All right, welcome back.
We've talked about the biology of neoplasia.
We talked a bit about how cancers
interact with their host body.
Now we're going to talk about why
cancers cause illness and death,
so the morbidity and mortality of cancer.
we will break this down into kind of four different
areas, paraneoplastic syndromes are first up.
We'll talk about local growth and invasion.
We'll talk about metastases, and we'll
talk about the effects of therapy.
And all of these play in again to the morbidity
mortality that we see with malignancy.
First up is paraneoplastic syndromes.
And really what this means, technically is
next to the neoplasm, it's paraneoplastic.
But what it really means is that this syndrome,
or these syndromes, because they're multiple
are caused by or result from the
presence of the cancer in the body,
but not the actual physical presence of cancerous
tissue in the part of the organ affected.
So that means that there are
things being released by the tumor
into the circulation that are
causing effects at a distance.
And that's referred to as a paraneoplastic syndrome.
Circulating bioactive products.
There are several different
kinds of paraneoplastic processes
and it's also important to know that
they can come from both benign tumors,
tumors that are not considered malignant,
and don't have a lot of genetic instability,
but also for malignant tumors.
And I'll try to emphasize both as we go through this.
So there are four general paraneoplastic
processes that we're going to be talking about.
There's anemia, there's hypercalcemia,
hypercoagulability, and cachexia.
And we'll cover these each in turn.
Anemia is first up.
And anemia is actually multifactorial, and is a very
common paraneoplastic manifestation in malignancy.
So a variety of things can cause inflammation.
As you see on the ends, infection and immunotherapy
but cancer is what we're talking
about here causing inflammation.
That inflammation systemically will release
Interleukin-6, IL-6 that acts on the liver.
The liver is responding to IL-6
thinking, 'Gee, we're under attack,
we need to do certain things that prepare
the body for a microbial onslaught.'
One of the major proteins that is going to
affect the hematocrit levels of erythrocytes
is going to be hepcidin, small molecular
weight peptide synthesized by liver,
whose role is to regulate iron levels systemically.
And when the liver sees
Interleukin-6, it cranks out hepcidin,
which decreases iron absorption from the
GI tract and increases iron sequestration.
Why is this happening?
Well, it turns out that we are trying to
prevent microbes from getting a head start.
If we make iron limiting, we can actually
usually get a leg up on on the microbes.
So that's kind of the physiologic evolutionary
purpose of this particular pathway.
But if cancer elicits inflammation,
making IL-6, now I've sequestered iron,
and I can't use it for making erythroid
elements so it's iron restricted erythropoiesis.
That inflammation is also making tumor necrosis
factor, Interleukin-1, and interferon gamma.
Those things will actually act to diminish
the erythropoietin response to anemia.
So whenever we're anemic, we crank out
more erythropoietin from our kidneys.
But those particular inflammatory cytokines
turn down the synthesis of red blood cells
in response to erythropoetin and so we have
kind of cut off that particular arm too.
So nutritional deficiencies, the
effects of chemotherapy and radiotherapy
and marrow infiltration by a tumor will mean that
the marrow cannot respond appropriately to EPO,
even if all the other levels are appropriate.
Iron restricted erythropoiesis clearly also
diminishes the marrow response to erythropoietin.
And there's more.
Renal insufficiency, if due to chemotherapy
or due to other kind of comorbidities
will result in less erythropoietin
production, so therefore, more anemia.
And finally, we're going to be having,
because of the effects of tumor,
we may have bleeding due to leaky blood vessels.
We may have hemolysis, rupture of red blood cells
due to activation of the coagulation cascade,
and there'll be diminished red cells survival.
All of these come together and result in anemia.
So you can see that that because all the
multiple boxes that we have on the screen here,
that cancer can be a very common
cause of low red cell count.