nf0369: right [0.7] okay [1.1] if we can settle down we need to [0.3] dash on 
to the next one [12.0] now again some of this is going to be [0.3] revision for 
you [0.8] because er we touched upon it briefly in musculoskeletal [0.4] er [0.
4] that was last semester i think wasn't it [0.8] and [0.3] it comes up again 
in clinical pharmacology when we look at bone diseases [1.6] so it's partly 
revision but we're looking at it from a different aspect today [0.6] so i just 
want to have a look at what [0.4] what's normal [0.6] a very quick review of 
calcium homeostasis [1.3] er look at the tissues that are involved but 
obviously particularly the kidney the kidney's what we're really talking about 
today so although there's a multitude of tissues involved in calcium 
homeostasis [0.5] the kidney's the one i'm concentrating on [0.9] and then have 
a quick look at vitamin D deficiency [0.6] er [1.0] because that's really 
important when we're considering renal disease [1.8] so if we look at the 
physiological roles of [0.2] calcium [0.7] we went over this last semester [0.
5] and in that time we were particularly talking 
about [0.2] bones [0.5] and we're going to be tic-, particularly talking about 
bones in clinical pharmacology [2.2] that obviously is a long term effect [0.3] 
calcium homeostasis [0.3] gone wrong [0.6] will affect bones but it has a 
longer term [0.5] er effect it's not going to happen overnight [0.5] although 
you can see changes within a fortnight but i-, it's a long process more chronic 
[0.8] whereas these functions that i've listed here [0.5] are much more rapid 
and acute [0.6] er in terms of the functions of the calcium [0.4] obviously if 
you have changes in your nerve function and nerve signalling [0.5] er or muscle 
contraction [0.4] that'll happen rapidly [0.5] so there are sort of kind of 
acute and chronic [0.2] consequences of calcium homeostasis being messed up [0.
8] and this one i've just put here just to remind you [0.4] er that one of the 
roles of calcium is in er blood clotting [0.4] so if you've all your blood 
tubes or a lot of them have er E-D-T-A in that's simply to collate the calcium 
and stop the blood that you've taken clotting so that's why E-D-T-A's [0.5] in 
blood tubes [0.8] but 
the really important thing is that the levels need to be very tightly regulated 
[0.5] in order to ensure that all these kind of acute problems don't happen [0.
4] and then longer term the chronic bone problems you need to regulate your 
calcium levels that are circulating quite closely [1.6] so this is a slide 
you've had this one before [0.4] but just to remind you [0.3] these are the 
plasma concentrations [0.4] and this is the normal range here or roughly [0.7] 
now these numbers that i've put up and the numbers that i've put up on a lot of 
my slides [0.3] depending on the book you look at they will vary very slightly 
[0.9] i've got forty-five per cent ionized here and fifty-five per cent bound 
[0.4] what i tend to do in my numbers is trying to match [0.3] what the namex 
students get [0.3] but you will find books that'll give you anywhere between 
forty and fifty here er and alter this accordingly [0.6] it doesn't matter too 
much again it's roughly fifty-fifty [0.5] er [0.4] but i'll give you the 
numbers as [0.2] best i can as er to match namex's but 
just bear in mind thes-, they're not absolute values [0.4] so this is your 
normal plasma concentration [0.4] that's the range and it's split like this [0.
4] and this is important because it's only the ionized calcium [0.3] that 
actually has an effect [0.4] what you're really interested in is the amount of 
ionized calcium that's free in the blood [0.4] or in the plasma [0.6] not the 
calcium that is bound [0.6] although that has a role to play obviously it's a 
storage component [0.5] and the flux between bound and [0.3] and free is really 
important [0.4] and there are issues there [0.5] in terms of physical function 
it's the ionized calcium that has a role [1.4] but in terms of the kidney it's 
important to note this is further subdivided you've got some of it bound to 
plasma proteins [0.3] and this is predominantly albumin [0.3] and you'll see 
that's important in a minute [0.6] er but some of it's ions so anions you've 
got bicarb and phosphate and citrate [1.3] er [0.3] and that's important 
because these get into the kidney [0.8] but er [1.2] forty-five per cent is 
bound to 
proteins and can't be filtered [0.9] and this is what we need again figures 
i've given you already you need a gram if you're a normal person [0.6] if 
you're pregnant or lactating you need a bit more because obviously you're 
building up the bones in the child and you need to make milk so you need more 
calcium [0.5] and if you're old you need more [0.4] and you need more if you're 
old because you can't absorb it from your gut [0.3] as efficiently [0.7] so 
although you're taking in more as an elderly person your absorption from the 
gut [0.3] is decreased so your actual er [0.6] levels usually they're they're 
deficient elderly people in calcium from what we would normally [0.3] count as 
normal levels [2.3] so if we look at plasma concentrations or plasma calcium [0.
4] that's what i've told you [0.5] that's what we're really interested in 
regulating is the free calcium [1.2] when you send blood off to a lab [0.4] 
it'll send it back as a total calcium concentration you'll get [0.4] two-point-
four or two-point-five or whatever it back as as 
a number [0.5] and that's your total calcium concentration [0.5] and what 
they've done is they've corrected for albumin [0.6] now okay don't get tied up 
this is exactly what happens [0.5] er the calculation that's used but you can 
see they measure the the blood albumin [0.3] as well as the blood calcium [0.9] 
now this is taken something that any of you going into renal [0.2] fields will 
find out about there's a renal registry [0.5] renal medicine's quite tightly 
controlled in Britain [0.4] and er they produce a renal registry which outlines 
er [0.3] treatment standards how quickly you should be seen if you've got 
various conditions [0.4] what your [0.3] concentrations of various things 
should be et cetera it's standardized throughout the country [0.4] and they 
also list things like [0.3] how the measurements are done in different 
hospitals because calcium and albumin are measured differently [0.4] depending 
on which hospital you're working in so there's different there's about three or 
four assays for them [0.5] different hospitals use different ones [0.6] and as 
a consequence [0.3] this correction equation [0.3] will vary between hospitals 
[0.5] now this is kind of like the U-K standard in the renal registry [0.5] if 
you measure the calcium the way they suggest and the albumin the way they 
suggest [0.3] then this is the equation they would use [0.5] however the 
Walsgrave [0.4] just uses a completely different formula it's slightly more 
complicated so if you see the correction from the Walsgrave from labs [0.3] and 
it's different to this [0.3] this is why [0.4] but you don't need to know it 
all you need to know is that you're getting back the total calcium [0.6] and 
that's important because it can skew your results [1.0] you normally know [0.3] 
if it's a total calcium and they've corrected for albumin [0.3] in a normal 
person that's fine [0.4] er it's going to be split in a forty-five fifty-five 
proportions so you know roughly what your free albumin is [0.4] er free calcium 
whether normal or not [0.8] if somebody has a disease or a condition where 
their albumin levels [0.3] are grossly abnormal [0.4] that may skew the results 
[0.4] so for 
example if somebody has a very low albumin [0.4] it may come back er [0.4] the 
total may be [0.2] normal [0.4] but actually the amount you've got bound 
because your albumin's low [0.4] is low so your free calcium could be 
significantly higher than you would [0.3] normally expect [0.5] so this happens 
with a couple of er [0.7] er [0.5] substances that you [0.2] do lab 
measurements on [0.3] so just bear in mind your total calcium [0.4] may not a 
normal total calcium may not reflect a normal [0.4] total er free calcium and 
sometimes you have to bear that in mind [1.3] i've put here can we measure free 
[0.2] we said you were interested in free why don't we measure free [0.7] it's 
more difficult is the simple answer [0.6] the assays are more variable between 
places and people are [0.6] er [0.3] seem to be very divided over this as to 
whether it actually gives you any great benefit in the average person [0.3] if 
you think there's a reason why you need free particularly for that patient you 
might want to request it [0.3] but on the whole [0.3] people think for the time 
money and the variability it 
doesn't seem to be worth [0.5] er it doesn't give you a significantly better 
result [1.1] and i've just put this here [0.6] this is very low remember most 
of the calcium [0.2] isn't within a cell [0.2] and the calcium that is in a 
cell [0.3] is complexed to calmodulin and you must keep it very low [0.5] so er 
[0.3] that's just something to bear in mind that calcium normally is not in 
cells at all [1.0] so what happens when it goes wrong [1.4] obviously you can 
have too much or too little [0.6] so [0.2] if we look at hypocalcaemia first [0.
7] generally [0.3] and this is a big generalization this tends to be the more 
serious condition because it tends to be more acute [0.6] and that's a big 
they're they're generalizations [0.4] but you'll see from the hypercalcaemia 
slide [0.7] on the whole it has more chronic er less severe effects [0.9] if 
you haven't got enough calcium [0.4] it really affects your nerves and er your 
signalling [0.3] and the muscle function and you get er muscle cramps and 
tetany [0.7] and long term seizures [0.4] and most of you will be aware of 
tetany but it's quite [0.3] clear to see 
here in a wrist you see it in other er [0.9] er [0.7] tissues but the the wrist 
and the hand are quite normal and that's the er form that it takes basically [0.
3] you're unable your muscles are er contracted and you're unable to [0.8] 
uncontract them [0.2] for want of a better word [0.5] er [0.3] and that's a 
symptom of low calcium [0.5] but this is what's important [0.4] you get cardiac 
arrhythmias [0.8] and then if we look at hypercalcaemia [0.2] in the contrast 
[0.6] this tends to i said it tends to be slight and variable [0.6] a lot of 
cases of hypercalcaemia are picked up on routine blood scans [0.2] er tests [0.
4] so normally it sort of often occurs middle-aged women they go for a Well wom-
, Well Women Clinic or Well Woman Clinic [0.5] have a blood sample they measure 
calcium and find their calcium's quite high [0.2] it is a consequence the 
symptoms [0.2] obviously er are quite minor so [0.4] you've got a ole-, whole 
range of G-I kind of problems [0.4] they can be a bit depressed tired confused 
[0.4] but as this is normally a er disease of middle-aged women [0.3] er [0.2] 
because they 
often have a parathyroid hormone tumour which we'll see about in a bit [0.5] 
these sort of symptoms are very similar to menopause type symptoms so you 
wouldn't really [0.3] er pick up on them [0.4] muscle weakness [0.6] this is [0.
2] a big one [0.7] if it goes on for a long time [0.3] or you're severely 
hypercalcaemic and you've got far too much calcium [0.3] the calcium will 
deposit [0.4] and form er solid lumps [0.3] and this either happens in the 
kidney and forms kidney stones which we'll see about in the next session [0.4] 
stones aren't only made of calcium there's lots of different types of stones [0.
4] but some of them are made of calcium [0.4] and you get ectopic calcification 
[0.4] so you can pick up little lumps of calcium on X-rays [0.3] in all sorts 
of places where you wouldn't expect them throughout the kidneys [0.3] or 
throughout the body [0.3] so if it goes on for a long long time you're severely 
hypercalcaemic that's a problem [1.0] but again [0.5] very hypercalcaemic [0.7] 
very suddenly [0.3] and you have cardiac problems again [1.0] so that's why 
it's really 
important if it's an acute [0.4] er situation [0.7] so what do you do the main 
aims [0.4] if you've got a patient is you want to normalize their calcium [1.4] 
so if they're hypercalcaemic and i've just put here [0.4] if their levels 
remember the normal's about two-point-five if the levels are up here [0.3] it's 
an emergency in terms of heart conditions [0.6] er [0.2] so what you do is you 
try to flush the calcium out of the system by giving them fluids and making 
them pee more [0.6] and these treatments here basically refer to the bone 
conditions [0.4] because [0.3] if you're hypercalcaemic [0.3] most of that 
calcium's coming from your bone if you remember i told you that in the second 
year and we'll look at that [0.4] er second semester and we'll look at that in 
a couple of weeks' time [0.5] so if you can stop the bones losing calcium that 
will help bring down the calcium level certainly long term [0.4] so these are a 
more longer term treatment and they affect the bone [0.4] but initially you're 
going to want to try and flush the calcium certainly flush it 
out of the system [1.3] and as i said normally it's a parathyroid tumour [0.5] 
er ninety per cent of the cases unless they're an emergency if it's a chronic 
hypercalcaemia [0.4] are parathyroid tumours [0.4] and then you may have to 
consider removing all or some of the parathyroid glands [2.2] if it's hypercal-,
hypocalcaemia sorry hypo [0.7] again you've got an acute situation or a 
chronic [0.6] if it's acute you can simply give them calcium I-V [0.4] and you 
give them that as er [0.3] calcium gluconate [0.6] if it's chronic [0.5] you 
want to make certain they've got enough calcium in their diet [0.3] and they're 
able to reabsorb it or absorb it from their diet properly [0.4] so you give 
them calcium [0.3] and give them vitamin D and we'll see why they need vitamin 
D [0.2] a little later [1.0] and i've just put this in P-T-H-R-P [0.4] it's 
nothing to do with the kidney really or at least not that we know of at the 
moment [0.6] but because it acts exactly like parathyroid hormone [0.3] and 
we'll see the effects of that in a couple of slides [0.3] it can make people 
hypercalcaemic [0.4] so [0.2] but if often occurs when there's malignancy [0.5] 
so hypercalcaemia and malignancy tend to go hand in hand [0.4] and although 
there's a number of causes for that [0.4] increased P-T-H-R-P can be one of 
them [0.4] so you just bear in mind you you may need to look for this [0.9] er 
the difference is [0.4] er if you've got er [0.2] hyperparathyroidism it won't 
affect your P-T-H-R-P production [0.6] and likewise er [0.4] you don't see a 
change in your vitamin D levels so if your vitamin D levels are normal [0.3] 
but very high calcium [0.5] er and you haven't got a parathyroid tumour it 
might be worth looking for a tumour elsewhere that's producing P-T-H-R-P [1.7] 
so this is the slide i've shown you before [0.5] low calcium [0.4] you produce 
P-T-H that affects the bone [0.2] and the kidney [0.4] the kidney produces 
vitamin D [1.5] which acts on the bone and the gut and the net effects are 
increased calcium and feedback to switch the whole system off [0.4] and i've 
put the kidney in the middle [0.4] not because i think it's the most important 
but it is quite pivotal to 
this system [1.1] and if we're looking at calcium homeostasis and the kidney [0.
3] it's basically got three roles [0.7] phosphate i've put here because 
phosphate and calcium go hand in hand one goes up the other goes down and we've 
[0.4] talked about that and that's more apparent in the bone lectures [0.6] er 
so we're not going to discuss it today [0.5] but the other thing it does is it 
regulates your reabsorption from your filtrate you filter all your calcium more 
or less [0.3] into your filtrate [0.3] and you want to reabsorb most of it or 
regulate how much of that you reabsorb [0.4] so the regulation of reabsorption 
from the filtrate or the occurrence of it [0.3] happens in the kidney [0.6] and 
it makes vitamin D and vitamin D [0.3] is really important for calcium 
homeostasis [1.0] so if we look at this [0.5] er your filtered calcium again [0.
6] takes all the free calcium but it also takes the calcium that's bound to the 
anions [0.3] not the protein-bound [0.2] calcium because obviously that can't 
be filtered through if it's bound to a protein [0.4] but it does take the 
ionic bound so you've got about fifty-five per cent getting into the filtrate 
[0.8] and this is roughly what happens as you go across the nephron so here's a 
schematic nephron [0.5] and this indicates your calcium concentrations as you 
go through [0.4] so by the time you get into the thin [0.6] descending loop of 
Henle nearly all of your calcium's been reabsorbed already [0.4] and most of it 
happens here [0.4] and you've got a little bit left to be reabsorbed [0.2] 
throughout this part of the nephron [1.0] so if we put that in context [0.4] 
you've got at least sixty seventy per cent of your calcium's reabsorbed in the 
proximal tubule [0.7] most of that happens by simple diffusion [0.4] but there 
is some active transport [0.2] but we're not going to look at that in great 
detail [1.7] when we come down here we've got the er loop of Henle between it 
you get a bit more reabsorbed [0.6] and the distal convoluted tubule now this 
is interesting because although it's only a small proportion that's reabsorbed 
here [0.5] this is under active transport and is 
regulated [0.4] so this is where the P-T-H has a role it can regulate the 
amount of calcium reabsorbed here [0.4] but you can see you're only talking of 
regulating a very small proportion so it's [0.3] quite a fine tuning exercise 
in terms of maintaining your calcium levels [0.4] er from your kidneys [0.5] 
and then a little bit goes into the collecting duct [0.3] and [0.4] only a 
small per cent out in urine one to two per cent in urine [0.4] and you can see 
here you filter this much er per day [0.3] but you reabsorb ninety-eight ninety-
nine per cent of that [0.6] so the kidney's really important if it stops 
reabsorbing calcium [0.4] for any reason you're going to lose your calcium 
really rapidly [1.2] so what about vitamin D i said the kidney makes vitamin D 
[0.3] and the reason it's really important in terms of er [0.6] calcium apart 
from the bones is that it regulates the uptake from the gut [0.5] so i'm going 
to er go through this quite quickly 'cause it's not a G-I lecture but [0.5] 
you've got three ways you can take up calcium from the gut [0.4] simple [0.3] 
er transport 
between cells [1.2] secondly it gets absorbed in the brush border binds to 
binding proteins and then is extruded by this er [0.5] A-T-P-ase [1.4] also it 
goes across the brush border goes into vesicles [0.3] and then er endocytosis 
gets rid of it at this end [0.3] but the important thing to note is that [0.3] 
er [0.2] the calcium binding protein is involved in all three cases doesn't 
matter which mechanism's used you need a calcium binding protein [0.4] to get 
it across the cell [0.6] and this is regulated by vitamin D [0.5] so vitamin D 
increases levels of calcium binding protein [0.6] which will effectively allow 
you to take up more from your gut [0.3] it also alters the permeability of the 
brush border [0.5] er so it allows more [0.3] er calcium to be [0.2] er [0.2] 
absorbed through the brush border of the G-I system [0.5] and vitamin D has got 
some role to play in this regulation of the calcium-sodium exchanger [0.5] so 
vitamin D regulates the calcium from your diet [1.4] it also is important for 
bones we've talked about this before and we're going to [0.3] so whether the 
calcium stays in your bones or is released in the circulation vitamin D has a 
role in [0.7] and er [0.6] it also regulates er you know when i said P-T-H 
regulates that small amount of er [0.2] calcium reabsorbed in the [0.2] the gut 
[0.6] er [0.7] vitamin D will also regulate calcium absorption to a small 
amount [0.6] but its real importance is regulating bone [0.3] and regulating 
calcium uptake from the gut [0.7] so how do we make vitamin D and this is 
really important in terms of kidneys [0.5] so sunlight produces [0.5] somewhere 
between eighty and ninety per cent of our vitamin D in our sun that's why it's 
important to get some sunlight [0.5] er [0.2] while balancing that against the 
risk of skin cancer [1.0] er we get some from our diet and here here the levels 
of bile salts have a role to play but again that's that's a topic beyond the 
urinary course [0.7] and the liver activates both these precursor forms [0.3] 
into twenty-five-hydroxy-vitamin-D-three which is largely inactive [0.4] and 
you can store that for quite a long time [0.6] and then the kidney [0.4] here 
has 
another enzyme that activates it into the active form which is one-twenty-five- 
[0.3] dihydroxy-vitamin-D-three [0.5] and as clinicians you'll get used to 
calling it calcitriol [0.8] i try and use that but i i tend to use its real 
name 'cause obviously that's what i use in research all the time [0.6] and 
these are the two enzymes that are involved [0.5] they're both hydroxylases the 
liver has twenty-five-hydroxylase [0.3] and the kidney has one-alpha-
hydroxylase [0.3] it's got a much longer name but that'll do for you [0.7] this 
one er is not regulated and depends on substrate concentrations [0.5] this one 
is very tightly regulated so you can see defects in either the liver [0.3] or 
the kidney [0.3] will affect your ability to make vitamin D [2.7] so what's 
important [0.3] i've just told you that the activity of the twenty-five-
hydroxylase isn't regulated [0.4] so if you want to see if somebody is 
deficient in vitamin D or not [0.3] you can measure the twenty-five-hydroxy-
vitamin-D-three levels the circulating substrate form [0.5] and that'll tell 
you [0.4] er [0.4] their vitamin 
D status [0.3] [2.6] the one-alpha-hydroxylase conversely [0.3] very tightly 
regulated only works when you need the active form of vitamin D [0.5] and 
that's because [0.3] the vitamin d-, the active form of vitamin D [0.3] is so 
good at [0.4] er [0.3] increasing levels of calcium in your blood [0.3] if you 
have too much active vitamin D you become hypercalcaemic [0.4] very rapidly [0.
5] and i do touch on this very briefly in the clinical pharmacology lecture [0.
8] er [0.8] so it's very tightly regulated and i've just put here [0.3] all the 
textbooks will tell you it's only in the kidney [0.4] absolute rubbish couple 
of years ago we found out that this enzyme now [0.6] all the tissues more or 
less in the body not [0.3] not every single one but the vast majority are able 
to make vitamin D [0.4] don't know why yet [0.3] and we don't know what 
regulates it yet but er [0.9] five years down the line textbooks will be 
different [0.9] and that's just the normal ranges for your information i'm not 
going to dwell on that but you can see you've got far greater amounts of twenty-
five versus 
one-twenty-five-D-three [1.8] so what happens why is the kidney important [0.4] 
apart from regulating the levels of calcium in your blood [0.4] er people with 
kidney disease can't make vitamin D [1.3] that's sometimes because their 
kidneys are not functioning at all er they have no effect whatsoever but if the 
kidneys are just not working quite as well as normal [0.3] then their ability 
to make vitamin D will be attenuated [0.4] [1.3] if they can't make vitamin D 
[0.3] obviously they become vitamin D deficient [0.4] you don't absorb calcium 
from your gut [0.5] you don't reabsorb it from your bone and you become 
hypocalcaemic [0.6] this then activates the parathyroid glands to produce P-T-H 
[0.8] the P-T-H [0.6] then [0.7] will act on bone to release calcium [0.5] but 
it will also try and act on the kidney to stimulate vitamin D production [0.2] 
but remember your kidneys are knackered for one reason or another [0.4] so the 
vitamin D production doesn't go up [0.7] so you're still hypocalcaemic [0.2] 
because there's no vitamin D [0.4] so the only place the P-T-H can act is on 
the bone [0.6] so 
the bone P-T-H system kind of goes into overdrive [0.3] you reabsorb more and 
more and more bone to try and normalize your calcium levels [0.4] the 
consequences are [0.5] you get really bad bone disease [0.8] er [1.2] and that 
[0.2] if it's caused because of er [0.2] kidney disease it's known as renal 
osteodystrophy [0.4] in terms of phenotype it's very similar to osteoporosis [0.
6] er and this is a real problem [0.4] this secondary hyperparathyroidism [0.5] 
so the the [0.3] parathyroid glands [0.3] don't switch off 'cause there's no 
vitamin D to act as a negative feedback [0.5] it's almost impossible to 
normalize your calcium plasma calcium levels [0.3] so that doesn't feed back to 
switch off P-T-H production [0.3] and the gland goes into overdrive producing 
more and more P-T-H [0.3] which only acts on the bone [0.4] so you get severe 
bone disease [0.4] and this is a real problem with anybody with renal disease 
[0.9] so these are the things to take home this is revision [0.7] calcium 
homeostasis basically you've got three main hormones we haven't talked about 
calcitonin today [0.4] i'll do 
in a couple of weeks [0.5] and er [0.6] three tissues [0.3] er four tissues 
sorry you've got gut and bone put there together [0.4] so four tissues three 
hormones [0.9] this is important to remember later in the the module doesn't 
come up now [0.5] but the most of the calcium that you eat [0.4] we excrete [0.
6] whereas nearly all of the phosphate that you ingest [0.2] we retain [0.8] er 
or you absorb rather you don't [0.2] retain it you absorb it so when you're 
looking at the [0.2] G-I uptake [0.4] most calcium [0.5] is excreted 
straightaway in faeces whereas all the phosphate is absorbed [0.3] and that 
will become apparent why that's important later on [1.2] okay so the kidney's 
important 'cause it reabsorbs most of the filtered calcium and makes vitamin D 
[0.7] and vitamin D we've just gone over [1.5] a hyperparathyroidism [1.0] now 
this is er [0.5] something that comes up in the group work and something you'll 
get used to [0.4] as you go through the module [0.8] but there's three forms of 
hyperparathyroidism [0.8] now remember i said most er [0.2] hypercalcaemia 
presents with a sort of middle-aged 
woman [0.5] er in a routine blood test and she's probably got a tumour [0.9] 
now that's primary hyperparathyroidism [0.4] the parathyroid glands [0.3] are 
producing too much P-T-H on their own [0.9] now in that case [0.4] you have er 
[0.4] too much P-T-H [0.4] the kidneys respond normally producing more vitamin 
D [0.5] er the bones respond to release calcium [1.1] that all produces an 
increase in calcium in the plasma [0.4] but because it's coming from a tumour 
there's no negative feedback system working [0.6] so you go on and on [0.2] 
producing more calcium [0.5] er hence hypercalcaemia [1.2] and that's [0.2] 
relatively simple you can whip some of the parathyroids out [2.1] secondary 
hyperparathyroidism was the one we've just talked about where the system can't 
work [0.4] so there's no negative feedback so the parathyroid glands go on 
producing [0.4] er P-T-H [0.5] and eventually they er become desensitized as 
we'll see [0.7] now this is i've put vitamin D deficiency here but it's usually 
is a consequence of renal disease it's not somebody who's just not [0.5] er [0.
4] vitamin D deficient 
and developing rickets it's a renal problem really [0.5] and in that case 
you've got low or normal plasma calcium whereas they're high here [1.0] and the 
last one is tertiary hyperparathyroidism [0.4] and this is really quite 
specialized [0.5] er this is a er [0.6] consequence of renal disease [0.6] but 
it's a er [0.2] a continuation of secondary hyperparathyroidism [0.6] when 
there's no feedback [0.3] er to switch the parathyroid glands off they go on 
producing P-T-H [0.6] and they become insensitive to calcium levels and vitamin 
D the receptor levels drop [0.6] they also sometimes become hyperplastic so you 
get more cells [0.4] er bigger parathyroid glands [0.3] producing more P-T-H [0.
4] so the consequences are completely unregulated P-T-H production [0.6] 
remember you've got kidneys that can't respond normally [0.6] er [0.4] so you 
get er [0.2] loads and loads and loads of reabsorption from your bone so you 
get really bad bone disease [0.3] but in that case as well you usually 
have high plasma calcium [0.7] but [0.2] this h-, plasma calcium which would 
normally shut off P-T-H production can't because the gland's lost all its 
natural [0.5] er [0.5] mechanisms for feedback [1.7] oh i'll leave that slide 
up at the end in a minute 'cause i realize you haven't got that one 'cause that 
was an addition [0.6] this one at the end i'm not going through it's kind of a 
pictorial representation of secondary hyperparathyroidism [0.5] and the 
problems associated with kidney disease [0.6] it's er [0.3] it's really 
important you know calcium homeostasis er goes up the creek if you've kidney 
disease [0.7] so that's all i've got to say now er [0.4] 'cause i know we're 
running slightly probably any questions either come and see me or see me in the 
group work [0.5] and er i'll just leave that one up for you to copy down [0.4] 
while i get namex sorted out for the next lecture