nm0572: right okay settle down everybody [0.7] er [0.7] i think i'm meant to be 
talking to you about glomerular pathology [0.5] er i'm not a pathologist [0.5] 
er [0.6] a pathologist perhaps should be giving [0.4] this talk perhaps they 
shouldn't [0.9] er [0.3] i don't think we could get a pathologist to do it so i 
was asked to do it [1.4] so er [0.6] like all good er [0.3] lecturers i'm not 
going to teach you what i said i'm going to teach you [0.5] and i'm going to 
talk to you a bit [0.3] about glomerular disease [0.2] and bring in a bit of 
pathology [0.3] i-, if i can [0.5] i remember being taught this as a medical 
student [0.4] er [0.3] and er we had a lecture a very dry lecture pathologist 
who went through [0.3] all thirty forty [0.2] slides which we didn't understand 
which had pink blobs on it [0.4] and er i don't 
remember anything of the lecture or even the go home message that i thought 
well i'm not going to do the same [0.5] if you want your pink blobs [0.2] if 
you like your pink blobs [0.3] then it's all in the books there are there are 
[0.2] books of glomerular pathology [0.2] er [0.4] i would however recommend 
this book Textbook of Renal Disease by Whitworth and Lawrence [0.3] this is a 
second edition but i think er there are further editions [0.4] and [0.4] as 
well as having the pink blobs which are not pink [0.4] er [0.2] they actually 
have some much better diagrams [0.3] i'm sure you can't see that from the back 
but [0.2] er this is an electron microscopy [0.3] er of a glomerulus [0.3] this 
is light microscopy that's amino fluorescence [0.4] and i f-, personally find 
that the [0.2] electron micrographs are easier to understand [0.4] er and this 
is book is full of electron 
micrographs [0.3] of various renal diseases [0.3] including diabetes [1.3] okay 
[0.4] so if i'm not going to talk about what i said i'm going to talk about 
what am i going to talk about [0.4] er [0.2] i'm going to talk about [0.3] 
nephrotic syndrome [0.7] er chronic glomerulonephritis and [0.2] glomerular 
disease in general [0.3] you have got a handout i'm sorry [0.3] er [0.4] 
there's been a [0.3] photocopier cock-up [0.3] and i've only got about ten down 
here so you can [0.3] they they are coming you will have them at the end and 
maybe it's a good idea that you [0.4] pay a bit of attention [0.6] okay [0.4] 
so [0.3] who said [0.8] i've got Bright's disease and he's got mine [2.4] 
anybody heard that one [3.9] i've got Bright's disease [0.2] and he's got mine 
[7.2] oh dear [0.3] it's going to be a long long session this morning [2.6] 
anybody [0.2] calculated guess [0.3] American comedian [0.2] nineteen-thirties 
[1.4] 
sm0573: er [0.9] 
nm0572: who would say it [1.4] 
sm0574: Marx [0.3] 
sm0575: Marx [0.3] 
sm0576: Marx 
sm0577: Marx 
nm0572: Marx Groucho Marx okay [laugh] i've got Bright's 
disease and he's got mine [0.3] so there's a bit of a joke in there it's 
obviously not a very funny joke [0.4] [laughter] it's obviously a er a joke 
that's only appreciated by kidney doctors [0.4] [laughter] er [0.4] and er [0.
2] so i'm going to have to explain this joke to you [0.6] er [0.2] any joke 
that needs explaining is not funny actually is it [0.8] [laughter] er [0.5] 
okay [0.2] Bright [0.4] who was who was Bright Richard Bright [laughter] [0.5] 
shush come on anybody [0.9] who was Richard Bright has anybody heard of [0.4] 
Bright's disease [2.4] still lurking in your textbooks actually if you look for 
it [2.2] well Richard Bright was the or s-, [0.3] is said to be the father of 
[0.2] British and world pathology [0.4] published his thesis [0.5] eighteen-
twenty-seven you still read it [0.3] top floor of the Wellcome bulding in the 
Euston Road what [0.3] the library in Guy's if you go and read the actual words 
or actual 
Richard Bright [0.3] he's er [0.2] said to be our [0.2] our forefather [0.3] 
and and [0.4] nephrology started to exist as a specialty [0.3] er [1.1] they 
say when when when Bright wrote his thesis [0.3] i actually think it probably 
only started about twenty or thirty years ago when we started dialysing in the 
U-K [0.4] er [0.4] but er [0.3] the story as they say goes back to to eighteen-
twenty-seven [0.4] so Richard Bright was a nephrologist perhaps the world's 
first nephrologist at Guy's Hospital [0.3] and Guy's [0.2] still considers it 
the world centre it isn't [0.5] but they they still [0.2] er consider 
themselves the you know the centre of that's why everything in in the U-K and 
[0.2] just 'cause we invented it we think we're we're the best at it and have 
[0.3] have er rights over it [0.7] er [1.2] and er [0.4] nobody actually nobody 
knows what Bright's disease is [0.4] er [0.5] and [0.4] some people think it's 
nephrotic syndrome some people think it's glomerulonephritis [0.3] er [0.7] 
it's [0.4] better not not to define it 'cause obviously Bright didn't define it 
[0.3] i take it to be [0.2] er [0.3] synonymous with nephrotic 
syndrome [0.7] er [0.4] which is [0.3] the thing i'm going to talk about at 
the i-, in the first stage of this talk [0.4] er i'm going to later on move on 
to [0.2] glomerulonephritis [0.4] and and which is one of the causes of 
nephrotic syndrome [0.5] okay [0.4] so lady here [0.3] have a have a bash at at 
defining nec-, nephrotic syndrome [2.4] er have you heard of nephrotic syndrome 
sf0578: yep [0.2] 
nm0572: okay [0.7] anybody else lady behind in the blue with the glasses [0.5] 
have a go at defining nephrotic syndrome actually there there is a set 
definition [0.6] for this one [1.3] 
sf0579: er [0.9] i don't know [0.6] 
nm0572: okay anybody else anyone want to have a go at it [1.0] come on [0.5] 
doesn't matter if you're wrong [1.9] ladies at the front [0.2] nephrotic 
syndrome have you heard of it 
sf0580: 
i can read it out of here 
nm0572: go on read it out [laughter] [1.2] 
sf0580: it's defined as proteinuria [0.2] 
nm0572: yes 
sf0580: sufficient to cause hypoalbin-, [0.3] albiniu-, bleurgh [laughter] i 
can't say that 
nm0572: yeah yeah yeah right 
sf0580: intense peripheral oedema [0.4] 
nm0572: very good okay [0.5] so [0.2] er [0.2] there are three features to the 
definition of nephrotic syndrome [1.2] er [0.6] hypo [1.4] al-, [0.3] i can't 
say it neither [0.4] hypoalbuminaemia [0.2] that's low albumin in the blood [0.
8] er [0.3] proteinuria of greater than what [2.0] does it say there 
sf0580: no it doesn't say 
sm0581: three grams over twenty-four hours [0.9] 
nm0572: 
it's it's actually ver-, i-, every book's different it's [0.2] most of the 
world 
sf0580: five grams 
nm0572: takes it to be three-point-five [0.3] the U-K we used to take it to be 
five perhaps this is an American definition [0.8] er [0.8] and peripheral 
oedema [0.9] and these are the three features of of nephrotic syndrome [1.7] 
okay [0.2] we can't get away with that er type definition with abou-, without a 
few buts [0.4] clearly nephrotic syndrome [0.4] is an arbitrary definition you 
don't go from nought to three-point-five [0.3] you go through other numbers [0.
6] er [0.3] and [0.4] there is such a concept as mild proteinuria moderate 
proteinuria [0.4] more severe protein-, [0.2] and what you could say [0.4] is 
that nephrotic syndrome is [0.3] if you like severe proteinuria [1.4] er [0.4] 
having said that [0.7] how mu-, [0.4] in terms of the amount of protein that 
you eat [0.6] er how much [0.3] do you think three-point-five is [0.3] what 
proportion of the protein that you eat [3.7] how much protein do we eat a day 
[2.0] any nutritionists in the room ex-dieticians [1.7] anorexics [2.0] 
[laughter] 
medical students don't ge-, get anorexia [1.6] don't mention that [1.7] how 
much protein do we eat a day [2.0] eighty grams roughly i mean it depends on 
whether you eat ten steaks a day or [0.4] two chickpeas or whatever [0.3] 
[laughter] but you know that's a a a an average in in a Western diet [0.7] and 
[0.2] if [0.2] you are losing [0.2] three-point-five grams a day [1.5] and that 
leads to the spiel we tell the patients [laughter] which is what [0.5] what 
spiel do we give the patient lady lady here [0.3] if i was [0.2] if if if you 
if you're trying to explain [0.9] nephrotic syndrome to a patient [1.8] er [1.
7] what would you tell them [1.1] how would you [1.0] put that little triad 
together [2.4] come on have a go what [0.9] so you've got no protein in the 
blood [0.5] lots of protein in the urine [0.3] peripheral oedema [1.9] you're 
the doc i want to know why have i 
got this [3.2] lady next to her [1.4] 
sf0582: it's not in layman's terms [laughter] 
nm0572: well have a go in non-layman's terms how how how would you explain in 
non-layman's terms 
sf0582: er [0.2] if you're losing [0.4] protein [0.5] [0.5] 
nm0572: yeah and that is therefore leads to [0.5] 
sf0582: er [1.5] it's hard to keep [0.8] fluid [1.0] in [0.5] 
nm0572: yeah very good [1.0] i mean i think what i would say to a patient is [0.
3] you're losing protein in your urine here i can see it on my dipstick [0.6] 
and therefore you don't normally lose protein in your urine and therefore 
that's why you've got low levels in the blood [0.2] here [1.1] and for various 
complicated reasons that i can't explain to you today because it's all too 
complicated [0.3] [laughter] er and it's probably [0.7] er [laughter] all the 
water back into the cells isn't it [0.5] 
you can try explaining that to [0.2] to Joe Public [0.4] but what i would say 
to a patient [0.7] with er [1.1] hypoalbuminaemia and the line is usually taken 
at less than thirty grams per litres [0.2] normal is thirty-five to fifty [0.8] 
er [0.7] losing protein in the urine [0.2] leads to low protein levels in the 
bu-, blood which in [0.4] in a [0.2] long and convoluted er [0.7] er a way 
that's too complicated to explain to you here today oh i've got a patient to 
see in another five minutes [0.4] er [0.6] leads to peripheral oedema [1.8] but 
[1.0] there [1.0] there's a big but there [0.2] you're eating eighty grams a 
day [1.7] and you're getting low levels of protein in the blood [0.7] with 
small amounts of proteinuria and therefore what's wrong with the theory [2.5] 
what's wrong with the spiel [0.2] our colleagues come out with [2.6] 
sm0583: where's the rest of it gone [0.5] 
nm0572: very good [0.2] okay [0.4] so er [0.2] it's not enough is it [0.5] er 
[0.2] you know you're only losing small amounts of 
protein in the urine [0.6] and you're eating lots [0.3] of protein [0.6] so 
where's the rest of it gone [0.4] exactly [0.5] and er the the the answer is 
that nephrotic syndrome is probably not [0.2] a renal disease [0.3] [0.4] er [0.
4] and i'm going to expand on that in a minute [0.4] er but that's [0.2] you 
know if you [0.3] forget everything else i say about nephrotic syndrome it 
probably isn't just a renal disease [0.3] it's probably a problem of [0.2] 
protein metabolism in a variety of organs [0.4] including the liver and why 
must the liver be involved [0.8] 
sm0583: it makes albumin [0.5] 
nm0572: it makes albumin okay so [0.5] if you've got low albumin levels in the 
blood and you're not excreting it [0.5] there's probably a problem with 
synthesis [0.4] and and most proteins including albumin are made in the liver 
[1.4] so there's probably liver trouble in nephrotic syndrome [0.3] but we'll 
call it nephrotic syndrome for the moment [0.9] er [0.8] okay [0.3] so [0.5] 
can anybody tell me [0.2] some er causes of nephrotic 
syndrome [4.9] causes [1.1] most important cause [0.5] clue in the previous 
lecture [0.6] 
ss: diabetes [0.5] 
nm0572: diabetes okay [1.1] so diabetes by far and away the commonest cause of 
nephrotic syndrome if you think about it what nephrotic syndrome is it's stage 
four of the Mogensen classification [0.2] we talked about in the first lecture 
[0.9] er [0.4] so [0.8] but diabetes is not the only thing that can affect the 
glomerulus [0.7] and the glomerular basement membrane [0.5] and [0.2] loads of 
other systemic diseases such as what [0.3] er could affect the glomerulus [1.0] 
sm0584: S-L-E [0.2] 
nm0572: S-L-E very good lupus any others [0.4] re-, read your list [0.5] 
sm0584: okay the tumour amyloid [0.6] H-S-P [0.2] 
nm0572: yeah [0.5] Henoch-Schoenlein purpura [0.5] 
sm0584: er drugs including [1.3] penicillamine [0.2] 
nm0572: gold 
sm0584: gold [0.6] 
nm0572: 
sm0584: and congenital nephrotic syndrome 
nm0572: 
yeah [0.2] i mean the the [0.4] generally speaking if you have to learn 
something in the form of a list [0.2] don't bother [0.6] you won't forget it 
you won't remember it [0.5] [laughter] er [0.4] and er [1.0] rather than learn 
lists [0.3] it's sometimes better to use [0.3] er what we call the have you 
heard of the surgical sieve [0.5] anybody [1.2] introduce any surgeons giving a 
lecture and talk about the surgical sieve [1.8] no [0.2] okay [0.4] you've had 
lectures from surgeons [0.3] presume it bu [0.5] surgeons are very simple 
people [0.4] er [0.2] don't repeat that [0.5] and er they have to have ways of 
remembering things [1.1] right where did i leave my Bentley [0.3] [laughter] 
and [0.9] er [0.3] no no enough of that [1.4] er i'll give you my surgical 
sieve you're welcome to use it or [0.2] better to invent your own one [0.7] and 
really a surgical sieve is a way of remembering the causes of anything and it 
it can be applied to [0.4] er epilepsy [0.9] pyrexia of unknown 
origin [0.3] this whatever [0.4] er [0.5] degenerative [0.6] effective 
inflammatory metabolic [0.2] including all the failures endocrine diabetes and 
other and other [0.2] neoplastic [0.5] benign malignant primary secondary 
iatrogenic drugs [0.4] er [0.3] either er er prescribed drugs or [0.2] er 
recreational drugs trauma [0.7] haematological [0.4] and that's just one 
surgical sieve my it's my surgical sieve DIANITH invent your own [0.4] er use 
mine if you want to [0.3] and [0.4] er so if somebody says to you what are the 
causes of nephrotic syndrome you don't want to have to look it up in a book you 
[0.2] just try to work it out from first principles degenerative including [0.
2] amyloid you know [0.2] infective including [0.2] T-B malaria and metabolic 
including all the failures endrocrine diabetes neoplastic [0.4] cancers such as 
[0.3] er lymphoma and other things [0.4] er iatrogenic drugs yes [0.4] er 
trauma not really haematological back to lymphoma [0.4] 
er [1.1] don't learn don't learn a list don't buy the stupid American books of 
lists absolute rubbish [0.4] er you won't remember them [0.3] and they'll just 
irritate you and you'll have a panic and don't know the [0.2] twenty-eighth [0.
2] cause of clubbing [0.4] [laughter] don't buy books of lists [0.5] er [1.9] 
okay [0.3] so [0.4] er [0.9] pathophysiology of nephrotic syndrome much mo re 
interesting than the list [0.5] er [0.3] what [0.2] causes it well we've 
rubbished the [0.5] the patient explanation [0.6] protein in the urine [0.3] 
low plote-, protein levels in the blood [0.4] er peripheral oedema [0.5] can we 
get at it in in a bit more detail the more articulate patient [1.1] well we can 
a bit er [0.3] without [0.2] clearly [0.2] there's got to be something wrong [0.
3] with the glomerulus [0.5] if you develop nephrotic syndrome [1.0] er [0.4] 
and [0.9] the glomerulus [1.8] a million glomeruli per kidney [0.3] er [1.2] 
don't think of it like that don't think of it the [0.2] 
don't think of a kidney like that with a million glomeruli in [0.5] it's a bad 
[0.2] visual concept [0.5] er [1.6] it's much better to think of a kidney [0.7] 
like this [0.6] which is a tube [1.1] er [0.5] and [2.3] with something in the 
middle [1.8] er which we call the glomerular basement membrane [0.8] and that's 
really what a kidney is [0.7] so what comes in at this end [1.2] 
ss: blood [0.5] 
nm0572: blood [0.4] and what comes out that end [0.6] 
ss: urine [0.2] 
nm0572: urine [0.9] and what do we call [0.3] wee-wee when it's in here [0.2] 
ss: filtrate 
nm0572: glomerular filtrate [0.4] that's what a kidney is [1.2] it's a thing 
that converts stuff into other stuff [0.2] but that stuff is really the same as 
that stuff [0.3] but i've got a few things [0.4] er added and taken 
away at various points [0.5] proximal convoluted tubule et cetera [0.3] it's 
still stuff [1.2] and some of it goes back again [0.8] and er [0.6] a medical 
student er said to me the other day that my er tube analogy was completely 
wrong [0.5] and er that was it was much more complicated how could i possibly 
[0.3] er [0.2] call the kidney just a tube this wonderful organ that i love so 
much [0.5] [laughter] er and i-, and er [0.6] he was right to an extent but the 
only thing i've really missed out it's really [0.4] there's another bit there 
really isn't there [0.7] you know [0.3] er you have [0.2] an afferent an 
efferent arteriole and a tube and some of it does go back i mean he was right 
[0.7] he was [0.3] er [0.2] er d-, wouldn't let me get away with my [0.3] er my 
tube analogy [0.3] but er [0.3] i i still think my [0.2] it's easier to think 
of it as a tube [1.1] okay [0.3] and so normally what happens is that you have 
big things in the blood like cells [0.8] and 
other things like proteins some of which are big [0.5] and some of which are 
small like albumin [1.2] but they're bigger than a certain critical pore size 
[1.0] and they come piling down here [0.3] and meet the sieve [0.8] and [0.2] 
generally speaking they don't get through and what does get through [2.5] so 
proteins and cells don't get through but what does get through 
sm0585: ions [0.3] 
ss: ions 
nm0572: ions such as [0.4] 
ss: sodium 
nm0572: sodium potassium phosphate and all the rest of it [0.6] most of which 
are then reabsorbed [0.4] some of which are then secreted at various points [0.
4] sodium is almost completely reabsorbed ninety-eight per cent of it [0.7] er 
[1.0] at various stages in the [0.3] er [0.3] proximal and distal convoluted 
tubule [0.7] er and the cells just go back again down the medical student's bit 
[0.5] er and and just go round again [1.0] 
but in glomerular disease [0.3] there's trouble with the sieve [1.5] er [0.2] 
if we just [1.2] look at the sieve in a bit more detail and look at the cross 
section of my tube [1.6] it's not really just er a a single tube [0.4] it's a 
tube with [0.4] like all tubes in the body it doesn't matter whether they're a 
blood vessel [0.5] er [0.6] a er [0.4] a bit of the nephron [0.3] most tubes in 
the body have three layers [0.4] they have an endothelium [0.4] a basement 
membrane and an epithelium and the kidney's no different [0.7] and [0.4] the 
tube [0.3] is the same [0.8] er so we've now we've sorry [0.2] just to [0.5] 
realign you [0.3] when we're talking about [0.2] the sieve [0.6] and and what 
what the sieve looks like [1.5] and now as we look at this in cross section [1.
9] er [1.3] what you have is something like that [0.8] with stuff going through 
here [0.9] urine glomerular filtrate blood so 
blood [0.3] glomerular filtrate and urine [0.4] and it's got to get through the 
wall [1.1] and so it has to go through [1.0] the [0.3] endothelium the basement 
membrane and the epithelium [1.1] and this will be true whether it's a blood 
vessel or whether it's a tubule in a kidney or most tubes in the body [0.4] 
it's got to get through there [0.8] and normally what happens is it doesn't get 
through it and it all comes back again all the cells and the proteins [0.6] but 
in glomerular disease and diabetes it's it's it's the classic cause of 
glomerular disease [0.4] you get trouble at t'mill [0.8] and something happens 
[0.3] probably [0.2] to the basement membrane [1.1] but in other glomerular 
diseases other bits of it go wrong [0.7] such as in minimal change nephropathy 
the podocytes get defaced or knocked off [0.6] either way something happens [0.
3] to the wall [0.3] of the glomerulus [1.4] and i think it's better not to 
think of 
the glomerulus as a glomerulus just think of it as part of the tube [0.6] er [0.
3] because [0.3] you know [0.9] you can say oh well you know there's the thingy 
there's the thingy [0.2] Bowman's capsule thingy thingy thingy these are all 
quite different [0.6] they're not really it's the same tube [0.6] and you just 
need to go [0.2] and lengthen it out [0.7] and er you can start to understand 
how the kidney works [0.5] the glomerulus is just part of the tube it's just [0.
2] the glomerulus is a scrunched up capillary that's what a glomerulus is [3.2] 
don't worry that this hasn't occurred to you before and i know you're thinking 
that's probably a load of namex rubbish [0.3] er [0.2] it i-, [0.8] it is a 
pretty good analogy [0.3] or a pretty good [0.2] visual concept of of what a 
kidney is [0.4] er [0.3] even if it is simplistic [1.4] and when you start 
looking at glomerular pathology [0.2] i think one of the problems in the way 
it's taught [0.3] 
is that they they they don't start from these very simple concepts they just 
start from [0.4] pictures of pink things with blobs in [0.6] and and and you 
you can't imagine [0.3] what it is or where it is or or how it's doing the 
damage [0.6] so going back to nephrotic syndrome [0.4] if you've got [0.3] a 
problem with leaky glomeruli [1.5] you're going to either have a problem with 
the [1.1] endothelium [0.3] the basement membrane or the epithelium [0.9] so 
what can go wrong [0.3] in [0.3] the [0.3] glomerular basement membrane [1.0] 
that would let [0.2] bad things through [4.7] gentleman in the blue there [1.2] 
sm0586: er 
nm0572: what could go wrong [0.8] 
sm0586: some of the [0.3] transport proteins might be broken or some of the 
pores might be larger than 
nm0572: very good so [0.3] that's the so-called pore theory [1.3] er so you get 
holes appearing [0.7] er what else c-, conceptually could go wrong [2.1] 
sm0587: 
defects in collagen synthesis [0.4] 
nm0572: yeah [0.4] leading to what [0.6] 
sm0587: er [0.2] 'cause it's collagen [0.3] 
nm0572: yeah 
sm0587: and goes in [0.4] er [0.4] pores [1.2] 
nm0572: well we have pores we have holes in the pores [1.4] do you you you're 
getting there [0.5] you [0.3] defects in collagen synthesis could lead to [0.2] 
problems with permeability [0.4] so [0.2] if you like the function [0.9] of the 
sieve [0.6] er [0.4] and that the so-called permeability theory [0.6] er [0.4] 
there is er a final theory [0.5] er [0.5] which er relates to charge [0.4] er 
[0.2] and i don't really understand but [0.3] er [0.3] there is [0.2] a charge 
gradient apparently a-, a-, across the glomerulus [0.6] and er sorry i have to 
look this up 'cause i always forget [0.6] er [3.4] yeah most proteins are very 
negatively charged [0.9] and they therefore [0.4] repel each other and [0.4] 
also the glomerular basement membrane is [0.4] is appa-, apparent-, i don't 
know how the hell they do this [0.5] but er [0.3] negatively charged [0.2] and 
there is a natural 
repulsion to going through it [0.4] and apparently changes in charge could 
possibly explain why [0.3] why [0.3] er pores develop so there is a link in the 
charge theory to the pore theory [0.5] er [0.2] but the bottom line is that we 
don't know [1.0] and er diabetes [0.2] is a is a classic example of a disease a 
glomerular disease [0.3] where we we don't know which of these theories is 
correct but somehow [0.4] the the high blood sugar or more likely the blood 
pressure [0.4] er affects the glomerular basement membrane and starts to let 
things through [0.9] there is a trendy theory at the moment that the [0.3] 
proteins that are allowed through [0.6] are not just a marker [0.3] of 
glomerular disease [0.2] and proteinuria is the hallmark whenever you see 
significant proteinuria [0.3] greater than say two grams per twenty-four hours 
[0.2] up to one-fifty milligrams is normal per twenty-four hours [0.7] so you 
eat about eighty a day [0.2] and you [0.2] er excrete about one-fifty so 
normally [0.2] 
some protein but not much does go through the glomerulus about a hundred-and-
fifty milligrams a day [0.7] er [1.1] and [0.3] er [1.1] in diabetes and other 
glomerular diseases [0.5] it's considered that the proteinuria which is by this 
stage in the [0.2] er the later stages of the nephron the proximal convoluted 
distal convoluted tubule et cetera [0.3] er is itself toxic [0.3] and somehow 
[0.2] again then makes the problem worse [0.8] er and and one of the groups in 
namex namex [0.2] er is got er several research groups [0.3] we don't do too 
much research in namex but namex has a big [0.3] er research area in in 
nephrology [0.3] and and they're looking into this theory of whether the 
proteinuria in itself is is is toxic [0.3] and makes the problem worse [0.3] 
what's interesting is now electron micrographs have been done [0.3] and these 
holes are are [0.2] which have to be there there has to be a pore [0.2] 'cause 
sometimes 
you may physiologically want to open them up and send things through or not 
send things [0.4] send s-, things through [0.4] but [0.2] er [0.2] it may be [0.
9] er [0.3] that er [0.8] er the proteinuria is [0.3] part of the problem of 
course the the treatment is is is not identified but that [0.3] that is one of 
the current theories [0.8] okay [0.5] so [0.2] they're some of the theories 
about why we get proteinuria the hallmark of glomerular disease [1.5] er [0.2] 
how can how do we prove proteinuria [1.7] how do we [0.3] how do we [0.2] find 
out whether somebody has proteinuria [0.7] 
ss: dipstick 
nm0572: dipstick okay [0.4] how do you do a dipst-, has any-, who's done a 
dipstick [0.2] anybody [0.7] a few people [0.8] has any-, [0.2] put your hand 
up if you've not done a dipstick [1.6] good all right so you've all done a 
dipstick [0.4] okay [0.3] so very simple you get some wee-wee you put the dip-, 
dipstick in take it out look at it [0.8] and and what does it tell you about [0.
7] about [0.2] protein [0.5] what what what's 
the scoring system [1.5] 
sf0588: [laugh] [1.1] er just whether it's there or whether it's not [0.3] of a 
certain amount 
nm0572: no that's a [0.4] yeah there is a scoring system usually [0.7] 
sf0589: is it just pluses [0.2] 
nm0572: pluses [0.2] yes pluses [0.5] er [0.2] one of the problems is that all 
the dipstick kits are different they all use different assays and have 
different levels [0.3] of proteinuria that leads to p-, [0.2] to pluses and 
this is one of so you can't compare one hospital to another one ward to another 
[0.6] but most of them work on some system [0.3] of colouring [0.4] trouble if 
you if chu-, if you're colour-blind you can't do it [0.3] where you either get 
[0.2] no colour [0.5] or a trace [0.3] one plus [0.2] two pluses or three 
pluses [0.6] but rather irritatingly some dipsticks also four pluses [0.6] er 
[1.0] and [0.3] that's [0.3] one of the simplest ways of measuring proteinuria 
[0.3] er [0.2] it's a very simple test [0.4] it's er a test beloved of G-Ps a 
test beloved of nephrologists [0.3] 
i'll talk a bit in a minute about [0.3] er why we like it so much and and the 
problems with it [0.4] what what do you think is the the the the good [0.3] 
side of a a urinary dipstick [0.5] gentleman in the green top there [0.6] wh-, 
why why do we like urinary dipsticks [0.5] 
sm0590: it's quick and easy [0.3] 
nm0572: quick and easy cheap [0.2] painless no risk [0.4] reliable [0.6] okay 
lady next to her [0.3] you had a headband on last time you thought you'd hide 
by not wearing a headband [0.3] [laughter] er [0.2] wh-, why er why what's 
wrong what's [0.2] wrong with urinary dipsticks [1.2] 
sf0591: it's not always accurate [0.4] 
nm0572: they're not al-, yeah let's expand on that you're right [1.1] what way 
are they not accurate [3.2] there's some handouts coming round now by the way 
sorry the answer to this question is [1.8] anybody 
else why why are they not accurate [0.3] 
sm0592: it's up to the person who reads it [0.6] 
nm0572: yeah i mean there there is [0.2] problems with the colour vision you 
know how do i know [0.3] that you see the same bl-, [0.2] blue as everybody [0.
4] [laughter] you know [0.2] er [0.5] er er how do we know what we see is the 
same [0.9] and also it's pretty crude often you're not sure whether it's two 
pluses or one plus [0.2] it may make a lot of difference okay [0.3] and what 
have you're right what other al-, [0.4] that's a very important [0.7] answer [0.
2] what other ways is a urinary dipstick [0.3] 
sm0593: it's only a snapshot [0.3] 
nm0572: it's only a snapshot so we're getting well problem of linear bias again 
[0.3] you know and it you know it may come and go [0.3] particularly if it's 
low level [0.7] any-, anything else [1.1] other problems [0.4] 
sm0594: 
sf0595: it's not a natural number it's just a [0.4] 
nm0572: yeah it's a it's not a natural number [0.2] it's just er some vague 
number of pluses [0.9] what what 
are some more technical problems with a urinary dipstick then [1.4] 
sm0596: does it only measure in like macro [0.7] er 
nm0572: yeah you're getting there [0.3] yeah [0.6] 
sm0596: 
nm0572: it mainly measures what [0.3] 
sm0596: its albumin [0.2] 
nm0572: albumin [0.6] that's the trouble [0.4] it mainly measures albumin [0.3] 
and albumin is one of many proteins and it may not be the protein [0.4] that is 
going through [0.4] the glomerulus which should not be going through [0.2] may 
be globulins may be other proteins [0.5] it may be Bence-Jones protein what 
condition causes Bence-Jones proteinuria [0.5] 
sm0597: myeloma [0.3] 
nm0572: myeloma [0.6] okay so a urinary dipstick would miss myeloma [0.3] very 
important cause of significant proteinuria [1.2] so if you forget everything i 
say in this talk just remember that fact [0.5] that a urinary dipstick measures 
albumin and albumin alone [0.3] there are technical problems with it [0.4] 
and it's not completely reliable it will miss certain diseases [0.9] er [0.5] 
another problem with it which is identified on your [0.2] er handout [0.3] er 
[0.2] is that [0.4] there's no standard setting you know i've told you there's 
nought [0.3] there's a trace [0.2] there's a plus there's two pluses [0.3] 
nobody has ever set a standard you know [0.2] either that [0.2] is equivalent 
to X [0.2] numbers or milligrams per twenty-four hours [0.3] remember [0.2] the 
normal range is up to one-fifty milligrams per twenty-four hours or [0.4] if 
you pass one-and-a-half litres a day that's about [0.3] a hundred milligrams or 
[0.2] or nought-point-one grams per litre [1.0] that's another way of 
expressing it [0.2] actually in namex we get [0.3] a concentration most [0.3] 
er [0.2] countries in the world [0.3] and le-, and cities in in the U-K [0.2] 
we actually get a twenty-four excretion but we have a concentration [0.5] er [0.
3] and that's another problem with this [0.2] with a dipstick it measures 
concentration [0.6] so if you if you're a little old lady who drinks [0.5] 
three cups of 
tea a day you only drink four-hundred mls a day your urine will be concentrated 
[0.3] so that will immediately shift all your values down a bit [1.2] so 
depending on how much you drink it affects the sensitivity of the test [1.7] 
that's why you can't say 'cause it measures the concentration [0.3] that that 
is equivalent to X [0.4] amount of proteinuria for twenty-four hours and that's 
equivalent to Y [1.0] but roughly speaking [0.4] er [0.5] what we would 
normally say is a trace [0.3] you don't necessarily have to investigate but [0.
2] one plus [0.3] or more of proteinuria you should investigate [0.5] and [0.5] 
some people say [1.3] that you start to get one plus when you have greater than 
three-hundred milligrams per twenty-four hours [1.3] in other words [0.2] there 
are levels of proteinuria which are biologically significant in the difference 
between these two numbers [0.3] which are missed by a urinary dipstick [0.7] so 
in other words [0.2] you get false positives [0.4] and you get false negatives 
[0.7] er with 
urinary dipsticks [0.8] false positives [0.3] because there are non-renal 
diseases such as pyrexia [0.2] such as pregnancy such as heart failure [0.2] 
various hydy-, hyperdynamic [0.3] states [0.3] which will give you a trace of 
proteinuria so that's a false positive [0.5] er [0.4] a false negative [0.3] is 
when you miss [0.2] important [0.4] biological levels of proteinuria which a 
dipstick said was a trace [0.3] and was normal [0.5] and if the patient 
happened to drink a bit less it would the-, then have become positive [1.0] but 
nonetheless [0.5] it's not a bad screening test [0.3] er [0.7] and [0.6] i hope 
you don't take those words away from you [0.2] those of you who are going to be 
G-Ps [0.4] and er [0.3] think for the rest of your lives [0.3] as many G-Ps do 
when your patient is apparently well has normal blood pressure a normal 
creatinine and a normal dipstick they don't have [0.3] renal disease [0.2] they 
could easily have polycystic kidney disease [0.4] there are lots of renal 
diseases that don't give you [0.3] normal blood pressure normal [0.3] er 
dipstick [0.3] normal creatinine [0.3] and that 
they are significant [0.6] and so certanly it was [0.3] taught to me as a 
medical student that a [0.2] a urinary dipstick combined with normal blood 
pressure normal renal function [0.3] excludes significant renal disease that is 
not true [0.3] it excludes most [0.5] significant renal disease it doesn't 
exclude cancer in a kidney [0.6] it doesn't exclude polycystic kidney disease 
[0.3] it doesn't exclude many tubular interstitial diseases [0.9] okay [0.3] so 
[0.2] we've knocked or i've knocked [0.2] er the urinary dipstick test [0.3] er 
what do we do instead [0.3] ah [0.4] we've got a much better test twenty-four 
hour urine that's a nice test [0.4] because it gives you [0.2] a nice number [0.
3] and it's reliable [0.7] er [0.2] how do we how do we [0.6] 
sf0598: can i just say the handout [0.3] er er the second page is the same as 
the last handout 
nm0572: is it 
sf0598: this page [0.3] 
nm0572: oh that's a cock-up [0.3] can i have a look [0.7] 
sf0599: 
nm0572: 
yes [0.9] right thank you for spotting that [0.9] okay [0.3] sorry about that 
team [0.8] er [1.1] great [3.6] [laughter] er what i suggest you do is don't 
read the back of that [0.7] okay [0.6] er 'cause it's it's all about diabetes 
[2.3] is that right yeah [0.3] it's all about diabetes [0.7] and [0.7] 
nf0600: i can the [0.3] the photocopier is broken which is why we're late but 
i'll put one in the pigeonholes as soon as i can photocopy them [1.0] 
nm0572: right [0.2] okay [0.2] 
nf0600: that's the best i can do 
nm0572: sorry about that [0.4] er [0.4] cock-up [0.4] [laughter] Dr namex [0.5] 
Dr namex to blame [1.1] and er we will er [0.4] try to [0.5] er address that 
for you [0.3] okay [0.3] well it may be quite good 'cause you might you might 
listen a bit more to what i'm saying [0.5] so er [0.6] what's the problem [0.7] 
how do we do a twenty-four hour protein [0.6] le-, [1.1] you're on the case [0.
7] 
sf0598: you collect [0.2] every [0.3] er [0.7] urine that the patient does in a 
bottle and collect it 
nm0572: mm 
sf0598: put it in the fridge for twenty-four hours and send it to the lab [0.8] 
nm0572: 
how many times have you been to the loo today [1.1] 
sf0601: [laugh] once [0.2] 
nm0572: sure [1.4] 
sf0602: sure [laughter] [1.2] 
nm0572: sure [3.5] how many once [0.6] [laughter] sure [2.0] [laughter] i've 
been at least two i can't possibly at least two [laughter] but i can't remember 
can't remember having been to the loo this morning [0.6] er [0.2] and [0.3] 
it's er [0.4] people can't remember [0.6] and people [0.2] don't remember [0.3] 
to do it [0.7] er when do you start [1.1] [laughter] you know if you're going 
to say to a patient here's a bottle go away and fill up a twenty-four hour 
urine go on start [0.3] fill it up [0.9] now they won't they don't know what to 
do [0.3] and if you do a twenty-four hour urine you have to explain it very 
clearly [0.4] you have to explain to them that [0.7] you want them to start at 
a certain time and usually it's best to say when you get up [0.7] and put every 
[1.1] urine [0.3] that you pass through the day into that bottle [1.0] and then 
stop [0.4] when you get up the following morning but then what if you get up 
in the night [0.6] you know which day is that in [0.8] so it actually becomes 
quite hard to ask them to do a a very simple thing like a twenty-four hour 
urine [0.5] and [0.2] what i normally say is [1.1] write down [0.4] the time 
which you got up [1.9] and then [0.3] put in every urine [0.2] for the 
following twenty-four hours and and you really have to explain in incredible 
detail [0.4] er [0.2] and the problem is one urine sample [0.3] l-, [0.4] in 
there that should be in there or should or or is missed [0.4] messes up the 
whole thing [0.4] if you've taken out perhaps a quarter [0.2] of the day's 
urine output [0.6] so it's intrinsically unreliable i know you're told it's all 
br-, it's brilliant to do a twenty-four hour urine [0.4] but er [0.3] the other 
problem i-, in women [0.5] er is that [0.2] women for the for the boys being in 
the room who don't know this [0.3] er sometimes do wee-wees and poo-poos [0.4] 
at the same time or [laughter] vaguely the same time [0.5] so you can't always 
not exactly the same time [laughter] you know er [0.5] 
er [1.4] [laughter] and er this [laughter] [0.8] you know [1.1] isn't it ladies 
[0.4] [laughter] you know to control these things [0.4] and you know how how do 
you [0.3] [laughter] you know [1.4] you know [1.5] how do you do it [0.6] y-, y-
, y-, you know in a pot do it in there w-, what [0.6] [laughter] how do i sit 
on that thing you know [0.3] and it's very difficult [laughter] and they're 
they're given these er [0.5] er pots to wee into and then you tip that and oh 
ah [0.3] all down his shoes [1.0] [laughter] [0.5] i've got it on my fingers 
[laughter] horrible [0.4] you know that's quite difficult to do a twenty-four 
hour urine and er so er the bottom line is i rarely organize them [0.3] or if i 
do organize them [0.3] er i explain very clearly to the patient exactly what i 
want them to do [0.3] 'cause it affects clinical decision making [0.2] and a s-,
and a 
small difference between say [0.2] two grams per twenty-four hour proteinuria 
[0.2] one gram or three grams could decide whether we do a renal biopsy or not 
[0.8] so it's got to be accurate [0.7] and ladies if you order with ladies it's 
[0.4] you've got to give them the equipment [0.2] you know [0.2] you give them 
one of the what happens [0.2] they go down the the doctor says twenty-four hour 
urine go away [0.5] and er what [0.8] [laughter] and er they take the form away 
[0.3] and then they show it to someone and they go [0.2] oh i don't like this 
and they go oh go and show it to somebody else [0.4] and then they sh-, they 
show it to somebody in the lab and they give you a a p-, a pot with a narrow 
top [0.9] i mean th-, how do you do that [0.4] i mean how do you [0.4] you know 
it's very difficult [0.4] to pee into a narrow neck you know 
'cause they don't give you the other bit of equipment which you need [0.3] 
which is a sort of tray thing to pee into to pour it into the pot [0.7] sorry 
to get so sort of basic on the [1.8] actually i quite like talking about that 
[0.4] [laughter] er [0.7] and er [1.2] it's very difficult to do a twenty-four 
urine but nonetheless it is it is the gold standard test if you can do it 
accurately and it won't miss [0.4] er myeloma [0.2] because [0.2] er it does 
measure other things other than albumin [1.2] okay [0.7] now in the in the last 
er ten or fifteen minutes [0.3] er [0.3] i'm going to talk about 
glomerulonephritis [0.8] er [0.3] now as we've said there are many causes of [0.
2] nephrotic syndrome [0.4] shush [0.5] and there are many causes [0.4] of nep-,
[0.2] of glomerular disease including diabetes [0.6] the thing that gets a 
nephrologist excited is glomerulonephritis [0.6] this is it [0.2] for us we 
love this thing glomerulonephritis it's a long word [0.5] nobody else 
understands it only we 
know we're not going to tell you [1.2] [laughter] we're just not going to tell 
you [0.5] 'cause it's a secret [0.4] and it's why [0.2] people think kidney 
doctors are clever 'cause we can come up with long names like [0.2] type three 
mesangiocapillary glomerulonephritis an obvious case [0.4] can't believe you 
missed it [0.6] [laughter] God [1.1] so obvious [0.4] er [0.5] crescentric 
glomerulonephritis rapidly progressive glomerulonephritis [0.4] that [0.2] for 
us [0.3] is nearly sex [1.2] [laughter] nearly [0.7] crescentic 
glomerulonephritis [0.3] [laughter] oh [0.7] my [0.4] God [0.4] do we get 
excited about it we ring each other up [0.6] [laughter] we [0.3] tell each 
other about it we relive it [1.8] it's great isn't it [0.4] and er [0.8] it er 
[0.3] i only tell you these things because you'll read about them in books 
you'll read five different books they've got six different classifications it's 
all too complicated [1.2] are we stopping there for 
handouts 
nf0600: no i haven't haven't got the page 
nm0572: er [0.6] we we [0.8] we er [1.1] forgot what i'm saying now mid-flow [0.
8] [laughter] talking [0.3] oh i wa-, i was [0.4] talking about rude things i 
was glad you were out of the room [0.4] er [1.4] [laughter] the er [0.8] the 
the we get very excited about these things crescentic glomerulonephritis [0.3] 
er [0.6] all the books are different [0.3] all the classifications are 
different bottom line don't have to know about it [0.7] okay [0.4] so what i'm 
about to tell you in the next ten minutes i-, is purely out of interest [0.7] 
er [0.4] now [1.1] on the handout which you will get [0.6] [laugh] there lists 
[0.2] er seven different groups of types of glomerulonephritis [0.3] and they 
can be largely divided into two groups one of three and one of four [0.5] the 
first group [0.3] the so-called non-proliferative 
glomerulonephritides [0.5] which are usually heavily proteinuric minimal change 
glomerulonephritis [0.7] membranous glomerulonephritis [0.4] and the dreaded F-
S-G-S focal and segmental glomerulosclerosis [1.8] and [0.3] these three 
diseases [0.6] er [0.3] are [0.7] non-proliferative proliferative means there's 
an increase in cell numbers there's no increase in cell number [0.2] if you do 
a renal biopsy in these diseases [0.4] pictures of them in this book and lots 
of other books if you want to see them [0.7] i'm only really going to talk 
about one in much detail today and that's the good one [0.2] if you're going to 
have glomerulonephritis [0.5] have minimal change [0.9] why do you think it's 
called minimal change glomerulonephritis 
sm0603: there's not much change [0.3] 
nm0572: yeah there's not there's no change [0.3] no change [0.4] unlike 
microscopy [1.0] er [0.3] it normally presents in children sometimes in adults 
as [0.2] severe nephrotic syndrome in fact most of these present as nephrotic 
syndrome usually but not always [0.4] in 
kidney medicine anything can present as anything [1.4] and this [0.6] usually 
affects children children [0.9] difficult to do biopsies on them 'cause you 
have to hold them down and parents don't like it tie them up [0.3] parents 
don't like it [0.2] difficult can't anaesthetize them to do a biopsy [0.4] 
parents don't like it [0.2] so so we guess in children [0.3] but i actually 
think it's wrong that we guess [0.3] because i think we make we make er a lot 
of misdiagnoses in children because we don't biopsy them [0.2] if i had my way 
i'd give them [0.2] quick [0.3] quick general anaesthetic [0.2] biopsy much 
much more scientific [0.6] er [0.7] and er [1.4] though i didn't have too much 
problem with that bloke in Liverpool who used to take organs home with him so i 
wouldn't [laughter] wouldn't trust my judgement [0.5] er [0.5] and er [0.8] the 
er it's still not illegal actually what he did was not illegal just a slight 
aside i know it's terrible inappropriate wrong everything like that but it 
wasn't it wasn't and isn't illegal [0.6] er you don't you didn't and don't have 
to ask permission from 
patients to take [0.3] bits of organs out of them [0.4] er the law's going to 
change soon and it will all be illegal and then [1.1] pathology will cease to 
exist [0.3] er [0.2] anyway so minimal change if you if you do a biopsy light 
microscopy is normal [0.7] electron microscopy is abnormal and shows thinning 
of the basement mem-, facement of the podocytes that's the key phrase [0.4] so 
do you remember [0.2] the three layered [0.4] er [0.2] glomerulus [0.3] it's 
the [0.3] epithelium in which there are podocytes they get effaced they in 
other words they get flattened [0.3] that's the key pathological finding [0.6] 
er [0.7] immunofluorescence normal [0.5] er [0.8] self-limiting disease [0.2] 
probably will get better anyway in some children [0.3] er we don't biopsy we 
presume it's that if they nephre-, if they present with nephrotic syndrome 
there's no other obvious cause [0.3] short course of steroids usually goes away 
[0.9] er prednisolone [0.5] er [0.5] in adults it can be a more severe disease 
and some people say 
it's a spectrum of disease that er er which include F-S-G-S [0.5] and [0.3] in 
adults can sometimes require more than steroids we have to use other drugs 
which are cyclophosphamide [0.4] chlorambucil a variety of other drugs [0.8] 
sometimes cyclosporin [0.5] er [0.3] it's quite interesting sometimes in kidney 
medicine we use drugs that we that that we know are the cause of renal disease 
but [0.2] in certain situations that they are of benefit [0.9] and cyclosporin 
is a classic example [0.3] nephrotoxic drug [0.3] but it's been found [0.2] to 
be particularly useful in [0.2] steroid-resistant [0.4] er minimal change in 
adults [1.1] that's got a good prognosis [0.3] that's medium [0.3] er and 
that's terrible [0.6] and er it's part of the reason F-S-G-S is terrible is it 
[0.2] recurs after a kidney transplant [1.1] so don't have s-, F-S-G-S [0.4] 
when i was at an S-R in London Senior Registrar i [0.2] looked after a young 
lady who had had s-, got seven kidneys inside her [0.3] and she was only in her 
early twenties [0.3] she had five transplants all of which had failed 
because of recurrent F-S-G-S [0.8] and i asked her one day whether she wanted 
another transplant and she said oh you might as well i mean i've got er i i've 
got seven might as well have eight [0.7] er [0.8] and er [0.2] anyway [0.4] so 
the other [0.2] er glomerulonephritides the other four [0.8] er [0.3] there's 
the [0.2] so-called [0.4] proliferative in other words there's an increase in 
cell number [0.6] glomerulonephritides [0.5] and are usually less proteinuric 
[0.8] but still have some proteinuria [0.5] er and they are I-G-A nephropathy 
which is probably the commonest of the glomerulonephritides [1.7] er 
mesangiocapillary glomerulonephritis which irritatingly has the same [0.4] er 
eponym as minimal change mesangiocapillary [0.3] in the States called 
membranoproliferative in other countries lobular it's got a variety of other 
names [0.3] it's why in all the books it's got different names 'cause it has 
got different names [0.9] 
post-infectious which we hardly see any more [1.5] related to streptococci 
usually self-limiting disease [0.3] though interestingly it it in books of old 
[0.4] er [0.3] it er if you read if you go into the Wellcome Library on the 
Euston Road read some of the old nephrology books [0.4] er i think the the 
original Bright's disease which were described were probably [0.3] post-
infectious post-strep [0.3] à la rheumatic fever [0.2] à la other [0.4] 
autoimmune complications of infectious diseases [0.3] but i think in in i've 
been in nephrology fourteen years i've only ever seen one person [0.3] with 
post-infectious G-N [0.3] and finally the thing that we love [0.3] crescentric 
[0.3] or some people call it rapidly progressive glomerulonephritis [1.1] that 
usually presents as intermittent macroscopic haematuria in young men that as 
anything [0.2] that as acute renal failure or nephritic syndrome [0.4] that [0.
3] as [0.3] as you can imagine with a 
name like rapidly progressive glomerulonephritis acute renal failure usually [0.
4] er [0.2] associated often with either [0.2] upper airway [0.2] haemorrhage 
[0.2] or lower airway haemorrhage or upper airway haemorrhage [0.3] epistaxis 
[0.2] bleeding out of your ears [0.3] anything upper airway [0.3] and we call 
those sort of diseases Wegener's granulomatosis [0.4] lower airway [0.5] 
pulmonary haemorrhage [0.3] of which there are many causes lupus [0.9] 
polyarthritis so a variety of other causes [0.4] i don't want to go through 
these in any great detail you don't need to know about them in any great detail 
[0.2] what you deed need to know is that they exist and if you think you've got 
one you go and get the cavalry which is [0.4] somebody like us [1.2] er [1.0] 
briefly the thing that we we jump up and down about the thing that we [0.3] er 
[0.3] like so much [0.3] crescentric [0.2] glomerulonephritis [0.7] i'll [0.2] 
talk about for a couple of minutes [0.4] er [0.2] so if you do a 
renal biopsy [0.2] there's lots of bits in the middle the mesangium in the 
middle looks a bit like that [0.3] and in a crescentric glomerulonephritis you 
have a crescent [0.6] of abnormal tissu-, tissue [0.4] hence it's called 
crescentric [0.6] er [1.0] and [0.3] the reason we like it so much is because 
it's a paradigm [0.4] in other words [0.3] it's a disease [0.3] which helps you 
understand other diseases [0.4] and the classic cause of crescentric 
glomerulonephritis of which there are many causes [0.4] is a disease called 
Goodpastures disease [0.5] does anybody know why Goodpasture's disease [0.4] 
being a cause of crescentric G-N [0.3] is a paradigm for other diseases [1.6] 
do you know what i mean by a paradigm it it it's a disease that helps you [1.2] 
understand normal physiology [0.3] and other diseases [2.9] can anybody give me 
a sentence on [0.2] Goodpasture's disease [0.3] 
sm0604: autoimmunity to the basement membrane 
nm0572: yeah very good so it's a disease [0.2] which there is [0.2] an 
autoimmune reaction [0.4] to the basement 
membrane [0.4] both in the kidney [0.6] and in the lung [0.9] the same antibody 
is directed towards the glomerular basement membrane in the kidney and the lung 
[1.2] and [0.2] you can actually prove this you can measure the level of this 
antibody in the blood [0.4] when you have somebody and they usually present 
with a combination of acute renal failure and pulmonary haemorrhage [1.0] 
usually on a Friday afternoon [laughter] for some strange reason [0.5] and er 
[0.4] actually i think the only reason things occur [0.3] on a Friday afternoon 
why do you think things are referred to specialist units on a Friday afternoon 
[0.5] do diseases really happen [0.6] more commonly on a Friday afternoon 
ss: 
nm0572: speak up [0.4] 
sf0605: G-Ps don't want to get called out on the weekends [laughter] 
nm0572: very good yeah i'm a cynic ah i know [0.9] er yeah G-Ps don't want to 
get called out at weekends [0.2] also some hospital doctors [0.4] er [0.4] sit 
on their arses all week go to the mess [0.4] er sit around pontificate [0.2] 
now 
bloody hell Thursday all the oh bad blood tests [0.5] i'd better tell somebody 
oh i'll do it tomorrow Friday comes [0.4] tell everybody's [squawk] [0.3] er 
send them to the renal unit or the cardiac unit just get them out of there get 
them out of Nuneaton [0.3] get them out of your small hospital [0.3] and get 
them to the teaching centre [0.2] so it's actually [0.5] ho-, teaching hospital 
doctors always moan about Friday afternoons there are [0.2] there are reasons 
why things happen on a Friday i think it's people [0.5] er clearing the rubbish 
out [0.2] [laughter] before you go go all go off for the weekend [1.3] er [0.4] 
and er [0.6] so the reason it's a paradigm is you can measure and prove the 
autoantibodies in the blood you can also do [0.2] biopsies of both the lung and 
the kidney and use immunofluorescent techniques [0.4] and [0.2] show up these 
autoantibodies [0.3] er to glomerular basement membrane and they're very pretty 
[0.9] the other reason why it's a paradigm [0.3] er is you've got a disease [0.
4] autoimmunity [0.5] antibody in the 
right place in the blood in the kidney in the lung [0.3] and you suppress the 
immune system with a combination of methylprednisolone [0.2] cyclophosphamide 
and plasma exchange [0.5] and they get better [1.0] magic [0.4] all the 
antibody goes away [0.3] you can repeat the biopsy at the end but it's gone the 
levels go down in the blood the patient gets better [0.6] er [0.5] obviously 
it's not as simple as that we don't really understand [0.4] the cause of [0.9] 
Goodpasture's disease or how the causes [0.7] does the damage and whether these 
autoantibodies are [0.2] are truly pathological [0.2] or are they innocent 
bystanders are they drawn in by some other cytokines or something like that [0.
4] but either way they're there [0.7] er [0.3] and they go away [0.2] if you 
immunosuppress the patient [1.5] okay [0.2] so that's a brief run-through of 
glomerulonephritis [0.3] from a a a a 
non er pathological perspective if you're interested [0.3] the books are out 
there the web sites are out there [0.5] er [0.4] i don't suggest don't rustle 
your papers yet hold on wait for it [0.6] er [1.4] i suggest you know [0.4] a 
reasonable amount of minimal change nephropathy partly when you do paediatrics 
[0.4] er they'll be talking a lot about minimal change nephropathy [0.4] er i 
suggest you do some reading [0.3] er [0.2] on the other forms of 
glomerulonephritis not particularly for your exams [0.3] but but just [0.3] er 
for your own interest and also to make you aware of how different all the books 
are [0.2] in terms of glomerulonephritis [0.4] and i would do some reading 
about crescentric G-N 'cause [0.2] there are a lot of things you can learn [0.
3] about the working of the [0.2] immune system and autoimmunity [0.2] if you 
understand crescentric G-N [0.9] okay that's it any questions on [0.8] 
nephrotic syndrome glomerular disease [0.2] glomerulonephritis [2.0] or anything