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