A United States Army Medical Department,
continuing Education program,
morphology of recurrent disease and
transplantation
with James D Mullin's major US Air Force Medical
Corps,
Wilford Hall,
US Air Force Medical Center,
Lackland Air Force Base.
Just real quick.
I'd like to go back through again.
What he's talking about when you get some pathological change and more
likely to change in the of a graph or several things you do have to
consider.
Number one is transmission arts,
the existence of transmission I don't think can really
be argued if you go back and look at the experience of Peter
when they transplant the ISS identical twins,
which there really should be no reason for uh any
type of his incompatibility.
17 of the 22 patients in an iso study
had the I
when they reviewed the his in the history,
it felt that 17 to 22 had courses
consistent with native arthritis.
All for E M work really wasn't done.
I got 17 which was felt to have native
uh or native kidney.
11 reoccurred with morphological changes of
arthritis and all that 11,
either six or seven went on to lose their graft,
all their life because of the to arthritis.
So transplant,
I mean transmission does exist at least in
the has been well described and the
autograph becomes much harder problem because here you run into the
problem,
the changes you see in the autograph immunity,
the rejection process itself.
Plus there's another very important difference between this is
series and the autograph series.
I mean nobody in this country,
I am in Europe.
Sometimes they will give autographs withhold imm
suppression and H L A identical grasp in this country.
Everybody with an autograph gets immuno suppression.
And that obviously is gonna have some influence on the
morphological and clinical expression of the transmission of
arthritis.
That is group.
Only three of those people were treated prophylactically with uh
immunosuppression for at least for the clinicians,
maybe make you feel happier.
It seems like at least if you start these people on
immunosuppression,
right.
As soon as they get the kidney,
you appear to uh at least delay or
modify the transmission of arthritis from what we can
tell.
And most people that lose their kidneys and our experience and I think
everybody else's experience lose their kidney through the
process of rejection.
Whether or not to have some degree of recurrence of
arthritis or not,
it seems to be minor except in a few instances in which I'll talk
about and rejection,
usually what gets the graft and
there's other things that can cause morphological changes in the graph
alluded to the Pacific auto
autograph immunity.
There's no reason that you couldn't form uh circulating H L
A anti H L A antibodies.
And if we're talking about in a minute,
it's not uncommon to see deposits and
graphs who did not have native
arthritis.
And maybe this is an example of a uh autograph
immunity with immune complex disease.
Like you see with some other instances and
also the ischemic change you get in to cloud the
picture somewhat.
The pacific instance in which transmission arthritis
is a real problem are focal sclerosing
opathy.
Again,
I use that you really shouldn't even call it a arthritis.
But we're going to put it in there anyway,
because it's really not an inflammatory process but whether it's
inflammatory or not,
it destroys kidneys.
This is a lady.
Doctor mcfall was talking about,
this is uh a patient of ours had about a
three year history of Nephritic syndrome went into
slowly progressive renal failure.
We went back and looked at her original kidneys and some
original biopsies.
And what we saw was classic focus grows and
the process was focal and segmental.
Here,
you can see the loop looks pretty good,
but you will notice going on here,
there's completely hypo cellar area,
s matrix proliferation,
adhesion to bone capsule.
Here you can see some high
drop at seven deposits and
foam cells.
A classic his focus and the
plus on E M,
she showed the fusion of foot processes which is the other
component of this disease.
This is just a higher P an area of focal
sclerosis.
You can see this part of the loop looks pretty good.
This is the P A S stain.
These sub inter deposits are highland
deposits stand out very nicely.
This is not me matrix.
It does not have a fibular mass matrix and on
silver stain,
this material does not stain silver positive like Messan matrix.
The deposits on E E M correspond to seven or three
electron dense deposits.
The exact nature of which nobody should.
This is an E M on a patient with and,
and from looking at this one field,
it's identical to what you see in Neil's disease.
An opinion of many people who have a lot more experience with E M than I
do like doctors Fargo uh
feel that the presence of diffuse fusion of foot
process is approaching 100% is really found
only in two disease entity,
no matter whether there's neurotic syndrome present or not.
That's Neal's disease and go
what the relationship of and is to Neil's
disease is unknown as a subject unto itself.
This is an example of this lady's graph when it had
to be removed at approximately two months.
Although she had normal renal function,
she had such a horrendous nephritic syndrome.
But clinically,
the graph had to be removed for the benefit of the patient.
Here.
Again,
you can see the reoccurrence,
this peculiar
sclerosis here with some adhesions to Bowman's capsule.
Here.
When you're talking about foot process fusion in the graph,
it comes a little different.
You can get significant fusion of foot process and autograph
rejection.
But at least in Bush's experience in the porters
usually doesn't go beyond 70%.
The Nero syndromes associated with chronic
rejection again,
show diffuse fusion of foot processes,
but they get a massive change in the sub endothelial on
the basement membrane,
which I talked about with you before.
So this lady is showing diffuse fusion of foot
processes 100% without sub endothelial
changes in her basement membrane.
And even though this is in a graph,
I think it's a still pat of focus
on E M.
And then when you combine it with a light,
my there's really no doubt.
And this is just her most recent graph again showing a re
occurrence that peculiar focus crossing.
Fortunately,
this time,
she's not having near as much and she's able to uh
maintain useful function.
Despite the syndrome,
the other entity in which you can see recurrence of
is fairly commonly.
I think the only real big series out of Minnesota five of
nine Children with so called me
has also been called hyper of
childhood reoccurred with the disease.
And they usually show recurrence of the hyper
aia too if they recur with the disease in the ground.
The patient of Doctor mcfall talked about priest.
I really don't have any good slides on,
I took some slides,
but unfortunately,
uh they didn't turn out very well.
But I will show you some examples of me my
in a native kidney,
some people use the term very loosely.
We use a very strict sense and it is a disease in which
you get massive with beginning
libation,
massive enlargement of the.
As you see,
here are 2 to 3 times normal size and some degree
of thickening the basement membrane,
which may or may not show splitting.
This is another example of me,
you see the mark lobulation,
increased massage matrix.
And as you can appreciate here,
this one here is the type that's showing the
splitting of the basement membrane due to massage in
position.
Here you can see the splitting of the basement
membrane.
Now,
when this disease reoccurs in the graph,
just the presence of splitting the basement membrane is not significant to
make it uh sufficient to make a diagnosed meno poly
circumferential mas inter position is very common in
graphs.
I'm sorry,
I didn't get through to the ems this morning on the graph changes.
After you get that change,
the next change you can go into is a
circumferential masang inter position and chronic graph
rejection.
So you've got to see the overall changes it should be marketed,
enlargement of the the prominent
lobulation as well as the basement membrane changer before you
can make a diagnosis of current me
in contrast to the sang and peripheral basement
membrane change,
you can get in just chronic vascular rejection without
any underlying immunological problem.
Now,
this is an example of me Riis
here is the original basement membrane here here would
be the urinary space.
Here is the what happens in these
people.
For some reason,
the cell grow out under the 703
market thicken it and then lay down a new lamb.
It's usually a little thinner than the original lama dens.
A very similar morphology can occur in
graph rejection.
So by alone,
you really can't make the diagnosis of the current meris.
Some of these people are memoli instead of showing a
thickening of splitting the base membrane,
they will show show so called electron dense
deposits.
And one time this was separated out of the so called electron
dense deposit disease.
But doctor B in France,
I think most people now feel this is nothing more than just in the
spectrum of variant of memos and
this particular variant of memoli nephritis.
The electron deposit disease seems to be even
more likely to re occur almost 100%.
And the French experience than the other form of me,
the thing is this is so rare.
You'll probably never see it.
We've only seen one case I know of in any
disease.
Kidney in the four or five years,
I've been at Hall the Kidney Bobs.
I told you that the problem that comes up with trying to diagnose with chronic
arthritis in the graph is a confusion that you run into with the
same changes that apparently can occur with chronic
rejection without an underlying immm basis
immune complex or anti GB M process.
This is a kidney of a five year old
boy who had well documented dysplastic kidney
disease.
He had his original native kidneys removed at a very young age.
He had nothing to suggest any type of underlying
immunological problem over the next couple of
years,
he went into chronic vascular rejection at the time of
autopsy.
Those previous dark slides showed a tremendous
some sang thickening and widespread thickening
memories changed the basement membrane as well as widespread
split in the basement membrane.
But in contradistinction to me politic arthritis,
those were shrunken retracted,
they looked a trophic as well as showing these other changes I
talked about and minopoli the is
marked and large,
sometimes three and four times the diameter of a
normal.
And I think that's part of the best way to differentiate
between the memo type change you can get is a
chronic rejection phenomena from those
of the true recurrent memo plus the
correlation of clinical and I fluorescent data.
But this is this child at the time of death.
You can see he does have typical
widespread splitting of the basement membrane and he
also has circumferential mass and positioning
very similar to what we saw in that well documented
case of me,
he does not have deposits,
the ones with me commonly will have
deposits but they can be somewhat focal
and may,
you may miss them
another disease entity that Doctor mcfall doesn't
mention.
And we have not,
well,
we have had some recurring anti GB MS but they really
haven't expressed themselves moral to the patient.
Went ahead and lost his graph because of rejection.
But in early work of Dixon,
he did have at least one rapidly
progress.
Arthritis re occur within the first couple of days of transplantation due
to anti GB M arthritis.
And this is just an example of good pastures.
And the point I wanna make here,
this is not in a graph.
If you ever see this degree of crescent
formation in a graft,
you can be almost absolutely sure that that
patients got recurrence of arthritis.
Crescents are just not prominent and graft rejection
of any type either hyper acute,
acute or chronic.
You may see a few scattered small crescents,
but crescents of this size are just almost half of the mo
or occurring to mars in the ground.
And this is not again,
it's not a graph,
it's just a good,
good pastures.
But the original case of Dixon did reoccur with a
morphology identical to this
and this is a case of just how you
might work up a a problem of the
current arthritis.
This patient and his graft
in about six months or one year.
I'm not sure.
Now showed some degree of sang
proliferation masang thickening as you can see here
and all of these changes can occur as a part of a graph
rejection.
So how are you gonna try to separate them out?
Well,
one thing is to look around and see what are the vascular
changes using?
The cha changes in the due to rejection
always less severe than those in the vessels.
If you look in the vessels look pretty clean and yet
your is showing this degree of proliferation,
you really got to start thinking about Ken,
does this guy have recurrent glome arthritis
or at least part of this problem due to recurrent arthritis.
We did E M on this particular case
here.
This is a basement membrane.
Here you see these electron dense deposits.
This is his,
I mean this is his graph,
you can get varying degrees of deposits and the G
is a part of rejection to that again,
that makes the process difficult.
But our experience,
we just don't see this type of the type of immune
complex electron dense deposits very often and she
have been correlated with arthritis
if you go back and look at his original kidney.
This is one that I didn't,
I don't have pictures of it.
But until you go back and look at the original kidney,
you see he does have this is kind of a non specific sri
in this case.
But you know,
you look at his native kidney.
Doctor mcfall tells you he had on his native
kidney.
And then sometimes if you have ems on his native kidney,
you had deposit some of those in the graph that pretty much seals the
diagnosis.
Well,
in this case,
we didn't have E M but sometimes you can take the blocks out of
which we did here.
And we were able to demonstrate that in his native kidney
on paraffin embedded material,
we were able to demonstrate again,
electron dense deposits that have identical location
in the basement membrane to the deposits that he's
manifested in his graph
here is not quite as good.
This was paraffin embedded material.
I know that's not very good,
but considering it's coming from paraffin,
it's it's uh not bad and especially you can make out the
electron dens deposits right in trouble.
So in this case,
by doing a little detective work in correlation clinically and Doctor
mcfall is helping I help him with E M and
you could pretty well establish this guy did have some
degree of recurrent arts.
But I would predict that if this guy loses his graft,
he'll most likely lose it because of rejection,
not really because of the recurrent arthritis.
And we just talked about previously this morning,
the changes you see as part of graph rejection that can be
confused with current fires.
This is a typical change you see in
rejection.
And we've already talked about this memin change.
You can see as part of chronic graph rejection which should not be
mistaken for memin arthritis.
I think what I'm trying to point out is right here.
This is another biopsy an E M done on a
graph and a patient that had documented uh dysplastic
kidneys had no reason to have immune complex uh
anti GB M arthritis in his graph on
E E M.
Although his was negative,
he demonstrated some sub electron dense
deposits.
This is these type of closes that they
look different from a classic.
You seen a cut.
I really don't know what their significance is.
I think are very non specific,
but they are seen fairly commonly in graphs.
They were seen in 10 of 45 of the graphs in series in
which he did E M and they occur where the patient had native
fire or not.
So I would just warn you on articles that are published and
show a few deposits like that and try to push that
off as fires.
I think that may well be debris or it may,
it might actually be a manifestation of a de novo
uh arthritis related to uh
things not transplant fires or
histocompatibility change.
But there's just really no way of knowing at present
morphology of recurrent disease and
transplantation with James D
Mullin's Major US Air Force Medical Corps,
Wilford Hall US Air Force Medical Center,
Lackland Air Force Base
was produced through the mobile facilities of the television
division,
Academy of Health Sciences,
United States Army Fort Sam.
Houston,
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