00:01
Continuing our discussion
of multiple myeloma,
apart from serum
protein electrophoresis,
what are the features
that you expect to find?
Well, if you take a
look at the skull,
you find that you have
punched up lesions.
00:15
It's a monoclonal gammopathy,
you expect there to be IgG or IgA,
but that not IgM.
00:20
And these light chains.
00:22
Light chains are once again
into kappa lambda,
and majority of them will be kappa.
00:27
And as the picture would show you,
oftentimes,
actually almost on your boards,
they have to give you.
00:33
If they want you to
choose multiple myeloma,
they'll give you
lytic bone lesions,
and these are punched out lesions,
not wide areas of complete
destruction of the bone.
00:44
The reason I bring that
to your attention is
when I talk about
Langerhans cell histiocytosis
There'll be a sub tab called
eosinophilic granuloma test.
00:53
And that type is
where you will also find
destruction of the bone,
but it's quite chaotic.
00:58
It's not so chaotic,
in plasma cell multiple myeloma.
01:02
What I mean by that
is the punched out legion
almost looks as though
that the skull was shot by a bullet
going right through it.
01:12
Now, I have to be careful as to
how I use the word chaotic though
because it is going to
cause chaos in your body.
01:19
So once you start having
these lytic bone lesions.
01:23
The bone is very, very weak.
01:24
Your patient is not prone
to pathologic fractures.
01:27
In addition, the bone which is
the major reservoir for calcium.
01:34
The calcium is now being leaked
into circulation in great quantity.
01:37
You can expect your patient,
no doubt to have hypercalcemia.
01:41
That calcium is going to
pass through the glomerulus.
01:44
You can absolutely expect
your patient have hypercalciuria.
01:48
And with all this calcium
that's now in your urine,
who would you not expect
there to be calcium stones?
Everything is a story
Makes you understand
as to how the disease initiates
from the bone marrow.
02:02
Well, plasma cells, IgG and IGA
and how it wreaks havoc
on the bone, specifically.
02:09
A couple other things
in terms of symptoms.
02:11
I'm giving you the
fundamentals of multi-myeloma.
02:14
There'll be other things
such as Reuleaux formation,
but that is nonspecific.
02:18
And I'll give you a little
bit of detail about that.
02:21
And there could be issues with
the kidney of Bence-Jones protein.
02:24
But Bence-Jones protein
just means light chains.
02:27
You're gonna find
light chains and other diseases.
02:29
Lytic bone lesion, bone marrow,
plasma cell, multiple myeloma,
IgG, IGA, M spike, nonspecific.
02:37
Is that enough information?
Absolutely.
02:39
Get your question, right.
02:41
The picture that
you're seeing here,
upon histology would be
from the bone marrow.
02:46
A bone marrow aspirate
in which you would then find
tons of plasma cells.
02:50
How can you identify
these plasma cells?
Rows upon, rows of rough
endoplasmic reticulum,
and if it's multiple
myeloma, specifically
from the bone marrow,
and what kind of immunoglobulins
are these den producing please?
IgG or IGA?
With all this being produced,
then what wave is then
going to be affected?
Good. About M wave
and now you have created a M-spike.
03:19
Signs and symptoms
of multi-myeloma
Talk about that bone.
03:23
So here you might have
osteoclastic-activating factor.
03:26
Many times Interleukin-1or 6
might be involved
to remember that from immunology?
Interleukin 1 or 6,
all that osteoclastic activity
then causing bone infiltration.
03:38
That'd be chronic pain,
the bone is now weakened,
your patient is now susceptible
to pathologic fracture.
03:44
With all the bone being destroyed,
well, no doubt
that the patient is suffering
hypercalcemia, hypercalciuria,
and perhaps calcium stones.
03:54
Renal failure in these patients can
occur through one of two mechanisms.
03:58
The first is a result of a high
level of immunoglobulin light-chains
forming obstructing
intratubular cast.
04:04
This is called
myeloma cast nephropathy.
04:06
The other mechanism is through
amyloid deposition.
04:10
You're going to have
amyloid deposition.
04:13
And this amyloid then is
stained with your Congo Red,
which gives you what color?
Good.
04:20
Apple green birefringence.
04:23
In addition, you have these
Benjamin's proteins
but then you also have
Tamm-Horsfall casts.
04:30
And all of this is then going to
cause major damage to the tubules
eventually leading into
renal failure.
04:36
Amyloid deposition.
04:41
What's interesting about
plasma cell?
Neoplasms or multi-myeloma.
04:46
You would think,
you know, just by theory,
Dr. Raj you're producing
all these immunoglobulins
how is it possible that the patient
is susceptible to infection.
04:56
You completely lose
the proper proper protocol,
for isotypes switching
of immunoglobulin,
Remember you have to have IgM-1.
05:06
You have to have isotype switching
into the type of immunoglobulin
that's necessary
to fend off the
antigen or infection.
05:15
In plasma cell multi-myeloma,
my goodness,
you lose that isotype protocol.
05:21
So therefore,
even though you might be producing
all of these immunoglobulins,
it doesn't mean
that you're hyperimmune.
05:27
In fact, just the opposite.
05:30
Your immunity
is impaired or compromised,
your patient is susceptible
to infection.
05:35
You're producing the wrong.
05:36
You've lost the proper organization
of immunoglobulin.
05:44
Clinically, who's your patient?
Almost always older.
05:48
Now, unfortunately,
we don't have
proper methods of controlling
multi-myeloma, not yet.
05:54
Older the patient gets
more to multi-myeloma,
I can almost say
guaranteed death, unfortunately.
06:01
A very scary.
06:02
Incidence increases with age,
prognosis very poor.
Look at this.
06:07
three years
survival.