide" iterated="n"/> this part of the nephron <pause dur="1.9"/><kinesic desc="changes slide" iterated="n"/> so how does the # collecting duct regulate water reabsorption <pause dur="1.5"/> so it's regulated by this hormone you're going to see it called two things it's antidiuretic hormone hence it's A-D-H <pause dur="0.5"/> it's also called vasopressin and the abbreviation's A-V-P <pause dur="0.3"/> that's simply 'cause we've got an arginine in the human form of vasopressin <pause dur="0.8"/> and depending on the age of the textbook or

the age of the clinician they might alternate between A-V-P or A-D-H so you need to know both of them <pause dur="2.0"/> and the water transport in the collecting duct is also passive <pause dur="0.6"/> so if it's passive you need water channels you need something physically for the water to move through <pause dur="0.7"/> so in response to antidiuretic hormone so <pause dur="0.3"/> antidiuretic it's going to stop you peeing it's going to make you conserve water <pause dur="0.5"/> you get water channels # transported into the # <pause dur="0.6"/> <trunc>ch</trunc> # the cells of the the membrane of the tubule cells <pause dur="0.6"/> and we'll see exactly how <pause dur="0.2"/> in a <pause dur="0.2"/> bit later <pause dur="0.9"/> but you also need something else water's not going to move on its own <pause dur="0.5"/> you need an osmotic gradient <pause dur="0.4"/> so you need there to be a difference in the concentration of the <pause dur="0.4"/> # solutes in the filtrate <pause dur="0.4"/> compared to the concentration of solutes in the interstitial # <pause dur="0.4"/> tissues surrounding the nephron <pause dur="0.7"/> so you need to produce it <pause dur="0.5"/> so you have there's two things you have to have you have to have a very dilute urine <pause dur="0.4"/>

going into the collecting duct <pause dur="0.7"/> and you need to have this osmotic gradient which is produced by the counter current system <pause dur="0.5"/> and i've just put down here A-D-H also activates the urea <pause dur="0.2"/> # transporter <pause dur="0.4"/> and you'll see why that has a slight relevance later but don't get tied up on that <pause dur="1.9"/><kinesic desc="changes slide" iterated="n"/> so if we have a look at these water channels first we're going to take our <pause dur="0.2"/> <trunc>s</trunc> ways through we're going to look first at the water transport and antidiuretic hormone <pause dur="0.4"/> and then we're going to look at the generation of the osmotic gradient <pause dur="0.5"/> so it's at least five of them at the moment <pause dur="0.5"/> four of them are in the kidney <pause dur="0.6"/> # <pause dur="0.4"/> the <pause dur="0.2"/> the type one <pause dur="0.3"/> is in the proximal tubule <pause dur="0.3"/> and in the loop of Henle and this is what <pause dur="0.2"/> # <pause dur="0.2"/> is involved in the unregulated water transport it simply flows through the A-Q <pause dur="0.3"/> A-P-Q-one <pause dur="1.2"/> # three and four are also in the collecting duct <pause dur="0.4"/> # but these are in the basolateral membrane so that's the <pause dur="0.2"/> interstitial tissue <pause dur="0.2"/> # <pause dur="0.9"/> border with the tubule lumen remember <pause dur="0.3"/> you've got a kidney tubule cell water has to go into it <pause dur="0.4"/> and

out of it <pause dur="0.5"/> so these ones <kinesic desc="indicates point on slide" iterated="n"/> here are actually the # <pause dur="0.3"/> aquaporins that control the water release from the tubule cells back into the circulation <pause dur="0.9"/> and <kinesic desc="indicates point on slide" iterated="n"/> these are the ones we're interested in <pause dur="0.4"/> the aquaporins two <pause dur="0.4"/> and these are the aquaporins that go into the lumenal membranes that's the side where the filtrate is <pause dur="0.4"/> and they control the loss of water or <pause dur="0.5"/> # from the filtrate <pause dur="0.4"/> into the # eventually into the bloodstream <pause dur="0.8"/> so it's the A-P-Q-twos we're talking about today <pause dur="1.5"/><kinesic desc="changes slide" iterated="n"/> so what's antidiuretic hormone <pause dur="3.4"/> it's a very small peptide <pause dur="0.7"/> # <pause dur="0.3"/> and in terms of i've i've put down here details <pause dur="0.5"/> but for your interest <pause dur="0.2"/> it's made in the hypothalamus <pause dur="0.5"/> and it's released from the pituitary so you've got the hypothalamus and the pituitary involved one makes it <pause dur="0.3"/> and one releases it <pause dur="0.4"/> and that's important <pause dur="0.4"/> and it's got a very short half-life with most of these peptide hormones you expect them to have a very short half-life so the control's quite fine <pause dur="1.9"/><kinesic desc="changes slide" iterated="n"/> so how do we control its release <pause dur="1.0"/> the main mechanism by regulating A-D-H

release <pause dur="0.4"/> is in the hypothalamus <pause dur="0.4"/> and it has osmoreceptors up <kinesic desc="indicates point on slide" iterated="n"/> here which detect changes in plasma osmolarity <pause dur="0.9"/> so if the plasma osmolarity goes up that means it becomes more concentrated <pause dur="0.4"/> you want to dilute your plasma so you want to retain water <pause dur="0.5"/> you actually release A-D-H from the pituitary <pause dur="0.6"/> and this will then have the effect on the kidney <pause dur="1.0"/><kinesic desc="changes slide" iterated="n"/> # <pause dur="0.3"/> you can see here you've also got this is # <pause dur="0.2"/> obviously a diagram taken from the textbook you've got a thirst centre up here <pause dur="0.3"/> so the osmoreceptors not only control A-D-H release which is what we're looking at today <pause dur="0.3"/> but they also regulate your thirst <pause dur="0.3"/> so you've got the two aspects if you become water depleted or your plasma osmolarity goes up <pause dur="0.4"/> you release A-D-H to regulate water reabsorption <pause dur="0.3"/> or stop its loss from the kidney <pause dur="0.5"/> but you also stimulate your thirst reflex so you drink more so you're putting more fluid in as well <pause dur="1.0"/> # <pause dur="0.2"/> there's also i'm not going to dwell on it and i don't know whether you covered it in cardiovascular #

module but the heart also has stretch receptors in the right atrium <pause dur="0.4"/> and they respond to blood volume and they can also release A-D-H so that <pause dur="0.5"/> if you've got a large blood volume <pause dur="0.2"/> so you want to lose some water they switch off A-D-H synthesis <pause dur="0.3"/> or release and vice versa <pause dur="0.5"/> # but that's not part of <pause dur="0.2"/> this module <pause dur="1.5"/> so what happens with A-D-H release then so remember i said you want to keep your plasma osmolarity at about two-hundred-and-eighty <pause dur="0.5"/> so you can see here <pause dur="0.3"/> just above two-hundred-and-eighty <pause dur="0.3"/> you suddenly see this # increase in <pause dur="0.4"/> # A-D-H release <pause dur="0.4"/> and this is actually what we've normally got because our plasma osmolarity varies between about two-hundred-and-eighty and <pause dur="0.7"/> three-hundred if it has to it doesn't it's happier nearer to two-hundred-and-eighty <pause dur="0.4"/> we actually always have some A-D-H circulating you would expect to find A-D-H in normal people <pause dur="0.4"/> but you can see <pause dur="0.4"/> as it goes up and this isn't a very big difference remember your urine osmolarity can go up to twelve-hundred so this

is <pause dur="0.4"/> up to three-hundred-and-ten is actually a relatively small change <pause dur="0.4"/> you get # # a rapid increase in A-D-H release <pause dur="1.8"/><kinesic desc="changes slide" iterated="n"/> so how does it work <pause dur="0.5"/> so here's your # <pause dur="0.4"/> tubule # # cell of the collecting duct <pause dur="0.4"/> so <kinesic desc="indicates point on slide" iterated="n"/> this side is the lumen so this is where the urine is now in the collecting duct <pause dur="0.4"/> and <kinesic desc="indicates point on slide" iterated="n"/> this is the blood side <pause dur="0.6"/> but remember when talking about blood it actually goes out of the tubule cell <pause dur="0.3"/> into the interstitial fluid and then into the blood # <pause dur="0.3"/> vessel <pause dur="0.4"/> and that'll become <pause dur="0.2"/> even more apparent as we go through today <pause dur="0.8"/> so you've got vasopressin receptors on the # cell surface <pause dur="0.8"/> obviously they pick up # circulating levels of A-D-H <pause dur="0.6"/> and i've just put down here these are V-two receptors <pause dur="0.4"/> A-D-H also is a vasoconstrictor <pause dur="0.6"/> in which case it acts via V-one receptors to modulate # vasoconstrictions primarily in the skin <pause dur="0.4"/> but in other parts of the # body as well <pause dur="0.5"/> and if it's acting as a vasoconstrictor it uses V-one type receptors <pause dur="0.7"/> and they signal <trunc>fi</trunc> through phospholipase C <pause dur="1.1"/> whereas these V-two

receptors which are in the kidney <pause dur="0.4"/> # <pause dur="0.2"/> as we'll see now signal via cyclic A-M-P <pause dur="0.7"/> and they also have # <pause dur="0.4"/> a lower level of # <pause dur="0.8"/> you need less A-D-H for the V-two receptors to respond than you do for the V-one receptors so they're more sensitive <pause dur="1.6"/> so here you go so <pause dur="0.4"/> the A-D-H binds to the receptors cyclic A-M-P release <pause dur="0.4"/> <trunc>pro</trunc> # <pause dur="0.4"/> P-K-C activation and protein phosphorylation that's <trunc>ec</trunc> your standard # <pause dur="0.7"/> activation pathway <pause dur="1.2"/> what the protein phosphorylation does <pause dur="0.3"/> is it then allows these <pause dur="0.3"/> inactive water channels # aquaporins <pause dur="0.3"/> to be translocated to the membrane <pause dur="1.6"/> once they're inserted in the membrane this then allows water to move from the urine <pause dur="0.6"/> into the cell <pause dur="0.7"/> and you notice i'm actually talking about urine now because it's into the collecting system so it's urine <pause dur="0.3"/> not filtrate so we're actually concentrating our urine <pause dur="0.3"/> we're not concentrating our filtrate <pause dur="0.7"/> so the water moves in <pause dur="0.8"/> protein phosphorylation also longer term <pause dur="0.3"/> regulates the # transcription of the aquaporin gene <pause dur="0.4"/> so # if you

have continued stimulation here you'll get aquaporin synthesis which again then allows more <pause dur="0.4"/> # water transport to occur <pause dur="2.7"/><kinesic desc="changes slide" iterated="n"/> and if we look at what happens to the # permeability of the tubules <pause dur="0.4"/> so you can see <kinesic desc="indicates point on slide" iterated="n"/> here remember i said the proximal <pause dur="0.4"/> # tubule and we've got it split <kinesic desc="indicates point on slide" iterated="n"/> here into two the proximal convoluted and the proximal straight <pause dur="0.6"/> and the thin descending loop of Henle <pause dur="0.4"/> they've got a huge capacity to # reabsorb water passively by osmosis <pause dur="0.5"/> whereas <kinesic desc="indicates point on slide" iterated="n"/> these regions so you've got the thin <pause dur="0.2"/> ascending loop and the thick ascending loop <pause dur="0.4"/> and parts of the distal nephron and the collecting system <pause dur="0.3"/><kinesic desc="indicates point on slide" iterated="n"/> this is the cortical collecting duct <pause dur="0.5"/> # are able to absorb small amounts of water whereas the inner medullary collecting duct <pause dur="0.4"/> has no water absorption normally <pause dur="0.6"/> but under the control of A-V-P <pause dur="0.3"/> you can see both of these two <pause dur="0.7"/> # collecting duct regions # <pause dur="0.5"/> the ability to reabsorb water increases dramatically <pause dur="3.1"/><kinesic desc="changes slide" iterated="n"/> so what stimulates its release i know i said # you've got osmoreceptors that #

detect changes in plasma osmolarity and that's what actually stimulates the release of it <pause dur="0.5"/> but what do <pause dur="0.4"/> # <pause dur="0.2"/> what's actually detected so you've got changes here of plasma osmolarity <pause dur="0.8"/> if you get alterations in your extracellular volume <pause dur="0.5"/> therefore you're becoming dehydrated that will also # <pause dur="0.5"/> change its # <pause dur="0.4"/> release so in this case if you become dehydrated <pause dur="0.3"/> you want to retain water <pause dur="0.3"/> so you produce A-D-H which stops water secretion <pause dur="0.6"/> thirst <pause dur="0.5"/> nausea's quite interesting if you feel sick you start producing A-D-H because your body assumes if you feel sick you're going to be sick <pause dur="0.3"/> and if you are sick <pause dur="0.3"/> you lose water and lose # <pause dur="0.3"/> fluid volume from you so it kind of # <pause dur="0.4"/> as a precaution <pause dur="0.4"/> and also some drugs <pause dur="0.4"/> down here <pause dur="0.9"/> so you kind of might need to be aware of people if they're taking certain types of drugs and they come in with an abnormal fluid volume <pause dur="0.4"/> that might be why <pause dur="0.8"/><kinesic desc="changes slide" iterated="n"/> so if we look at inhibition of its release which will cause a fluid loss because you're not # causing reabsorption <pause dur="1.2"/> again <pause dur="0.3"/>

plasma osmolarity <pause dur="0.5"/> and then one we all know about alcohol <pause dur="0.5"/> drink too much alcohol you have to go to the loo constantly <pause dur="0.7"/> and # <pause dur="0.6"/> happens a lot particularly to boys with pints i have to say <pause dur="0.3"/> and the cold as well you go out in the cold weather you end up peeing more than normal or you want to <pause dur="0.3"/> and stress will have an effect so they're they're the # <pause dur="0.7"/> # <pause dur="0.6"/> physiological stimuli that actually alter <pause dur="0.3"/> A-D-H release <pause dur="1.4"/><kinesic desc="changes slide" iterated="n"/> okay so we've looked at the # <pause dur="0.2"/> insertion of water channels into the tubular membrane under the control of A-D-H <pause dur="0.4"/> what about the concentration of an osmotic gradient <pause dur="1.0"/> so if we look here so this is like a cross section you've got cortex outer medulla <pause dur="0.5"/> inner medulla <pause dur="0.4"/> and you can see if you look at sodium and chloride they're almost the same <pause dur="0.4"/> but they go up so there's much higher concentrations in the medulla than in the cortex <pause dur="0.4"/> and urea goes up <pause dur="0.5"/> and it's these three the combination of these three sodium chloride and urea <pause dur="0.4"/> that actually makes the inner medulla of the <trunc>cor</trunc> of the kidney <pause dur="0.4"/> very

concentrated osmoticallywise <pause dur="0.3"/> so that's what generates an osmotic difference <pause dur="0.6"/><kinesic desc="changes slide" iterated="n"/> so how do we do this <pause dur="3.9"/><kinesic desc="changes slide" iterated="n"/> so there's a number of mechanisms if we look at urea first <pause dur="1.4"/> now remember urea's freely filtered <pause dur="0.4"/> so everything that's circulating would potentially be filtered so that's a hundred per cent goes into the # <pause dur="0.5"/> nephron <pause dur="1.3"/> of that fifty per cent is reabsorbed early on in the proximal tubule so you've got fifty per cent of your <pause dur="0.3"/> total urea concentration going into the nephron down here <pause dur="2.1"/> when that goes it goes all the way round gets right round to the collecting duct <pause dur="0.4"/> and it's reabsorbed so <pause dur="0.4"/> # <pause dur="1.0"/> and you've got seventy per cent of that remaining fifty per cent so the seventy per cent here is reabsorbed <pause dur="0.2"/> goes into the medulla <pause dur="0.5"/> because you remember this is all interstitial space between these parts of the nephron <pause dur="0.9"/> but some of that is then secreted back into the kidney so if you remember urea's one of those strange substances <pause dur="0.4"/> it's filtered <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.5"/> it's reabsorbed <kinesic desc="indicates point on slide" iterated="n"/> here and <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.3"/> and it's also

secreted so you've got <trunc>b</trunc> all three of the main mechanisms of # <pause dur="0.5"/> urine production going on with urea <pause dur="0.9"/> so of this seventy per cent that it secretes into the medulla <pause dur="0.4"/> some of that is then taken back up into the nephron <pause dur="0.7"/> and sixty per cent <pause dur="0.5"/> so you can see you've got ten per cent difference between what you reabsorb and what you put back into the nephron <pause dur="0.6"/> and that ten per cent <pause dur="0.3"/> stays in the medulla <pause dur="0.5"/> and because # and it creates # a concentration gradient so you'll have less urea at <kinesic desc="indicates point on slide" iterated="n"/> this region <pause dur="0.3"/> and more urea <kinesic desc="indicates point on slide" iterated="n"/> down here and you can see <pause dur="0.4"/> # <pause dur="0.5"/> you get ten per cent in your <pause dur="0.2"/> # <pause dur="0.4"/> medulla <pause dur="0.2"/> you retain that <pause dur="0.2"/> that's part of your osmotic concentration gradient <pause dur="0.7"/> and then that actually means if you do the sums that forty per cent of your filtered load actually ends up being excreted by the kidneys <pause dur="0.5"/> but it's <kinesic desc="indicates point on slide" iterated="n"/> this small percentage here that remains in the medulla <pause dur="0.6"/> that's important <pause dur="2.5"/><kinesic desc="changes slide" iterated="n"/> okay <pause dur="0.4"/> loop of Henle did you all do this at A-level <pause dur="1.7"/> no <pause dur="0.4"/> yes <pause dur="0.8"/> did you understand it <pause dur="2.2"/> <vocal desc="laughter" iterated="y" n="ss" dur="2"/><vocal desc="laugh" iterated="n"/> <pause dur="0.3"/>

i think that's probably a pretty mixed response <pause dur="0.7"/> hopefully you will <vocal desc="laughter" iterated="y" n="ss" dur="1"/> at the end of this <pause dur="0.2"/> can't guarantee it there's always books or you can come and ask me <pause dur="0.7"/> but hopefully i'll take you through it <pause dur="1.8"/> now this is absolutely vital without a loop of Henle <pause dur="0.3"/> we would not be able to concentrate our urine <pause dur="0.3"/> we'd be peeing out as much as we <trunc>m</trunc> # <pause dur="0.3"/> we filter <pause dur="1.1"/> now it's only present in birds and mammals <pause dur="0.6"/> so we're the only # species <pause dur="0.2"/> # birds and mammals that are able to actually concentrate their urine anything else <pause dur="0.4"/> what they filter is what they pass as urine <pause dur="0.9"/> and that's because we have loops of Henle <pause dur="1.3"/><kinesic desc="changes slide" iterated="n"/> so if we didn't do anything <pause dur="0.2"/> here's your isotonic urine 'cause you remember your filtrate's isotonic to your plasma so it's going to come in at two-hundred-and-eighty <pause dur="0.3"/> three-hundred <trunc>millimol</trunc> milliosmoles <pause dur="0.5"/> and that's a hundred-and-eighty litres a day <pause dur="0.3"/> so if we didn't concentrate it at all <pause dur="0.3"/> we'd lose a hundred-and-eighty litres a day which is about seven-point-five litres an hour <pause dur="0.3"/> you'd be

sitting on the loo constantly <pause dur="0.6"/> apart from the fact you couldn't drink enough to replace all the water you were losing <pause dur="1.7"/><kinesic desc="changes slide" iterated="n"/> so you have to split the loop of Henle into three sections for this to work <pause dur="0.9"/> and this is <pause dur="0.2"/> this is what the <trunc>c</trunc> sections <trunc>consid</trunc> # together actually do but don't worry about that <pause dur="0.5"/> so you have the thin <pause dur="0.6"/> descending loop <pause dur="0.9"/> and this is permeable to water <pause dur="0.7"/> and slightly permeable to sodium and chloride but it's the permeability to water that's important <pause dur="1.1"/> if we look at the # <pause dur="0.3"/> thin ascending loop <pause dur="0.8"/> it's impermeable to water and there's a little bit of salt and water transport here as well <pause dur="0.4"/> # <trunc>s</trunc> # sorry <pause dur="0.3"/> sodium chloride transport <pause dur="1.2"/> but the thick ascending loop is what's important as well <pause dur="0.6"/> you can see here it has sodium and chloride reabsorption but it's completely impermeable to water <pause dur="0.7"/> so you have to remember <kinesic desc="indicates point on slide" iterated="n"/> this side is permeable to water <pause dur="0.9"/><kinesic desc="indicates point on slide" iterated="n"/> this part isn't <pause dur="0.7"/> but <kinesic desc="indicates point on slide" iterated="n"/>this part transports your sodium and your chloride <pause dur="1.3"/> so if we have a look so this is basically <pause dur="0.2"/> reiterates what i've said <pause dur="0.3"/> so

there's your water transport and if you take a section here <pause dur="0.7"/><kinesic desc="indicates point on slide" iterated="n"/> you can see so this is the lumen so this is the side where the filtrate is <pause dur="0.5"/> and that has that takes up <pause dur="0.4"/> it's got the sodium # <pause dur="0.4"/> the potassium-two-chloride sodium pump <pause dur="0.4"/> which takes up <pause dur="0.6"/> # all of these ions <pause dur="0.4"/> the energy for that comes from the sodium potassium A-T-P-ase <pause dur="0.7"/> but the net effect of this is that it transports sodium out <pause dur="0.8"/> and chloride goes out through <kinesic desc="indicates point on slide" iterated="n"/> this channel <pause dur="0.7"/> so you take up <pause dur="0.2"/> # sodium and chloride <pause dur="0.4"/> from the # filtrate <pause dur="0.4"/> and you put it into the interstitial <pause dur="0.5"/> tissue surrounding the nephron <pause dur="1.3"/> okay <pause dur="0.6"/><kinesic desc="changes slide" iterated="n"/> so this is the counter current mechanism so this is <pause dur="0.2"/> this is your loop of Henle <pause dur="0.2"/> thin bits <pause dur="0.3"/><kinesic desc="changes slide" iterated="n"/> thick bits <pause dur="1.1"/><kinesic desc="changes slide" iterated="n"/> and the numbers kind of refer to the osmolarity but don't get tied up with specific numbers it's just to illustrate something nobody's ever going to ask you what <pause dur="0.4"/> what the number <kinesic desc="indicates point on slide" iterated="n"/> down here should be or what the number up <kinesic desc="indicates point on slide" iterated="n"/> there should be <pause dur="1.5"/> so you have to remember <pause dur="1.0"/><kinesic desc="indicates point on slide" iterated="n"/> this part <pause dur="0.3"/> is permeable to water <pause dur="0.8"/> # <kinesic desc="indicates point on slide" iterated="n"/> this part isn't permeable to

water <pause dur="0.3"/> but has sodium pumps <pause dur="0.3"/> okay <pause dur="0.8"/> so this is what would happen if nothing happened <pause dur="0.3"/> you've got if i just go back one minute <pause dur="0.4"/><kinesic desc="changes slide" iterated="n"/> if nothing happened here this is water coming in <pause dur="0.3"/> and you have to also imagine this is static urine obviously the urine's flowing through your nephron continuously <pause dur="0.3"/> but you have to take snapshots at it to imagine how the system works <pause dur="0.4"/> so if nothing happened <pause dur="0.5"/> three-hundred milliosmoles in <pause dur="0.2"/> i know it should be two-hundred-and-eighty but it's much neater to use three-hundred for illustration purposes <pause dur="0.5"/> so <kinesic desc="indicates point on slide" iterated="n"/> this is isotonic filtrate coming in <pause dur="0.5"/> and if nothing happened whatsoever you'd have isotonic filtrate going out <pause dur="1.5"/><kinesic desc="changes slide" iterated="n"/> flick through those <pause dur="0.8"/> okay <pause dur="1.2"/> so this is what happens <unclear>those</unclear> the sodium pumps in <kinesic desc="indicates point on slide" iterated="n"/> this part of the # loop of Henle switch on <pause dur="0.4"/> and they pump sodium chloride <pause dur="0.3"/> out into the medulla <pause dur="0.7"/> and what they do their aim is to keep a two-hundred milliosmole difference between the filtrate coming round <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.4"/> and the concentration in the medulla <pause dur="0.7"/> so they <trunc>s</trunc>

they switch on these pumps <pause dur="0.3"/> so the medulla becomes concentrated <pause dur="0.3"/> compared to the filtrate that's in the loop of Henle <pause dur="1.2"/> now if you remember <pause dur="0.5"/><kinesic desc="changes slide" iterated="n"/><kinesic desc="indicates point on slide" iterated="n"/> this part of the loop of Henle is permeable to water <pause dur="0.8"/> so <pause dur="0.3"/> at the moment in this situation you have <pause dur="0.3"/> dilute <pause dur="0.3"/> filtrate <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.4"/> compared to the interstitial <trunc>flui</trunc> fluid concentration <pause dur="0.6"/> so water flows from <pause dur="0.5"/> a high concentration of water <pause dur="0.4"/> into a lower concentration to try and equal it out <pause dur="0.3"/> so water will flow <pause dur="0.4"/> from here <pause dur="0.5"/><kinesic desc="indicates point on slide" iterated="n"/> into there <pause dur="0.4"/><kinesic desc="indicates point on slide" iterated="n"/> which will make <kinesic desc="indicates point on slide" iterated="n"/> this more concentrated <pause dur="0.8"/> is that clear <pause dur="0.3"/> which is what happens here <pause dur="0.5"/><kinesic desc="indicates point on slide" iterated="n"/> so then you end up with sort of one cycle of urine moving round <pause dur="0.4"/> you've got <pause dur="0.3"/> dilute urine <kinesic desc="indicates point on slide" iterated="n"/> here compared to <kinesic desc="indicates point on slide" iterated="n"/> this part of the loop of Henle <pause dur="0.6"/> and <pause dur="0.2"/> compared to when we started <kinesic desc="indicates point on slide" iterated="n"/> here where it would have been three-hundred you've now got a <trunc>t</trunc> # <pause dur="0.7"/> increased concentration in the medulla <pause dur="0.9"/><kinesic desc="changes slide" iterated="n"/> so if we move on one more time the urine moves round a bit more so you've still got three-hundred coming in but if you remember it was two-hundred here <pause dur="2.4"/> pumps pump <pause dur="0.6"/>

sodium out so that you get a two-hundred # <pause dur="0.2"/> milliosmole difference <pause dur="0.7"/><kinesic desc="indicates point on slide" iterated="n"/> this part of the nephron says hang on a minute i'm too <trunc>conc</trunc> i'm too dilute now compared to the medulla <pause dur="0.3"/> and water moves from that thin ascending # descending loop <pause dur="0.5"/> into the medulla <pause dur="0.2"/> to equalize it so again <pause dur="0.6"/> the concentration in the thin descending loop <pause dur="0.4"/> equals that in the medulla <pause dur="0.6"/> whereas the thick ascending loop <pause dur="0.5"/> is a two-hundred milliosmole difference making this urine <pause dur="0.3"/> or this filtrate more dilute <pause dur="0.7"/> and that's it that's all that happens <pause dur="0.7"/> the consequences of this are <pause dur="0.5"/> that filtrate coming in <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.3"/> is isoosmotic to your plasma <pause dur="0.3"/> so two-hundred-and-eighty <pause dur="1.1"/> by the time it gets down <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.4"/> your filtrate # <pause dur="0.3"/> has become more concentrated because it's losing water all the way down <kinesic desc="indicates point on slide" iterated="n"/> here to try and equalize the difference between the medulla <pause dur="0.4"/> and the filtrate osmolarity <pause dur="0.6"/> and then when it goes up here <kinesic desc="indicates point on slide" iterated="n"/><pause dur="0.2"/> salt is pumped out which means you have dilute urine <pause dur="0.5"/> <trunc>c</trunc> # filtrate coming out <pause dur="0.5"/> so you have a difference at the top

<trunc>wi</trunc> compared to filtrate in <pause dur="0.4"/> and filtrate out it's more dilute <pause dur="1.3"/> is that all clear <pause dur="0.7"/> anybody want me to go over it again <pause dur="2.1"/> okay <pause dur="0.4"/> i'll take your silence as that's all right and <pause dur="0.4"/> if you don't understand it ask me later <pause dur="1.1"/> okay so we've now developed <pause dur="0.4"/> what we've got now is we've got lots of solutes in the medulla <pause dur="0.4"/> and they get more and more concentrated <pause dur="0.2"/> the nearer the # <pause dur="0.3"/> tip of the medulla that you get to <pause dur="0.9"/> now if you had normal blood flow if you had simply # a straight blood vessel <pause dur="0.4"/> going from the cortex through the medulla <pause dur="0.4"/> and into the sort of collecting region the the pelvis or the kidney <pause dur="0.6"/> it's going to wash all those solutes out because # <pause dur="0.4"/> the water in the solute concentration is simply going to # <pause dur="0.2"/> # equalize as the blood vessel <trunc>go</trunc> travels down through the medulla <pause dur="0.3"/> and all that hard work by the loop of Henle is completely obliviated <pause dur="0.4"/> or alleviated <pause dur="1.1"/> so remember the blood system's set up differently in the kidney from what you'd normally expect <pause dur="1.4"/><kinesic desc="changes slide" iterated="n"/> so we have the <pause dur="0.2"/> vasa recta remember i mentioned this right

back in the first # <pause dur="0.2"/> microstructure lecture <pause dur="0.5"/> and these are very specialized blood vessels <pause dur="0.3"/> and they parallel the # loops of Henle <pause dur="1.2"/> and they've got very low blood <trunc>f</trunc> # flow if you remember i mentioned that although the kidney has <pause dur="0.3"/> an extremely high blood flow for the size of the organ <pause dur="0.6"/> you only get five <trunc>per</trunc> <pause dur="0.2"/> to ten per cent of this actually going into the medulla so that's one of the way they conserve this osmotic gradient <pause dur="0.3"/> is not to put too much blood in the medulla and it's set just <trunc>i</trunc> <trunc>un</trunc> <pause dur="0.4"/> # a high enough flow rate so that you can deliver the nutrients and remove what you have to from the medulla <pause dur="0.7"/> and they're also in this hairpin arrangement <pause dur="1.0"/><kinesic desc="changes slide" iterated="n"/> so just to remind you they look like this <pause dur="0.4"/> so you remember you have these # <pause dur="0.5"/> bigger vessels coming in <pause dur="0.4"/> and this is the # a medullary <trunc>pyla</trunc> pyramid <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.5"/> so the blood vessels come in and they kind of go along <pause dur="0.4"/> the cortex-medulla <pause dur="0.3"/> border <pause dur="0.6"/> and then you get these loops <pause dur="0.2"/> branching off the vasa recta which follow round <pause dur="0.4"/> the long loops of Henle <pause dur="0.6"/>

remember some of the # nephrons have long loops and some have short loops <pause dur="0.4"/> # when we're talking about concentration of urine <pause dur="0.3"/> it's the <trunc>juxta</trunc> # medullary nephrons that are important they're the ones with the very long loops of Henle <pause dur="0.5"/> and they have these blood vessels that parallel them <pause dur="0.3"/> around <pause dur="1.7"/><kinesic desc="changes slide" iterated="n"/> so this is how the vasa recta works <pause dur="0.3"/> now remember this is slightly different from the # <pause dur="0.2"/> nephron <pause dur="0.4"/> because this is a capillary <pause dur="0.4"/> so it's semi-permeable <pause dur="0.2"/> and doesn't have the pumps and the impermeability to water that the nephron has so this is a semi-permeable membrane now <pause dur="0.5"/> permeable to both solutes and water <pause dur="0.9"/> so here we have <pause dur="0.3"/> <kinesic desc="indicates point on slide" iterated="n"/> this is the cortex this is the blood coming in <pause dur="0.4"/> at # isoosmotic to your filtrate <pause dur="0.2"/> at this stage <pause dur="0.6"/> and but remember in the medulla we've now built up this concentration gradient so it's dilute at the tip <pause dur="0.5"/> and more concentrated at the bottom <pause dur="0.8"/> and as the # blood flows in down <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.5"/> what happens is that <pause dur="0.4"/> from the # <pause dur="0.4"/> dilute <pause dur="0.3"/> filtrate you lose water because <pause dur="0.3"/>

it's simple diffusion the water wants to try and equate the balance and <pause dur="0.5"/> it's effectively <pause dur="0.4"/> concentrated water in the filtrate so it flows to a region of low water concentration so it flows <pause dur="0.3"/> out of dilute filtrate <pause dur="0.4"/> into concentrated medulla <pause dur="0.6"/> and likewise the solutes do the opposite there's lots of solutes <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.4"/> not so many <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.2"/> so to try and # equilibrate that solutes move in <pause dur="0.6"/> now this is what i was saying if it was a straight # <pause dur="0.6"/> capillary that then just went on out down <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.5"/> all you've done is negate <kinesic desc="indicates point on slide" iterated="n"/> this # concentration gradient you've built up <pause dur="1.1"/> but it's again it's arranged like # <pause dur="0.9"/> the loop <trunc>o</trunc> the loop of Henle is and its counter current system <pause dur="0.4"/><kinesic desc="changes slide" iterated="n"/> so this is what would happen <pause dur="0.4"/> so it becomes more <trunc>concentra</trunc> your blood becomes more concentrated in here <kinesic desc="indicates point on slide" iterated="n"/> as it flows down to the tip of the hairpin <pause dur="0.4"/> and somewhere round <kinesic desc="indicates point on slide" iterated="n"/> here it <trunc>reach</trunc> <trunc>equi</trunc> # a point of <trunc>equili</trunc> # equilibration between the <pause dur="0.4"/> concentration in the blood and the concentration in the medulla <pause dur="1.1"/> but as it then flows back up <pause dur="0.4"/>

it's going up through a more dilute system <pause dur="0.5"/> and <pause dur="0.4"/> exactly the same happens <kinesic desc="indicates point on slide" iterated="n"/> here in terms of the solutes and the waters try to compensate and equal things out but they go in the opposite direction <pause dur="0.6"/> so here <kinesic desc="indicates point on slide" iterated="n"/> <pause dur="0.4"/> you've got more solute than you have in the medulla so the solutes go out back into the medulla <pause dur="0.5"/> and likewise <pause dur="0.3"/> the water from the medulla <pause dur="0.2"/> flows in to try and compensate <pause dur="0.5"/> so the net effect <kinesic desc="indicates point on slide" iterated="n"/> here is that although you <trunc>l</trunc> lose water <kinesic desc="indicates point on slide" iterated="n"/> here and gain solutes which is what you don't want <pause dur="0.5"/> because it's a hairpin and goes back up again <pause dur="0.3"/> the opposite happens on this <kinesic desc="indicates point on slide" iterated="n"/> # <pause dur="0.9"/> # # <pause dur="0.2"/> this direction <pause dur="0.5"/> and you actually end up <pause dur="0.3"/> with just a small difference between your <pause dur="0.3"/> concentration of your blood going in and the concentration of your blood <trunc>le</trunc> <pause dur="0.3"/> leaving <pause dur="0.3"/> and that maintains <pause dur="0.3"/> the concentration gradient in the medulla <pause dur="1.0"/> it also does one really other important things 'cause if you remember from stones urea <pause dur="0.4"/> and sodium and chloride they're all things

that can crystallize out <pause dur="0.6"/> so if you had a lot of urea <pause dur="0.5"/> and sodium and chloride just sitting in your medulla doing nothing statically they'd crystallize and form # <pause dur="0.2"/> crystals in the medulla <pause dur="0.4"/> and stop it working properly <pause dur="0.9"/> if you imagine you've got a loop of Henle <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.3"/> and you've got urea going into this space and then <pause dur="0.2"/> into <kinesic desc="indicates point on slide" iterated="n"/> here and then out again it kind of keeps the circulation system going between the nephron and the blood system and the medulla <pause dur="0.4"/> and that circulation prevents any precipitation occurring of the salts that you've got in the medulla <pause dur="0.5"/> because this is quite a high <pause dur="0.3"/> you're talking of twelve fourteen-hundred <pause dur="0.4"/> # <trunc>conce</trunc> osmotic concentration <kinesic desc="indicates point on slide" iterated="n"/> here so that's quite concentrated <pause dur="0.6"/> and they would precipitate <pause dur="0.7"/><kinesic desc="changes slide" iterated="n"/> so here you go so this is what you end up with you've got a <pause dur="0.3"/> osmotic gradient as you go through the medulla <pause dur="0.9"/> and the thing that <trunc>a</trunc> then allows to happen <pause dur="1.2"/> you've got this osmotic gradient <kinesic desc="indicates point on slide" iterated="n"/> here and this is your collecting duct going through it <pause dur="0.6"/> A-D-H is being

stimulated to insert water channels <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.6"/> and because they work by osmosis <pause dur="0.4"/> the water can then flow from the collecting duct <pause dur="0.4"/> back into the medulla <pause dur="0.3"/> and that then obviously gets taken away <pause dur="0.4"/> # <pause dur="0.5"/> back into the blood supply and into the <trunc>sys</trunc> # body <pause dur="0.5"/> so that's how it works <pause dur="1.5"/> okay <pause dur="0.8"/> so that's the physiology <pause dur="1.0"/><kinesic desc="changes slide" iterated="n"/> what happens when it all goes wrong <pause dur="0.5"/> and you get some <pause dur="0.4"/> # diseased state <pause dur="0.4"/> well basically you're either going to make too dilute or too concentrated a urine <pause dur="0.4"/> that's all that happens <pause dur="1.4"/><kinesic desc="changes slide" iterated="n"/> so this is the first condition we're going to look at this is a syndrome of inappropriate secretion of A-D-H <pause dur="0.4"/> means you're secreting A-D-H when you shouldn't do <pause dur="0.7"/> it's an antidiuretic hormone it's going to stop you concentrating your urine <pause dur="0.3"/> so your blood volume is going to go up and you're <pause dur="0.2"/> going to become fluid overloaded <pause dur="0.9"/> so i've put up here this is normally what happens it's often <pause dur="0.4"/> # a pituitary tumour which is secreting A-D-H <pause dur="0.4"/> or you get them from # <pause dur="0.3"/> ectopic sites some <pause dur="0.5"/> cancer remember a lot of these tumours

a lot of cancers produce hormones they're not supposed to <pause dur="0.5"/> you get parathyroid hormone related peptide produced by <pause dur="0.4"/> # breast cancer <pause dur="0.2"/> # tumours of breast cancer origin <pause dur="0.4"/> again some of them produce A-D-H <pause dur="1.3"/> likewise sometimes you obviously if you have a pituitary tumour <pause dur="0.4"/> and that metastasizes <pause dur="0.2"/> it's the same cell type so that also would account for A-D-H being produced <pause dur="0.9"/> so what are the signs and symptoms <pause dur="0.5"/> remember i said you were going to get fluid <trunc>lo</trunc> overloaded but this is <pause dur="0.3"/> only regulating your water reabsorption <pause dur="0.2"/> doesn't affect your sodium <pause dur="0.7"/> so you become hyponatraemia <pause dur="0.6"/> # or <trunc>dis</trunc> you develop hyponatraemia <pause dur="0.3"/> so that's low sodium concentration in your blood <pause dur="0.7"/> and that's simply because the sodium has been diluted <pause dur="1.0"/> if you look at the total body sodium of these people it's exactly what you would expect it's normal <pause dur="0.5"/> but because they've retained more water <pause dur="0.3"/> you've diluted the sodium <pause dur="0.4"/> so when you send off <pause dur="0.9"/> i don't know ten mls or whatever to a lab and it

comes back as a <pause dur="0.4"/> molarity of your sodium concentration <pause dur="0.6"/> you're going to think their sodium is low <pause dur="1.4"/> now that has effect because low sodium will # <pause dur="0.6"/> have effects on your system's physiological systems and we do look at these # <pause dur="0.9"/> actually one of the case studies today is # <pause dur="0.5"/> she's got low sodium <pause dur="0.7"/> # <pause dur="0.7"/> but remember it's diluted <pause dur="0.2"/> your actual blood body sodium isn't low but you've diluted what you've got <pause dur="1.6"/> again <pause dur="0.5"/> # if you've got too much # <pause dur="0.5"/> A-D-H your urine's going to become too concentrated when you're not expecting it to become concentrated <pause dur="0.5"/> and again the sodium's going to be high in your urine so these are <trunc>s</trunc> kind of the classic symptoms <pause dur="0.3"/> the hyponatraemic <pause dur="0.6"/> the urine's concentrated <pause dur="0.2"/> and the urine sodium's quite high <pause dur="2.1"/><kinesic desc="changes slide" iterated="n"/> and what are the causes <pause dur="0.7"/> i've # i've listed them here <pause dur="0.5"/> # there's a range of things and i'll just take you through them but if you simply remember it's likely to be a tumour <pause dur="0.7"/> or an inflammatory response <pause dur="0.5"/> or drugs or stress that's kind of an easier way of remembering the causes

of <pause dur="0.5"/> # <pause dur="1.4"/> syndrome of # A-D-H release <pause dur="0.7"/> but if we look here <pause dur="0.4"/> obviously <pause dur="0.2"/> you make and release it from the pituitary and hypothalamus <pause dur="0.3"/> so any lesions in that region can have problems <pause dur="0.5"/> inflammatory diseases generally will cause A-D-H release or can do <pause dur="0.3"/> but obviously if they're in the brain that that's # more likely <pause dur="0.7"/> and there's a whole range of other things <pause dur="1.2"/> problems with the lungs also # <pause dur="0.2"/> tend to cause # A-D-H release <pause dur="0.4"/> C-O-P-D is a classic symptom where you get A-D-H release <pause dur="0.5"/> # and that makes it even worse because if they've got chronic obstructive # lung disease already <pause dur="0.3"/> the last thing you want to do is fluid overload these people and give their lungs even more of a fluid challenge so that exacerbates their problem <pause dur="0.6"/> and tumours and particularly the small cell type in in lungs are <pause dur="0.2"/> are bad <pause dur="1.1"/> and then also # <pause dur="0.4"/> certain drugs <pause dur="0.8"/> so okay they've got mixed action so i've put a whole load here <pause dur="0.3"/> there's far far far more drugs than i've listed here but these are <trunc>com</trunc> some of the common ones <pause dur="0.6"/>

oxytocin's important <pause dur="0.4"/> because that happens when you give oxytocin quite often to pregnant women if you're inducing labour <pause dur="0.4"/> and you have to bear in mind the effect that will have on their fluid system so <pause dur="0.4"/> sometimes you may be inducing labour because of pre-eclampsia the last thing you want to do <pause dur="0.3"/> by giving them oxytocin <pause dur="0.3"/> is to cause fluid retention as well so you have to be careful <pause dur="0.4"/> when you give oxytocin that the person's <pause dur="0.3"/> or monitor their fluid load <pause dur="0.4"/> # <pause dur="0.2"/> carefully <pause dur="0.6"/> # Ecstasy as well <pause dur="0.5"/> people who take Ecstasy have a problem with fluid # loss they tend to retain it and become very oedematous <pause dur="0.4"/> and that's acting probably via A-D-H <pause dur="0.6"/> and then just down here post-operatively <pause dur="0.5"/> obviously that's quite specialized but <pause dur="0.6"/> the case varies and this trauma would also go in there <pause dur="0.5"/> a sudden fluid loss may sometimes activate <pause dur="0.3"/> A-D-H <pause dur="0.3"/> now it may not because if you lose blood you're losing isoosmotic <pause dur="0.4"/> # fluid <pause dur="0.5"/> so you're not altering the ratio of # <pause dur="0.5"/> the plasma osmolarity you might be getting low plasma volume

but the osmolarity of it is normal <pause dur="1.0"/> the slight trouble you have sometimes post-operatively is if you give somebody glucose in the drip because glucose is metabolized very quickly to water and whatever's left over <pause dur="0.5"/> so sometimes by giving glucose <pause dur="0.4"/> you're # going to exacerbate the fluid overload <pause dur="0.3"/> that's already been caused by A-D-H release <pause dur="0.8"/> # <pause dur="0.4"/> and H-I-V people <pause dur="0.2"/> the people that are H-I-V positive they have <pause dur="0.2"/> problems about a third of them <pause dur="0.5"/> # produce # A-D-H <pause dur="0.7"/> so just bear that in mind <pause dur="1.4"/><kinesic desc="changes slide" iterated="n"/> so what's the consequences the basic consequences are you end up with too much water <pause dur="0.8"/> # so we've talked about having low plasma sodium <pause dur="0.5"/> sometimes you get oedema <pause dur="0.5"/> sometimes you don't because this fluid overload is primarily a circulatory problem <pause dur="0.5"/> so the fluid overload is still in the blood vessels and in your blood volume <pause dur="0.5"/> but obviously sometimes that has the knock-on effect of oedema <pause dur="0.7"/> so if somebody <pause dur="0.4"/> you suspect somebody of having <trunc>S-R</trunc> S-I-A-D-H <pause dur="0.5"/> and they haven't got oedema it doesn't rule it out but

they may have <pause dur="0.8"/> and i've just mentioned here that if your plasma sodium drops too low obviously you're then into problems and it can actually become an emergency that you have to deal with <pause dur="1.6"/><kinesic desc="changes slide" iterated="n"/> okay so that's if you have too much A-D-H so you retain fluid what happens if you have the opposite condition <pause dur="0.4"/> you can't concentrate your urine and you lose loads of water <pause dur="0.7"/> and this is called diabetes insipidus <pause dur="0.3"/> and this is why i keep stressing the importance when you answer a question <pause dur="0.8"/> particularly in this module but generally it's a habit you should get into you have to <pause dur="0.5"/> be careful that you tell me which <trunc>tal</trunc> <pause dur="0.2"/> type of diabetes you're going to be talking about because <pause dur="0.4"/> # diabetes mellitus has effects on the kidney <pause dur="0.6"/> # so i will be asking you questions about that and obviously diabetes insipidus so you have to tell me which diabetic condition you're you're talking about <pause dur="2.0"/><kinesic desc="changes slide" iterated="n"/> so there's two conditions so you basically have central <pause dur="0.3"/> or nephrogenic # <pause dur="0.5"/> diabetes insipidus <pause dur="1.0"/> and what they

refer to obviously <pause dur="0.5"/> nephrogenic is # a condition that refers to problems with the kidney <pause dur="0.5"/> and central <pause dur="0.3"/> # is a a condition it's a bit misleading it's nothing to do with central it's central as in your hypothalamus or your pituitary it's your central control system <pause dur="0.4"/> so if it's central it's a problem with the <pause dur="0.3"/> synthesis and release <pause dur="0.3"/> if it's nephrogenic it's a problem with the kidneys being able to respond <pause dur="1.1"/> so <kinesic desc="indicates point on slide" iterated="n"/> here <pause dur="0.2"/> symptoms are obvious polyurea <pause dur="0.4"/> they produce loads and loads of urine <pause dur="0.3"/> the consequences are they have to drink lots to try and compensate for this <pause dur="0.6"/> now remember these are symptoms of diabetes mellitus as well somebody comes in saying they're <pause dur="0.5"/> you know into your surgery if you're a G-P and says i'm drinking loads and i'm peeing loads you probably think they had diabetes mellitus or you'd want to test their urine for glucose <pause dur="0.8"/> but obviously if they're drinking lots and peeing lots <pause dur="0.3"/> no glucose in their urine <pause dur="0.3"/> you might start thinking about other forms <pause dur="0.5"/> and they're going

to have # <pause dur="0.7"/> a low <trunc>pa</trunc> a plasma <trunc>os</trunc> a low urine osmolarity because they're passing lots out <pause dur="2.2"/> okay so what's the defects so i've talked about this so <pause dur="0.2"/> central's a problem with the brain you either don't make it <pause dur="0.3"/> or you can't secrete it <pause dur="0.6"/> so the obvious cause is allow for something like trauma or injury or infection <pause dur="0.5"/> and inflammation that are going to affect your pituitary hypothalamic <pause dur="0.2"/> # function <pause dur="1.7"/> or nephrogenic now nephrogenic it simply means you you're producing A-D-H correctly <pause dur="0.3"/> as your body wants it <pause dur="0.4"/> but your <trunc>sa</trunc> your kidneys can't respond to it <pause dur="0.5"/> and there's a number of reasons for this they could be <pause dur="0.2"/> congenital there are people who have congenital problems <pause dur="0.4"/> but also an infection or an obstruction can do it <pause dur="0.7"/> you might lack the receptor <pause dur="0.4"/> # or you can't form or translocate aquaporins obviously this isn't something that tends to happen <pause dur="0.4"/> late in life this is a <pause dur="0.6"/> problem that will have been with you a congenital problem from birth <pause dur="1.5"/> # <pause dur="0.4"/> sometimes i've just put down here <pause dur="0.4"/> if it's a problem

with aquaporin translocation remember cyclic A-M-P is important in this <pause dur="0.3"/> so things that interfere with the cyclic A-M-P signalling pathway <pause dur="0.4"/> may well interfere with # A-D-H signalling <pause dur="0.3"/> and therefore interfere with # aquaporin translocation so <pause dur="0.3"/> if they're on drugs that you know might inhibit that kind of pathway <pause dur="0.4"/> that might # also be a cause of it <pause dur="1.9"/><kinesic desc="changes slide" iterated="n"/> so this is what you do you're going to want if you've got somebody you're pretty certain has got diabetes insipidus you're going to want to know which form they've got <pause dur="0.4"/> so you do what's called a water deprivation test <pause dur="0.8"/> so here we have along the bottom <pause dur="0.5"/> # <pause dur="0.2"/> or at least up the up the side here we've got # urine osmolarity <pause dur="0.6"/> and this is A-D-H concentration <pause dur="0.5"/> i'm sorry i've cut off the units i have no idea what A-D-H is actually measured in <pause dur="0.4"/> # but this is A-D-H along here <kinesic desc="indicates point on slide" iterated="n"/><pause dur="1.7"/> so # <pause dur="0.6"/> if somebody a normal person <pause dur="1.0"/> i'm sorry i'm telling you it's A-D-H i think i might be wrong now i think that could be hours <pause dur="1.6"/> sorry i can't remember it's # in the

textbook but ignore that 'cause it's totally irrelevant for the actual # <pause dur="0.6"/> what i'm going to tell you <pause dur="0.3"/> but <kinesic desc="indicates point on slide" iterated="n"/> this is a normal person here <pause dur="0.5"/> so <pause dur="0.3"/> as their A-D-H <pause dur="0.2"/> rises <pause dur="0.4"/> yeah it must be A-D-H as their A-D-H rises <pause dur="0.5"/> their urine osmolarity <pause dur="0.5"/> # <pause dur="0.4"/> changes as well # sorry their normal osmolarity changes <pause dur="0.7"/> you give somebody A-D-H by injection <pause dur="0.7"/> they're going to stop their urine osmolarity increasing because you start to <pause dur="0.3"/> retain <pause dur="0.3"/> # <pause dur="1.8"/> water <pause dur="0.4"/> okay <pause dur="0.4"/> so this is a person who's not drinking remember water deprivation test <pause dur="0.4"/> so if you're not drinking your plasma osmolarity will go up <pause dur="0.7"/> okay <pause dur="1.0"/> you give them <pause dur="0.2"/> A-D-H <pause dur="0.8"/> and they're going to stop their plasma osmolarity increasing because although they want to <pause dur="0.4"/> carry on because they're still not drinking <pause dur="0.4"/> the A-D-H will cause them to <pause dur="0.4"/> retain water <pause dur="1.3"/> okay is that clear on my <shift feature="voice" new="laugh"/>second time round <shift feature="voice" new="normal"/> <pause dur="0.7"/> okay so <kinesic desc="indicates point on slide" iterated="n"/> this is somebody with # <pause dur="1.0"/> # one of the forms or both forms of diabetes insipidus you don't know which to this point <pause dur="0.3"/> so you deprive them of water <pause dur="0.6"/> they still pee a lot of

urine <pause dur="0.4"/> so their plasma osmolarity will not increase it doesn't go up at all if you notice <pause dur="0.5"/> they just still # maintain their # dilute plasma <pause dur="1.2"/> you give them A-D-H okay <pause dur="0.7"/> so if it's somebody who has a defect in the brain who can't make or secrete A-D-H <pause dur="0.3"/> you give it to them <pause dur="0.3"/> they respond as normal <pause dur="0.3"/> remember they've got very # <pause dur="0.4"/> dilute urine here <pause dur="0.5"/> # you give them this <pause dur="0.3"/> and they concentrate their plasma rather concentrate their plasma <pause dur="0.6"/> to # <pause dur="0.3"/> as you would expect from A-D-H <pause dur="1.7"/> if you give # somebody with nephrogenic A-D-H <pause dur="0.3"/> they have absolutely no way of responding to it so you don't see any change in the response whatsoever <pause dur="1.2"/> okay <pause dur="0.3"/> so this is the way you can tell them apart <pause dur="0.3"/> deprive somebody of water <pause dur="0.5"/> then give them # an A-D-H injection <pause dur="0.5"/> if you see a change in the <pause dur="0.2"/> # urine osmolarity <pause dur="0.6"/> then they've responded to A-D-H <pause dur="0.4"/> and they've got central <pause dur="0.2"/> diabetes insipidus <pause dur="0.6"/> you give them # an injection of A-D-H and they've got a problem with their kidney <pause dur="0.4"/> you see absolutely no change <pause dur="0.3"/> yep sorry </u><u who="sm0441" trans="latching">

with the <pause dur="0.2"/> nephrogenic form do they hypersecrete A-D-H <pause dur="0.2"/> do they have like a lot of A-D-H in their blood that </u><u who="nf0440" trans="overlap"> yep </u><u who="sm0441" trans="overlap"> they start to respond to </u><pause dur="0.7"/> <u who="nf0440" trans="pause"> probably yes <pause dur="0.3"/> # if you were to actually measure their A-D-H they will be producing lots because they're trying to <pause dur="0.2"/> # <pause dur="0.3"/> concentrate their urine so they're <pause dur="0.3"/> they're overproducing <pause dur="0.2"/> to try and compensate but of course it has no effect <pause dur="0.4"/> wherever the defect is <pause dur="2.4"/> but you normally having said they <pause dur="0.5"/> it's not <pause dur="0.3"/> you wouldn't normally just measure their A-D-H as a diagnostic # <pause dur="0.3"/> tool it's a clue but you would normally do a water deprivation test <pause dur="3.2"/><kinesic desc="changes slide" iterated="n"/> okay <pause dur="0.8"/> so just to reiterate <pause dur="0.3"/> the important factors <pause dur="2.9"/> the length of the loop of Henle is important <pause dur="0.5"/> the longer the length of the loop of Henle <pause dur="0.4"/> the more concentrating ability you've got <pause dur="0.7"/> and there's remember i said to you it's the <trunc>juxta</trunc> # medullary # nephrons that are important there's only fifteen per cent of your nephrons are of this strain this type <pause dur="0.6"/> but those

are the ones that are actually important for forming the osmotic gradient within the medulla <pause dur="2.6"/> you've got the rate of sodium reabsorption so those sodium pumps that are working in the thick ascending loop of Henle <pause dur="0.6"/> the more efficiently they work <pause dur="0.3"/> the more the higher the osmotic <pause dur="0.2"/> # concentration in the medulla's going to be so if you inhibit those from working for some reason <pause dur="0.5"/> you don't develop such an osmotic <pause dur="0.2"/> gradient <pause dur="0.3"/> and don't reabsorb so much water <pause dur="0.5"/> so <pause dur="0.3"/> # some diuretics <pause dur="0.3"/> interfere with these pumps <pause dur="1.9"/> # obviously if you've got changes in the # G-F-R so your rate of sodium chloride delivery to that part of the nephron <pause dur="0.5"/> alters that will also alter your # <pause dur="0.7"/> ability to # <pause dur="0.7"/> <trunc>reabsor</trunc> to create the osmotic gradient and therefore reabsorb water <pause dur="2.7"/> the flow rate <pause dur="0.7"/> if you've got very high filtrate flow rate <pause dur="0.3"/> through the loop of Henle <pause dur="0.4"/> it's going to wash everything through the loop <pause dur="0.5"/> more quickly <pause dur="0.3"/> than all the # functions can actually # the counter current mechanism can work properly <pause dur="0.6"/> so if it flows too quickly

through like you've got a really high G-F-R <pause dur="0.5"/> # you don't develop a very good # counter current system <pause dur="0.6"/> the osmotic gradient is not as strong as it could be <pause dur="0.4"/> therefore you tend not to concentrate your urine so well so you would produce dilute urine in that case <pause dur="2.3"/> and the protein content of diet <pause dur="0.9"/> remember urea comes from protein it's a breakdown product <pause dur="0.5"/> so in theory if you have a high protein diet <pause dur="0.5"/> there's high urea in the blood <pause dur="0.6"/> so that's more urea that can go into the # medulla <pause dur="0.5"/> and in theory that increases the osmotic potential and there is some evidence that people with high protein diets do concentrate their urine <pause dur="0.5"/> more efficiently than people with low protein diets <pause dur="0.9"/> having said that and we're not talking about it yet in the module <pause dur="0.4"/> but if you've got renal failure <pause dur="0.4"/> remember one of the things you look for is an increased in the urea in the # blood <pause dur="0.4"/> and the plasma because you can't filter it and you can't deal with the urea properly <pause dur="0.3"/> so if

you've got kidney disease or kidney failure <pause dur="0.3"/> you might actually want to consider limiting the protein diet and certainly people <pause dur="0.4"/> with # <pause dur="0.4"/> end-stage renal failure have a low protein diet because they can't get rid of the urea <pause dur="0.6"/> so <pause dur="0.2"/> normal people there's some evidence that if you eat lots of protein <pause dur="0.4"/> you'll concentrate your urine more and pee less <pause dur="1.0"/> and then you want the osmotic potential of the tubule cells so you obviously you need antidiuretic hormone or A-V-P <pause dur="0.4"/> to be present to allow the water reabsorption to occur <pause dur="0.3"/> so you've basically got the length of the tubule <pause dur="0.4"/> the flow rate <pause dur="0.3"/> and then the efficiency at how the water moves out of the <trunc>f</trunc> <pause dur="0.3"/> <trunc>ur</trunc> # filtrate or urine into the # <pause dur="0.6"/> kidney <pause dur="0.3"/> and the efficiency of the sodium pumps and the counter current mechanism <pause dur="1.2"/> and that's it <pause dur="0.5"/> oh and the medullary blood flow obviously if you've got very high blood flow going through the vasa recta it will still wash stuff out <pause dur="1.2"/> so i just want to remind you next week's acid-base balance <pause dur="0.5"/> and this kind of fits in

with your respiratory module <pause dur="0.3"/> so i think you do a bit of acid-base tomorrow it's not kind of <pause dur="0.8"/> i've looked at it in the module booklet and it's not kind of listed as acid-base <pause dur="0.4"/> but you do do some <pause dur="0.3"/> <trunc>carb</trunc> # some <pause dur="0.3"/> tomorrow <pause dur="0.5"/> and there is some following on from the urinary module next week so <pause dur="0.4"/> this week's respiratory <pause dur="0.2"/> and next week's respiratory kind of fit in slightly <pause dur="0.4"/> with the # kidney acid-base because the two of them work together the lungs and the kidney to regulate it so <pause dur="0.8"/> # <pause dur="0.2"/> group work starts about quarter to eleven ten to eleven <pause dur="0.4"/> okay and if you've got any questions at all <pause dur="0.3"/> come and see me