00:01
Let’s walk through now the pathogenesis
of your anemia of chronic disease
and have you pay attention
to what’s in bold here –
the increase or
normal ferritin.
00:11
In other words, no decrease in ferritin.
00:12
Are we clear?
What’s your patient suffering from?
Oh, some type of chronic
disease including --
Maybe it’s a female that has
something like Hashimoto
or maybe there is rheumatoid arthritis,
maybe infection,
cancer, malignancies.
00:30
That’s the underlying issue.
00:32
Next, what happens?
Let me take you step by step.
00:35
Anemia of chronic disease, number one,
serum iron might be mildly decreased.
00:41
Number two, take a look
at the ferritin here.
00:44
And here, in the graph,
something that we have not
seen in any other graph
of iron study is this
little discussion.
00:53
See that arrow coming out of the
liver moving towards this hepcidin.
00:58
Well, that’s another substance that we have
not seen in any other iron study graph.
01:03
So this acute phase reactant that
is being released by the liver,
in response to this chronic
disease, which is inflammatory,
is specifically
known as hepcidin.
01:14
This you have to know.
01:17
This hepcidin, as you see here,
you see that green block?
That green block is blocking literally
the release of iron from your ferritin.
01:26
Where are we going with this?
Well, if you block or release or inhibitor
the release of iron from your ferritin,
guess what?
Tell me about your ferritin level.
01:38
It is abnormally either normal
or perhaps even increased.
01:44
In iron deficiency, did
you have such a hepcidin?
Of course not.
01:48
So therefore, whenever
you had iron deficiency,
serum iron was decreased, thus
ferritin was decreased, are we clear?
Here, however, the case,
definitely different.
01:59
We have hepcidin coming
in, blocking the release.
02:00
But this important.
02:03
So what is ferritin?
Well, for the most part, you think of
this as being a bone marrow macrophage.
02:07
Number two, where else would you
perhaps reabsorb some of that iron?
You should know this from the
discussion of hemochromatosis.
02:15
If it’s hereditary hemochromatosis, then
you know that there is unobstructed,
unopposed reabsorption of iron from
the intestine, intestine, intestine,
isn’t that the definition
of hemochromatosis?
Too much reabsorption of iron from the
intestine, putting it into your blood.
02:29
Correct?
That’s hemochromatosis.
02:32
What do you think normally
regulates the amount of iron
that is being reabsorbed
from the intestine?
Wow!
It’s hepcidin?
Yeah, it is.
02:41
So now, if you have too much
hepcidin, guess what it does?
It inhibits the release
of iron, period.
02:47
Either from ferritin, bone marrow
macrophage or number two, the intestine.
02:52
Is that clear?
So you might have a patient that has slightly
decreased levels of iron serum-wise.
03:00
Ferritin, however, will
be normal or increased.
03:02
Let’s go with your microcytic though.
03:03
So if it’s microcytic and you have
complete blockage of your ferritin,
you have an increase in ferritin,
what is my TIBC relationship here?
Inverse, isn’t it?
So you have an increase –
Increase or decrease?
Good. You have a decrease in
TIBC, inverse relationship.
03:21
And what is it that’s
saturating transferrin?
That’s that question that I
had post to you early on.
03:28
This is where it becomes
really important.
03:31
Good. It’s the ferritin.
03:32
So if the ferritin’s blocked,
how in the world can you possibly
saturate the transferrin?
You cannot.
03:39
So what’s my transferrin saturation?
Decreased.
03:42
Is that clear?
One more time.
03:43
What about serum iron?
Maybe mildly decreased.
03:47
Number two, increased
ferritin if it’s microcytic.
03:50
Number three, a
decrease in TIBC, good.
03:53
And number four, you have a decrease
in transferrin saturation.
03:57
This is for microcytic.
03:57
However, is it a possibility that
you might have normocytic ACD?
Absolutely.
04:04
And at that point, you’ll have
some of these interleukins,
which is then shutting
down my bone marrow,
resulting in non-hemolytic and
normocytic type of picture.
04:11
Do not forget that.
04:13
Not to worry.
04:15
I’ll repeat it when the
time is right as well.
04:17
Anemia of chronic disease.
04:19
We’ll take a look at iron accumulating
in your Prussian blue stain.
04:24
This is important for
you to understand this.
04:26
There is bone marrow macrophage
and there’s your ferritin, okay?
So we’re in the bone marrow, you’re
seeing large open spaces here.
04:32
And in your bone marrow,
what is it that allows for
iron to be then delivered
to your bone marrow?
That of course would
be transferrin.
04:40
So transferrin is going to then bring
the iron into your bone marrow, great.
04:43
Next, well, the iron is then
going to start accumulating
in your bone marrow macrophage.
04:48
We’ll go ahead and call
this the ferritin, clear?
At some point in time when ferritin
degrades, you call this hemosiderin.
04:56
Hemosiderin usually is not going
to kill you, not going to cause –
Usually doesn’t cause
massive tissue damage.
05:04
However, if it accumulates in abnormal
tissue, it may indicate the pathology.
05:09
For example, you’ve heard of
hemosiderin-laden macrophages in the lung.
05:11
Correct?
And that’s your heart failure cell.
05:15
It’s not that the hemosiderin is actually
fully causing damage to the tissue,
but my goodness gracious, it’s presence
in the lung parenchyma or interstitium,
definitely means that
pathology is occurring.
05:26
Is that clear?
Versus hemochromatosis, which is
also going to be increased iron,
but that increased iron will then actually
cause damage to organs such as the skin,
the bronze cause damage to the
pancreas, no insulin, diabetes.
05:43
Bronze, diabetes.
05:45
Let’s take a look at
some other factors here.
05:47
Ferritin synthesis.
05:47
Macrophages, hepatocytes
and cytochrome system is going
to help you with all of this.
05:55
So ferritin, bone marrow
or coming from your liver.
05:59
Next, usually, we have a
decrease in serum ferritin.
06:03
This is equivalent to a
decrease in iron stores
whereas if you have an
increase in serum ferritin,
this is equivalent to
increase in iron stores.
06:13
But the one big exception where
we saw an increase in ferritin
but still resulting in a type of anemia,
was once again, anemia of chronic disease.
06:20
This is a nice little discussion here
so that you can see when applying
your Prussian blue stain,
then what you’re only seeing
here staining is the iron.
06:32
Everything else that
you see here, well,
it’s not containing the
increased amount of iron here.
06:36
The only other thing that I wish
to bring your attention is that
if you did an H and E stain,
which they will give you, then this
iron is going to appear what color?
Brown.
06:47
So those of you that have gotten into
the habit of only seeing blue iron,
get away from that.
06:51
It only depends on the stain.
06:54
So if you’re suspecting
hemochromatosis on H and E,
you find it to be brown.
07:00
If it’s Prussian blue and
you’re ordering this,
then this will then
show you the blue.
07:04
I hope that’s clear.
07:06
A very important point.