5.2b Microcytic Anemias

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S… Speaker 1 (5.2b Microcytic Anemias)

The next of the microcytic anemias is anemia of chronic disease.

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S… Speaker 1 (5.2b Microcytic Anemias)

Now,

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what is anemia of chronic disease?

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This is anemia that's associated usually with chronic inflammation or

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cancer.

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It's the most common type of anemia in hospitalized patients,

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and the idea here is that if there is a chronic disease that

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results in chronic inflammation,

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then there would be an increase in acute phase reactants.

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S… Speaker 1 (5.2b Microcytic Anemias)

One of those acute phase reactants is called hepcidin.

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And hepcidin,

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what it does is it sequesters iron within storage sites so that

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it cannot be used.

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S… Speaker 1 (5.2b Microcytic Anemias)

So hepcidin has the ability to lock iron into

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its storage sites,

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prohibiting iron from being transferred to other cells.

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So this limits the transfer of iron from the macrophages to the

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erythroid precursors.

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And if the erythroid precursors don't have access to iron,

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they're gonna have difficulty producing heme.

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And again,

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if heme is low,

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then hemoglobin will be low,

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and if hemoglobin is low,

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that's gonna result in a microcytic anemia.

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S… Speaker 1 (5.2b Microcytic Anemias)

So that's one consequence of hepcidin.

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The second consequence of hepcidin is that it can suppress erythropoietin

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production as well.

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And again,

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S… Speaker 1 (5.2b Microcytic Anemias)

if you suppress erythropoietin production,

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that's going to decrease the drive on the bone marrow to actually

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produce more cells.

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Now,

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one of the things to remember concerning this sort of sequence

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of events is that it actually makes sense what's going on.

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Iron is an essential

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nutrient for bacteria they require iron for their survival and

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so when there's chronic inflammation

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the body doesn't know that there's some sort of chronic disease like an autoimmune disease

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or that there's a cancer with a little bit of chronic inflammation associated with it.

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Instead, the body thinks that there is actually chronic inflammation because there

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is some sort of microbe present.

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And so what the body does is it releases hepcidin to hide away

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the iron so that the iron is not available for the bacteria.

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And that,

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you know, theoretically would then result in lack of the ability of

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the bacteria.

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to divide and to thrive.

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But obviously,

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in chronic disease,

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there is no infection.

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However,

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the effects of hepcidin are still felt.

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S… Speaker 1 (5.2b Microcytic Anemias)

And so this is called anemia of chronic disease.

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Now here I remind you that there's a decreased availability of

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iron.

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It's the same story as I've mentioned before.

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Decreased iron,

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decreased heme.

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Decreased heme,

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decreased hemoglobin.

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Decreased hemoglobin is gonna result in a microcytic

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anemia.

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Now, what are the lab findings going to be?

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Well,

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the lab findings are going to be based on our understanding of

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what is driving this disease process.

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So, for example,

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first of all,

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you're well aware of the fact that in anemia of chronic disease,

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there is going to be an inability to use storage

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iron.

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So, if the storage iron cannot be used,

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it's going to pile up,

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and as it piles up,

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there will be high stores of iron,

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and so the ferritin will be high.

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because the stores of iron are high.

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And at the same time,

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anytime the ferritin is high,

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the total iron binding capacity will go down.

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And that's because the number of transferrin molecules floating around in the blood will

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go down.

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And this is sort of the relationship that we've already explained in

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iron deficiency anemia.

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Another important feature or finding will be that the serum

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iron will be used.

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If the bone marrow cannot use the iron

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in the macrophages,

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it will begin to take the iron from the serum.

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And when it takes the iron from the serum,

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the serum iron will go down,

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S… Speaker 1 (5.2b Microcytic Anemias)

and at the same time,

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percent saturation...

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will also go down.

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So the serum iron will go down and the percent saturation

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will go down.

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And then finally,

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there'll be an increase in free erythrocyte protoporphyrin.

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S… Speaker 1 (5.2b Microcytic Anemias)

Again, that makes sense because you understand,

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S… Speaker 1 (5.2b Microcytic Anemias)

now that we have studied a little bit of the biochemistry here,

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that heme is made

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of iron plus protoporphyrin

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And the problem here is the accessibility of iron.

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However,

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there is no problem with protoporphyrin,

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and therefore,

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protoporphyrin will be produced,

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and some of it will be floating free in the red blood cell.

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S… Speaker 1 (5.2b Microcytic Anemias)

It will not be attached to iron.

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S… Speaker 1 (5.2b Microcytic Anemias)

And so there'll be an increase in free erythrocyte protoporphyrin.

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S… Speaker 1 (5.2b Microcytic Anemias)

Now let me just clarify one bit of confusion that can

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arise depending on which textbook you're reading,

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S… Speaker 1 (5.2b Microcytic Anemias)

and that is that when you consider this sequence of events,

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it's very similar to the sequence of events that would occur with iron deficiency

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anemia.

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Remember that in iron deficiency anemia,

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S… Speaker 1 (5.2b Microcytic Anemias)

the first phase was to have a normalcytic anemia,

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and then eventually as the iron deficiency becomes worse,

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S… Speaker 1 (5.2b Microcytic Anemias)

the patient then gets a microcytic hypochromic anemia.

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S… Speaker 1 (5.2b Microcytic Anemias)

Well, the exact same thing happens in anemia of chronic disease.

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So,

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otherwise stated,

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S… Speaker 1 (5.2b Microcytic Anemias)

what I'm trying to say is that in the early phase of anemia of chronic disease,

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S… Speaker 1 (5.2b Microcytic Anemias)

the patient first develops a normal scytic anemia.

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And then as the anemia of chronic disease becomes severe,

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S… Speaker 1 (5.2b Microcytic Anemias)

and I should say in particular as the iron deficiency becomes more severe,

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the patient can then go on to develop a microcytic

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anemia.

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And the reason I'm highlighting this point here is because if you look in textbooks,

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S… Speaker 1 (5.2b Microcytic Anemias)

some textbooks put anemia of chronic disease as a microcytic anemia.

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and other textbooks classify it as a normalcytic anemia,

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S… Speaker 1 (5.2b Microcytic Anemias)

and it can actually do both,

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and so I just want you to understand that sequence of events that we've already covered

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when we talked about iron deficiency anemia.

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Now, what is the treatment of anemia of

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chronic disease?

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The treatment would be to address the underlying cause.

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So if there's a chronic inflammatory state,

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for example,

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the patient has an autoimmune disease,

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then we'd want to address the autoimmune disease by decreasing the inflammation

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S… Speaker 1 (5.2b Microcytic Anemias)

will decrease the production of hepcidin.

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S… Speaker 1 (5.2b Microcytic Anemias)

And by decreasing hepcidin,

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S… Speaker 1 (5.2b Microcytic Anemias)

we'll then be able to free the iron that's present in

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S… Speaker 1 (5.2b Microcytic Anemias)

the storage sites and make it available to the bone marrow.

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Another important treatment could be erythropoietin.

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S… Speaker 1 (5.2b Microcytic Anemias)

Remember that in a subset of,

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remember that one of the effects of hepcidin is to actually decrease the

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production of erythropoietin.

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And giving exogenous erythropoietin is particularly useful in a subset

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of patients, especially in cancer patients.

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So that if patients have cancer and anemia of chronic disease associated with

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that, erythropoietin can be particularly helpful in those patients.

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S… Speaker 1 (5.2b Microcytic Anemias)

The next of the microcytic anemias that I would like to discuss is called

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sideroblastic anemia.

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Now sideroblastic anemia is going to be due to a defect in

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protoporphyrin synthesis.

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Again,

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S… Speaker 1 (5.2b Microcytic Anemias)

go back and remind yourselves that heme,

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as I've stated many times already,

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heme is composed of iron plus

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protoporphyrin.

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And if there is a disorder in the ability

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S… Speaker 1 (5.2b Microcytic Anemias)

to produce protoporphyrin,

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then low protoporphyrin would result in low heme,

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and low heme would result in low hemoglobin,

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and low hemoglobin would then result in a microcytic anemia.

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So that's the paradigm that we've established,

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and of course this follows that.

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So let's read what we have here.

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Sideroblastic anemia is due to defective protoporphyrin synthesis.

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And again,

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that deep...

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that decrease protoporphyrin will eventually lead to a microcytic anemia now

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in order to understand

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sideroblastic anemia,

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you then need to understand the biochemistry of protoporphyrin,

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and here's where things get a little bit complex.

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Recall that protoporphyrin is actually synthesized by about seven

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or eight chemical reactions,

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so there are a series of reactions that are important for the synthesis of

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protoporphyrin,

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and recall that some of these reactions occur within the cytoplasm

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of the cell, and some of these reactions occur within the mitochondria of the cell,

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and of course, these reactions are occurring in the

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the progenitor cells of the red blood cells in the erythroblast.

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I don't want to go through every one of these reactions because

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that would get unnecessarily complex for the discussion that

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we want to have,

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but there are some very high yield reactions within this

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sequence that you do need to be familiar with,

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and they are highly tested on examinations,

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and of course,

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they're clinically relevant because they apply to our discussion

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of sideroblastic anemia.

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S… Speaker 1 (5.2b Microcytic Anemias)

Let me go back and create a little bit of a whiteboard here and remind you that

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the very first step in the production of protoporphyrin is that succinyl

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-CoA,

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which I'm going to just abbreviate here as this,

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is converted into amino -lavalunic acid.

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That's the first step.

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And this particular reaction is catalyzed by an enzyme called

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amino -lavalunic acid synthase,

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also called ALAS,

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A -L -A -S.

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Important to note that ALAS is the rate -limiting step in

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the production of protoporphyrin.

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So that is important to know.

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And the second important point is that vitamin B6 is

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a cofactor for this enzyme.

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So these are two important things to be aware of.

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The next step is going to be that ALA is

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going to be converted to porphylbolinogen.

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So I'm just going to call it porphylb.

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P -O -R -P -H -O -B,

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porphoblinogen.

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And the important enzyme that catalyzes this reaction is called ALAD,

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A -L -A -D,

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dehydrogenase.

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So ALAD.

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These are the first two reactions within this sequence.

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Now, the next series of reactions are,

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you know,

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there's a series of reactions that occur,

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so there's a few more reactions,

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and then you get to the very final reaction.

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And in the final reaction,

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you know, eventually you're

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going to generate from here you're going to generate protoporphyrin and protoporphyrin

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and in the final reaction protoporphyrin is bound to iron all

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right and protoporphyrin and iron are going to yield heme so that

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we are aware of the joining of protoporphyrin to iron occurs

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by an enzyme called ferrokelatase

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Ferrokelatase, F -E -R -R -O.

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Ferrokelatase is what catalyzes this reaction,

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number one.

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Number two,

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this reaction occurs within the mitochondria.

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So that's important to know,

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S… Speaker 1 (5.2b Microcytic Anemias)

and you'll see why in a moment.

10:37

S… Speaker 1 (5.2b Microcytic Anemias)

Let's go back to our slides,

10:38

S… Speaker 1 (5.2b Microcytic Anemias)

and hopefully this now becomes clear.

10:41

S… Speaker 1 (5.2b Microcytic Anemias)

Protoporphyrin is synthesized in a series of reactions.

10:45

S… Speaker 1 (5.2b Microcytic Anemias)

And important is that the final reaction attaches protoporphyrin

10:50

S… Speaker 1 (5.2b Microcytic Anemias)

to iron to make heme.

10:52

S… Speaker 1 (5.2b Microcytic Anemias)

And what's the name of the enzyme again?

10:54

S… Speaker 1 (5.2b Microcytic Anemias)

Ferrokelatase.

10:55

S… Speaker 1 (5.2b Microcytic Anemias)

And where does that occur?

10:57

S… Speaker 1 (5.2b Microcytic Anemias)

In the mitochondria.

10:59

S… Speaker 1 (5.2b Microcytic Anemias)

At the same time,

11:01

S… Speaker 1 (5.2b Microcytic Anemias)

while protoporphyrin is being generated by this series of reactions,

11:05

S… Speaker 1 (5.2b Microcytic Anemias)

iron is being transferred to the erythroid precursor.

11:08

S… Speaker 1 (5.2b Microcytic Anemias)

So here's the idea.

11:10

S… Speaker 1 (5.2b Microcytic Anemias)

You know, you've got this erythroblast,

11:12

S… Speaker 1 (5.2b Microcytic Anemias)

okay? And here's the nucleus of the erythroblast.

11:15

S… Speaker 1 (5.2b Microcytic Anemias)

And adjacent to the nucleus is usually where the mitochondria sit.

11:19

S… Speaker 1 (5.2b Microcytic Anemias)

And so what's happening in the mitochondria or in the erythroblast is that...

11:23

S… Speaker 1 (5.2b Microcytic Anemias)

Protoporphyrin is being prepared,

11:25

S… Speaker 1 (5.2b Microcytic Anemias)

and eventually protoporphyrin's final reaction that generates protoporphyrin

11:29

S… Speaker 1 (5.2b Microcytic Anemias)

occurs within the mitochondria here.

11:31

S… Speaker 1 (5.2b Microcytic Anemias)

So protoporphyrin is produced in the mitochondria.

11:34

S… Speaker 1 (5.2b Microcytic Anemias)

At the same time,

11:35

S… Speaker 1 (5.2b Microcytic Anemias)

iron comes from the bone marrow macrophages,

11:38

S… Speaker 1 (5.2b Microcytic Anemias)

is transferred to the erythroblast,

11:41

S… Speaker 1 (5.2b Microcytic Anemias)

the cell that's producing the red blood cells,

11:44

S… Speaker 1 (5.2b Microcytic Anemias)

and then iron also gets transferred to the mitochondria.

11:48

S… Speaker 1 (5.2b Microcytic Anemias)

And when iron and protoporphyrin meet in the mitochondria,

11:51

S… Speaker 1 (5.2b Microcytic Anemias)

Iron then gets bound to protoporphyrin,

11:53

S… Speaker 1 (5.2b Microcytic Anemias)

and that's what creates heme.

11:55

S… Speaker 1 (5.2b Microcytic Anemias)

And so that's what I'm saying here,

11:57

S… Speaker 1 (5.2b Microcytic Anemias)

is that iron is transferred to the erythroid precursor.

11:59

S… Speaker 1 (5.2b Microcytic Anemias)

It enters the mitochondria to form heme.

12:03

S… Speaker 1 (5.2b Microcytic Anemias)

Now let's pretend for a minute that protoporphyrin is deficient,

12:06

S… Speaker 1 (5.2b Microcytic Anemias)

so that we're not making protoporphyrin.

12:08

S… Speaker 1 (5.2b Microcytic Anemias)

If we're not making appropriate protoporphyrin,

12:11

S… Speaker 1 (5.2b Microcytic Anemias)

iron will enter into the mitochondria and will be trapped there.

12:15

S… Speaker 1 (5.2b Microcytic Anemias)

It has no way of getting out.

12:16

S… Speaker 1 (5.2b Microcytic Anemias)

And when iron gets trapped within the mitochondria,

12:18

S… Speaker 1 (5.2b Microcytic Anemias)

it's going to pile up,

12:20

S… Speaker 1 (5.2b Microcytic Anemias)

because iron is going to continue to come in,

12:22

S… Speaker 1 (5.2b Microcytic Anemias)

so more iron and more iron and more iron will come into the mitochondria,

12:26

S… Speaker 1 (5.2b Microcytic Anemias)

and mitochondria are generally present.

12:28

S… Speaker 1 (5.2b Microcytic Anemias)

all around the nucleus,

12:29

S… Speaker 1 (5.2b Microcytic Anemias)

so these are gonna be mitochondria,

12:31

S… Speaker 1 (5.2b Microcytic Anemias)

and each of them is going to become loaded with iron.

12:34

S… Speaker 1 (5.2b Microcytic Anemias)

And as they become loaded with iron,

12:37

S… Speaker 1 (5.2b Microcytic Anemias)

that's going to create a ring of iron -loaded

12:41

S… Speaker 1 (5.2b Microcytic Anemias)

mitochondria around the nucleus of the cell.

12:44

S… Speaker 1 (5.2b Microcytic Anemias)

And that creates the classic cell that's seen within

12:48

S… Speaker 1 (5.2b Microcytic Anemias)

sideroblastic anemia,

12:49

S… Speaker 1 (5.2b Microcytic Anemias)

which is called a ringed sideroblast.

12:52

S… Speaker 1 (5.2b Microcytic Anemias)

And so that's what I'm saying here in this particular slide.

12:55

S… Speaker 1 (5.2b Microcytic Anemias)

Note what I say.

12:56

S… Speaker 1 (5.2b Microcytic Anemias)

Iron -laden mitochondria form a ring around the nucleus of erythroid

13:00

S… Speaker 1 (5.2b Microcytic Anemias)

precursors,

13:01

S… Speaker 1 (5.2b Microcytic Anemias)

and these are called ringed sideroblasts.

13:03

S… Speaker 1 (5.2b Microcytic Anemias)

So here's a classic image.

13:05

S… Speaker 1 (5.2b Microcytic Anemias)

This is a bone marrow biopsy.

13:07

S… Speaker 1 (5.2b Microcytic Anemias)

Of course, we would see this in the bone marrow.

13:08

S… Speaker 1 (5.2b Microcytic Anemias)

This is where the cells are being produced,

13:10

S… Speaker 1 (5.2b Microcytic Anemias)

and we can clearly see,

13:12

S… Speaker 1 (5.2b Microcytic Anemias)

see this blue color here?

13:13

S… Speaker 1 (5.2b Microcytic Anemias)

This represents iron.

13:14

S… Speaker 1 (5.2b Microcytic Anemias)

This is a special stain called a Prussian blue stain,

13:17

S… Speaker 1 (5.2b Microcytic Anemias)

and the Prussian blue stain is what marks iron.

13:20

S… Speaker 1 (5.2b Microcytic Anemias)

Now clearly, in this particular case,

13:22

S… Speaker 1 (5.2b Microcytic Anemias)

we see that there is iron that's accumulating in a ring around this

13:26

S… Speaker 1 (5.2b Microcytic Anemias)

cell.

13:26

S… Speaker 1 (5.2b Microcytic Anemias)

I'm going to clear this for you so that you can see it.

13:29

S… Speaker 1 (5.2b Microcytic Anemias)

Iron is accumulating in a ring around the nucleus of this particular

13:33

S… Speaker 1 (5.2b Microcytic Anemias)

cell.

13:34

S… Speaker 1 (5.2b Microcytic Anemias)

That's called a ring sideroblast.

13:36

S… Speaker 1 (5.2b Microcytic Anemias)

Here's another example of a ring sideroblast,

13:38

S… Speaker 1 (5.2b Microcytic Anemias)

and it indicates a sideroblastic anemia.

13:43

S… Speaker 1 (5.2b Microcytic Anemias)

One of the classic questions that examiners like to ask,

13:45

S… Speaker 1 (5.2b Microcytic Anemias)

they like to show you this picture,

13:47

S… Speaker 1 (5.2b Microcytic Anemias)

and they like to ask you,

13:48

S… Speaker 1 (5.2b Microcytic Anemias)

where is the iron located?

13:51

S… Speaker 1 (5.2b Microcytic Anemias)

I just gave away the answer.

13:53

S… Speaker 1 (5.2b Microcytic Anemias)

The answer is that the iron is present in mitochondria.

13:57

S… Speaker 1 (5.2b Microcytic Anemias)

That's high yield to be aware of.

13:59

S… Speaker 1 (5.2b Microcytic Anemias)

The iron is present within mitochondria.

14:02

S… Speaker 1 (5.2b Microcytic Anemias)

Siteroblastic anemia can actually be divided into congenital or

14:06

S… Speaker 1 (5.2b Microcytic Anemias)

acquired.

14:07

S… Speaker 1 (5.2b Microcytic Anemias)

It is important to know that the most common form of

14:11

S… Speaker 1 (5.2b Microcytic Anemias)

congenital siteroblastic anemia is due to a defect in ALAS.

14:16

S… Speaker 1 (5.2b Microcytic Anemias)

Remember that ALAS is the rate -limiting step.

14:19

S… Speaker 1 (5.2b Microcytic Anemias)

It is the step that catalyzes succinyl -CoA to

14:23

S… Speaker 1 (5.2b Microcytic Anemias)

become amino -lavalunic acid.

14:25

S… Speaker 1 (5.2b Microcytic Anemias)

And that is the key rate -limiting step,

14:29

S… Speaker 1 (5.2b Microcytic Anemias)

and a congenital defect

14:30

S… Speaker 1 (5.2b Microcytic Anemias)

of this enzyme is the most common cause of congenital sideroblastic

14:34

S… Speaker 1 (5.2b Microcytic Anemias)

anemia.

14:35

S… Speaker 1 (5.2b Microcytic Anemias)

Again,

14:36

S… Speaker 1 (5.2b Microcytic Anemias)

important to be aware of for the purposes of examinations.

14:40

S… Speaker 1 (5.2b Microcytic Anemias)

As far as acquired sideroblastic anemia is concerned,

14:44

S… Speaker 1 (5.2b Microcytic Anemias)

these are also very high yield.

14:46

S… Speaker 1 (5.2b Microcytic Anemias)

What are the common causes of acquired sideroblastic anemia?

14:50

S… Speaker 1 (5.2b Microcytic Anemias)

So one important cause of acquired sideroblastic anemia is alcoholism.

14:55

S… Speaker 1 (5.2b Microcytic Anemias)

Alcohol is a mitochondrial poison.

14:57

S… Speaker 1 (5.2b Microcytic Anemias)

It damages the production of protoporphyrin,

15:01

S… Speaker 1 (5.2b Microcytic Anemias)

and therefore it can lead to a sideroblastic anemia.

15:03

S… Speaker 1 (5.2b Microcytic Anemias)

Another important cause of sideroblastic anemia is lead poisoning.

15:07

S… Speaker 1 (5.2b Microcytic Anemias)

Lead has the ability to denature enzymes,

15:10

S… Speaker 1 (5.2b Microcytic Anemias)

and two of the enzymes that lead can denature are ALAD and

15:16

S… Speaker 1 (5.2b Microcytic Anemias)

ferroquilatase.

15:19

S… Speaker 2 (5.2b Microcytic Anemias)

All right,

15:19

S… Speaker 1 (5.2b Microcytic Anemias)

so a couple things.

15:20

S… Speaker 1 (5.2b Microcytic Anemias)

Number one,

15:21

S… Speaker 1 (5.2b Microcytic Anemias)

if a LAD is denatured,

15:23

S… Speaker 1 (5.2b Microcytic Anemias)

remember that a LAD was the second reaction in the production of protoporphyrin.

15:27

S… Speaker 1 (5.2b Microcytic Anemias)

If a LAD is denatured,

15:29

S… Speaker 1 (5.2b Microcytic Anemias)

that would then decrease our ability to produce protoporphyrin,

15:33

S… Speaker 1 (5.2b Microcytic Anemias)

and if protoporphyrin's not available,

15:34

S… Speaker 1 (5.2b Microcytic Anemias)

iron will become trapped in the mitochondria.

15:37

S… Speaker 1 (5.2b Microcytic Anemias)

And similarly,

15:38

S… Speaker 1 (5.2b Microcytic Anemias)

if ferroquilatase is not available,

15:40

S… Speaker 1 (5.2b Microcytic Anemias)

ferroquilatase is the name of the enzyme that links protoporphyrin with

15:44

S… Speaker 1 (5.2b Microcytic Anemias)

iron.

15:44

S… Speaker 1 (5.2b Microcytic Anemias)

And so if...

15:45

S… Speaker 1 (5.2b Microcytic Anemias)

iron can't get linked to protoporphyrin to make heme to eventually become hemoglobin

15:49

S… Speaker 1 (5.2b Microcytic Anemias)

to then leave the cell,

15:51

S… Speaker 1 (5.2b Microcytic Anemias)

iron will get trapped in the mitochondria as well.

15:53

S… Speaker 1 (5.2b Microcytic Anemias)

And so lead poisoning is another cause of a sideroblastic anemia.

15:58

S… Speaker 1 (5.2b Microcytic Anemias)

And the third acquired cause of sideroblastic anemia is vitamin B6

16:02

S… Speaker 1 (5.2b Microcytic Anemias)

deficiency.

16:02

S… Speaker 1 (5.2b Microcytic Anemias)

Now remember that the rate -limiting enzyme in this

16:06

S… Speaker 1 (5.2b Microcytic Anemias)

biochemical pathway was called ALAS,

16:09

S… Speaker 1 (5.2b Microcytic Anemias)

A -L -A -S.

16:12

S… Speaker 1 (5.2b Microcytic Anemias)

ALAS requires vitamin B6 as a cofactor,

16:15

S… Speaker 1 (5.2b Microcytic Anemias)

and so if there is a deficiency of vitamin B6,

16:18

S… Speaker 1 (5.2b Microcytic Anemias)

the ALAS enzyme will not function properly.

16:21

S… Speaker 1 (5.2b Microcytic Anemias)

That's the rate -limiting step for the production of protoporphyrin,

16:25

S… Speaker 3 (5.2b Microcytic Anemias)

and therefore...

16:27

S… Speaker 1 (5.2b Microcytic Anemias)

the patients will get a sideroblastic anemia.

16:30

S… Speaker 1 (5.2b Microcytic Anemias)

Now,

16:31

S… Speaker 1 (5.2b Microcytic Anemias)

what's the common circumstance in which patients get vitamin B6

16:35

S… Speaker 1 (5.2b Microcytic Anemias)

deficiency?

16:36

S… Speaker 1 (5.2b Microcytic Anemias)

Well,

16:37

S… Speaker 1 (5.2b Microcytic Anemias)

the important common circumstance would be isoniazid treatment,

16:40

S… Speaker 1 (5.2b Microcytic Anemias)

and that's a little pharmacology tie -in,

16:42

S… Speaker 1 (5.2b Microcytic Anemias)

so that patients who are on isoniazid therapy,

16:46

S… Speaker 1 (5.2b Microcytic Anemias)

they can become vitamin B6 deficient and can develop,

16:49

S… Speaker 1 (5.2b Microcytic Anemias)

as a consequence,

16:50

S… Speaker 1 (5.2b Microcytic Anemias)

a sideroblastic anemia.

16:52

S… Speaker 1 (5.2b Microcytic Anemias)

Now, what are the laboratory findings going to be in a sideroblastic anemia?

16:57

S… Speaker 1 (5.2b Microcytic Anemias)

Well,

16:57

S… Speaker 1 (5.2b Microcytic Anemias)

generally speaking,

16:58

S… Speaker 1 (5.2b Microcytic Anemias)

the way I summarize the laboratory findings is that the patients,

17:02

S… Speaker 1 (5.2b Microcytic Anemias)

they get a iron overloaded state.

17:04

S… Speaker 1 (5.2b Microcytic Anemias)

The idea here is that pretend for a moment that this is

17:09

S… Speaker 1 (5.2b Microcytic Anemias)

the erythroblast.

17:10

S… Speaker 1 (5.2b Microcytic Anemias)

This is the erythroid progenitor cell.

17:13

S… Speaker 1 (5.2b Microcytic Anemias)

It's the cell that's making red blood cells.

17:15

S… Speaker 1 (5.2b Microcytic Anemias)

So what's happening is that iron is coming into the cell.

17:18

S… Speaker 1 (5.2b Microcytic Anemias)

Here's the nucleus.

17:19

S… Speaker 1 (5.2b Microcytic Anemias)

and iron begins to build up in the mitochondria,

17:22

S… Speaker 1 (5.2b Microcytic Anemias)

and of course more iron,

17:24

S… Speaker 1 (5.2b Microcytic Anemias)

more iron comes in,

17:25

S… Speaker 1 (5.2b Microcytic Anemias)

until finally there's just a ton of iron in this cell.

17:28

S… Speaker 1 (5.2b Microcytic Anemias)

So the cell is getting loaded and loaded and loaded with

17:32

S… Speaker 1 (5.2b Microcytic Anemias)

iron, until eventually iron,

17:34

S… Speaker 1 (5.2b Microcytic Anemias)

because it has the ability to create free radicals,

17:37

S… Speaker 1 (5.2b Microcytic Anemias)

eventually iron will cause the cell to get damaged and die.

17:41

S… Speaker 1 (5.2b Microcytic Anemias)

And so when the free radicals are generated by all of this

17:45

S… Speaker 1 (5.2b Microcytic Anemias)

excess iron,

17:45

S… Speaker 1 (5.2b Microcytic Anemias)

this cell will die.

17:47

S… Speaker 1 (5.2b Microcytic Anemias)

when this cell dies a couple things are going to happen but most

17:51

S… Speaker 1 (5.2b Microcytic Anemias)

importantly the iron is going to leak out and when the iron leaks out

17:55

S… Speaker 1 (5.2b Microcytic Anemias)

The bone marrow macrophages will eat that iron,

17:58

S… Speaker 1 (5.2b Microcytic Anemias)

so there'll be high stores of iron in the bone marrow macrophages,

18:02

S… Speaker 1 (5.2b Microcytic Anemias)

and some of that iron could leak out into the blood,

18:05

S… Speaker 1 (5.2b Microcytic Anemias)

then causing an increase in serum iron.

18:08

S… Speaker 1 (5.2b Microcytic Anemias)

And so that's the way I sort of think about it,

18:10

S… Speaker 1 (5.2b Microcytic Anemias)

and that's how the labs sort of play out.

18:12

S… Speaker 1 (5.2b Microcytic Anemias)

These patients have a high ferritin because the bone marrow macrophages

18:16

S… Speaker 1 (5.2b Microcytic Anemias)

are going to eat all of that stored iron,

18:18

S… Speaker 1 (5.2b Microcytic Anemias)

are going to store all of that iron that comes off from the dead erythroid

18:23

S… Speaker 1 (5.2b Microcytic Anemias)

precursors.

18:24

S… Speaker 1 (5.2b Microcytic Anemias)

and because the ferritin is high,

18:25

S… Speaker 1 (5.2b Microcytic Anemias)

the TIBC obviously would be low.

18:27

S… Speaker 1 (5.2b Microcytic Anemias)

And then at the same time,

18:29

S… Speaker 1 (5.2b Microcytic Anemias)

the serum iron is going to be high,

18:31

S… Speaker 1 (5.2b Microcytic Anemias)

and because the serum iron is high,

18:32

S… Speaker 1 (5.2b Microcytic Anemias)

the percent saturation would also be high.

18:35

S… Speaker 1 (5.2b Microcytic Anemias)

And so I've already explained this,

18:37

S… Speaker 1 (5.2b Microcytic Anemias)

and I think this makes sense,

18:38

S… Speaker 1 (5.2b Microcytic Anemias)

but basically the key summary sort of phrase would be iron overloaded

18:43

S… Speaker 1 (5.2b Microcytic Anemias)

state. And by the way,

18:44

S… Speaker 1 (5.2b Microcytic Anemias)

if you're curious,

18:45

S… Speaker 1 (5.2b Microcytic Anemias)

when patients have hemochromatosis,

18:47

S… Speaker 1 (5.2b Microcytic Anemias)

which is also a disease in which they have an iron overloaded state,

18:51

S… Speaker 1 (5.2b Microcytic Anemias)

they have very similar laboratory findings.

18:53

S… Speaker 1 (5.2b Microcytic Anemias)

So hemochromatosis and sideroblastic anemia share the same

18:57

S… Speaker 1 (5.2b Microcytic Anemias)

laboratory findings as far as iron state or

19:01

S… Speaker 1 (5.2b Microcytic Anemias)

status is concerned.

5.2b Microcytic Anemias

Sommario

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