- [Voiceover] So anemia of chronic disease is the second
most common cause of anemia in hospitalized patients
and it's a type of microcytic anemia,
microcytic anemia.
So, that tells us that anemia of chronic disease
is somehow due to a problem,
a problem in producing hemoglobin
because we know that all microcytic anemia's
result from a problem in producing hemoglobin.
The second thing that's really important about this disease
is that it's always, always, always, always related
to some inflammatory condition.
So that's to say that there must be some source
of inflammation in the body for this disease to result.
Now, anemia of chronic disease has absolutely everything
to do with the molecule, hepcidin
which is a polypeptide, is just a fancy term
for a chain of amino acids that's produced by the liver
that serves as the bodies major iron regulator.
And by regulator, I mean that when
the serum iron levels are low,
when the bodies iron levels are running low,
there's a low production of hepcidin.
But, when the bodies iron storage are running high
or when there is excessive amount of iron in the body,
the liver increases it's hepcidin production
and it does this because the hepcidin
then turns around and it decreases serum iron,
decreases serum iron.
And it does this, it decreases serum iron
in a couple of different ways.
And to understand how it decreases it,
I guess we'd have to go back for a couple seconds
to understand iron physiology.
So, we talked about how iron is absorbed it the duodenum,
but something we didn't mention is that
at the base of these cells in duodenum
is this channel called ferroportin
and ferroportin is what allows the iron
to go across these cells in the duodenum
and be absorbed into the bloodstream.
Now hepcidin comes in and it blocks
the ferroportin channels and by doing so,
it inhibits the absorption of the iron from the gut.
So, that's the first way in which hepcidin acts
to decrease serum iron levels.
Now, I'm going to scroll down,
scroll down just a little,
okay, so secondly, let's take a look at the liver,
and here's a blood vessel that has blood in it
and we know that blood has lots of red blood cells in it.
And every 120 days or so, each one of these red blood cells
is taken out of commision, it's retired
and it's degraded by cells in the liver called macrophages.
So, these red blood cells are broken down by
the macrophages and inside the red blood cells
we know we have lots of hemoglobin
and the hemoglobin has iron in its center,
and the iron that is released from the degradation
of the red blood cells isn't just thrown away,
instead it's saved and it's recycled
to be used later on to make new red blood cells.
So, what hepcidin does in this scenario
is it comes in and it inhibits the degradation,
it prevents a degradation of these red blood cells,
and it does so to prevent this iron
from being saved and being recycled later on.
So this is the second way in which hepcidin
acts to decrease serum iron.
So, moving to the side just a little,
so just to quickly summarize what hepcidin does
is it decreases serum iron by decreasing
the absorption of iron from the gut
and decreasing recycling by inhibiting
the degradation of red blood cells.
And, in normal people, hepcidin is released
in response to an increase in serum iron, right?
So it's essentially the bodies compensatory mechanism
to deal with too much iron.
Now, in the case of anemia of chronic disease,
hepcidin is released in response to
any inflammatory condition,
so any condition in which there's inflammation.
So firstly, what do I mean by inflammatory condition?
Well, I mean things such as infection,
because we know our body mounts an inflammatory response
to protect us from infections.
Now I also mean things like cancer,
who's malignancies a pretty inflammatory condition
and also autoimmune diseases, autoimmune diseases,
and usually what comes to mind with autoimmune diseases
is things like rheumatoid arthritis or lupus
but really any autoimmune condition
can do the same thing.
So these are just three of the most common causes
of inflammation but really there's several other disorders
that could lead to the same response.
Now, when there's any source of inflammation in the body,
the body releases cytokines
or small signalling molecules.
And these cytokines cause
an increase in hepcidin production.
The hepcidin then decreases the absorption and recycling
of iron to lead to a decrease in serum iron.
That much we've already established.
Now this decrease in serum iron
then leads to a decrease in hemoglobin production,
and that decrease in hemoglobin production
is what leads to the anemia.
And that's how an inflammatory condition
or a chronic disease leads to anemia.
Now, I guess something that we
haven't really addressed very well,
is why would you want there to be a decrease
in serum iron in response to an inflammatory condition,
why does this pathway even occur?
And the response to that is really important.
So, in conditions such as, for example,
such as infection, bacteria thrive off of iron.
They use it as an essential nutrient to grow.
So really what the body does is quite smart,
it essentially plays keep-away with the iron.
So it releases hepcidin to keep away the iron
so that the bacteria can't use it to grow.
And really, this same thing occurs
in cancer and in autoimmune condition
in which these cells use iron as an essential nutrient.
So that is essentially the background
and the pathophysiology of anemia of chronic disease.