5.2a Microcytic Anemias

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The first of the anemias that we're going to discuss are microcytic anemias.

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In a microcytic anemia,

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the red blood cells are small.

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And this size is actually measured by the

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MCV,

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or the mean corpuscular volume.

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And so the MCV in a microcytic anemia will be less than 80.

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Recall that the normal MCV is anywhere between 80 to 100.

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And so when the cells are small,

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the MCV will be less than 80.

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it is useful to have a little bit of an understanding of how

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the microcytosis occurs,

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because once you understand how the microcytosis occurs,

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you'll get a better understanding of the causes of microcytic anemia.

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So let's go back and remind ourselves that the red blood cell is actually formed

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from a progenitor cell called the erythroblast.

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The erythroblast is basically the cell that produces the red blood cells.

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Now,

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relatively speaking,

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the erythroblast is a large cell.

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and it will divide,

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and then divide,

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and divide,

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and divide,

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and eventually it'll produce small red blood cells.

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So for example,

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if this is the erythroblast,

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it'll divide into two cells,

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and then it'll divide,

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these two cells will each divide into cells.

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And so with each division,

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the cells become smaller.

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And that's important when understanding a microcytic anemia,

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because it helps us to understand why the microcytosis

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is occurring.

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So in particular,

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we should recognize that microcytic anemias occur

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because there is an extra division of the cell.

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i .e.,

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the erythroblast undergoes one extra division,

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or why don't we say that the cells,

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as they're generating from the erythroblast to become mature red

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blood cells, they sort of undergo one extra division.

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Now the next question we could ask is why?

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Why would the red blood cells undergo an extra division?

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And the answer,

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at least the way I think about it,

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is that microcytic anemia is always a problem

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of decreased production of hemoglobin.

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So in each of the microcytic anemias,

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the problem is the decreased production of hemoglobin.

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Now as the red blood cells are developing,

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if there is not enough hemoglobin,

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one way by which the red blood cells can try to maintain the concentration of

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hemoglobin within the red blood cell would be to divide one extra time.

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Another way to think about this is that it is as if the red

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blood cell is trying to produce a nice,

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pretty, red,

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pink cell.

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And if there is not enough hemoglobin,

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there will not be enough pink in the cell.

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And so the red blood cell will divide one extra time in order to try to

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maintain its color,

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i .e.

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the concentration of hemoglobin.

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Okay,

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now with that in mind,

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you then have to understand a little bit of biochemistry to understand the microcytic anemias.

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So let's remind ourselves,

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what is hemoglobin?

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Well, the name gives it away.

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It's heme plus globin.

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Alright, and what is heme?

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Heme is basically iron and protoporphyrin.

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And so,

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if I were to create just a simple understanding in your mind by doing

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the following.

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I've told you that hemoglobin,

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we know that it equals heme plus

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globin.

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Alright,

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and you know that heme is essentially composed of iron.

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plus protoporphyrin,

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just gonna say proto here,

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P -R -O -T -O,

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then if you understand this basic biochemistry,

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it's not hard to recognize the causes of microcytic anemia.

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For example,

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let's say that there is a lack of iron,

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which is called iron deficiency.

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If there's low iron,

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then there would be low heme,

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and if there's low heme,

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there'll be low hemoglobin,

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and if there's low hemoglobin,

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there'll be a microcytic anemia.

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So one cause of a microcytic anemia is iron deficiency anemia.

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Another way by which we could get microcytic anemia would be,

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let's say that there's iron,

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but the iron cannot be used because the patient

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has a chronic inflammatory state,

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and therefore the iron is being stored away in the macrophages.

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So when iron is locked away in the macrophages,

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that is called anemia of chronic disease,

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and the idea there is that iron is not available for use,

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and so therefore if there's low iron,

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then there's gonna be low heme,

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And if there's low heme,

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then there's gonna be low hemoglobin,

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and if there's low hemoglobin,

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there's going to be a microcytic anemia.

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And so the second cause of microcytic anemia is actually anemia of chronic disease.

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The third cause is any circumstance that would decrease the

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production of protoporphyrin.

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And so...

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The disease in which,

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or the anemia in which,

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there is a decreased production of protoporphyrin is called sideroblastic anemia.

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And so in sideroblastic anemia,

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there's low protoporphyrin,

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which results in low heme,

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low heme results in low hemoglobin,

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and low hemoglobin then results in a microcytic anemia.

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And then finally,

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the fourth cause of microcytic anemia is thalassemia.

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And what's thalassemia?

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Thalassemia is when there's decreased production of the globin

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chain.

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Obviously,

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decreased production of the globin chain would result in decreased hemoglobin,

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and decreased hemoglobin would result in a microcytic anemia.

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So actually,

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this is not hard if you understand a little bit of basic biochemistry.

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And there really are four major causes of microcytic anemia.

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Iron deficiency anemia,

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anemia of chronic disease,

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sideroblastic anemia,

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and thalassemia.

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Now that's the global picture that you have to have sort of in your

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mind, and if you keep this picture in your mind,

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you'll be very comfortable when dealing with microcytic anemias.

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There are,

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of course, some details that we have to be familiar with,

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and so we're going to spend the remainder of our time in this section now

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walking through each of these anemias individually and highlighting some important

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high -yield principles.

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So the first of the anemias that we want to discuss is iron deficiency anemia.

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Iron deficiency anemia is due to decreased

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levels of iron within the body.

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This is the most common type of anemia.

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Lack of iron is actually the most common nutritional deficiency in the world.

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The WHO estimates that approximately one -third

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of the entire world's population is deficient in iron,

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and so iron deficiency anemia is something that all of us are going to encounter

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in our patients.

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Now a little bit about the biochemistry of iron.

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You do need to understand it to understand some of the high yields for this

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disease.

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Iron is consumed in both heme,

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which is meat -derived,

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and non -heme,

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which is vegetable -derived,

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forms,

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and the heme form,

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i .e.

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the meat -derived form,

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is more readily absorbed.

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Absorption,

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of course,

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occurs in the duodenum.

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You do need to know that.

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Absorption occurs in the duodenum,

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and it's the enterocyte.

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Recall that the enterocyte,

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histologically,

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is the cell that lines the villi of the duodenum.

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The enterocyte regulates the absorption of iron.

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Basically, the enterocyte takes up iron from the gut and

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then has the ability to transport it into the blood via a

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transporter called ferroportin.

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Now let me draw this for you.

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Let's pretend that this is the enterocyte,

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and this is the lumen of the gut,

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and over here would be a blood vessel.

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The enterocyte basically takes up iron from the gut,

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And then it makes a decision.

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It decides,

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should I send iron into the blood or not?

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The transporter that it uses to

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move iron from the enterocyte into the blood is called ferroportin.

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And this is a key regulatory step in iron biochemistry.

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The idea here is that the body has the

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ability to take up iron,

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but does not have the ability to get rid of iron.

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There really is no way for the body to get rid of iron.

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Now it's true that a little bit of iron gets lost when the skin is turning

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over, and so as skin sloughs off the human being,

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iron is lost,

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a tiny bit of iron is lost.

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And it's also true that a female loses iron through the menstrual cycle.

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However,

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generally speaking,

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physiologically,

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the human body does not really have a way of getting rid of iron.

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And so you only want to bring in iron when

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it's needed by the body,

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and you don't want to allow excess iron to come into the body.

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And so the enterocyte plays that important role of deciding whether

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or not iron should go into the blood.

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And it uses ferroportin to make that decision.

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So ferroportin is the key transporter that takes iron from

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the enterocyte and places it into the blood.

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Now once iron gets into the blood,

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it's always bound.

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Remember that iron has the ability to generate free radicals,

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so it will never be left alone.

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It will always be bound to something.

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In the blood,

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it's bound to a molecule called transferrin.

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And transferrin transports iron and then delivers it to the liver.

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and to the bone marrow macrophages for storage.

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Once iron gets to the liver or the bone marrow macrophages,

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it's stored in the cell,

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but it's stored bound to ferritin.

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So ferritin is the key molecule to which iron is bound when

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it is being stored.

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And again,

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it's important to keep iron bound to ferritin because that binding...

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prevents iron from generating free radicals via the

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fenton reaction.

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And we covered that in detail when we talked about free radicals in chapter

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one of this text.

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Now there are some laboratory measurements that allow you to

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determine the iron status of a patient.

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And these are very high yield to be familiar with,

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both clinically they're useful and obviously on examinations.

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So let's walk through them.

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Now, maybe it would be best to go back and just create a simple diagram

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so we can see what we're actually measuring.

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So again, the idea here is that if you have iron in the blood,

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so this is the blood vessel,

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S… Speaker 1 (5.2a Microcytic Anemias)

iron in the blood is going to be bound to a molecule called transferrin.

10:09

S… Speaker 1 (5.2a Microcytic Anemias)

Now generally speaking,

10:10

S… Speaker 1 (5.2a Microcytic Anemias)

for every three transferrin molecules,

10:13

S… Speaker 1 (5.2a Microcytic Anemias)

one, two,

10:14

S… Speaker 1 (5.2a Microcytic Anemias)

let's make a third one here,

10:15

S… Speaker 1 (5.2a Microcytic Anemias)

for every three transferrin molecules,

10:17

S… Speaker 1 (5.2a Microcytic Anemias)

one of those transferrin molecules will be carrying an iron.

10:22

S… Speaker 1 (5.2a Microcytic Anemias)

Eventually, that iron is delivered to the

10:26

S… Speaker 1 (5.2a Microcytic Anemias)

macrophage.

10:27

S… Speaker 1 (5.2a Microcytic Anemias)

So let's call this the macrophage.

10:28

S… Speaker 1 (5.2a Microcytic Anemias)

And when iron is present within the macrophage,

10:31

S… Speaker 1 (5.2a Microcytic Anemias)

iron is bound to ferritin.

10:34

S… Speaker 1 (5.2a Microcytic Anemias)

So we'll connect it to ferritin over here.

10:36

S… Speaker 1 (5.2a Microcytic Anemias)

Based on this understanding that I've sort of put here on the screen,

10:40

S… Speaker 1 (5.2a Microcytic Anemias)

we can measure a few pieces of information.

10:44

S… Speaker 1 (5.2a Microcytic Anemias)

So for example,

10:45

S… Speaker 1 (5.2a Microcytic Anemias)

if we want to know how much iron is in the blood,

10:47

S… Speaker 1 (5.2a Microcytic Anemias)

we can measure this serum iron.

10:49

S… Speaker 1 (5.2a Microcytic Anemias)

If we want to know how much iron is in the blood,

10:51

S… Speaker 1 (5.2a Microcytic Anemias)

we can measure the serum iron.

10:53

S… Speaker 1 (5.2a Microcytic Anemias)

If we want to know how many transferrin molecules

10:56

S… Speaker 1 (5.2a Microcytic Anemias)

are present in the blood, whether they be bound or not

10:59

S… Speaker 1 (5.2a Microcytic Anemias)

That doesn't matter.

11:00

S… Speaker 1 (5.2a Microcytic Anemias)

If we want to know how many transferrin molecules are present in the blood,

11:03

S… Speaker 1 (5.2a Microcytic Anemias)

we can measure something

11:04

S… Speaker 1 (5.2a Microcytic Anemias)

called the TIBC,

11:06

S… Speaker 1 (5.2a Microcytic Anemias)

which is the total iron binding capacity.

11:09

S… Speaker 1 (5.2a Microcytic Anemias)

It tells you how many transferrin molecules are present in the blood.

11:12

S… Speaker 1 (5.2a Microcytic Anemias)

If you want to know how many of the transferrin molecules are actually bound by

11:16

S… Speaker 1 (5.2a Microcytic Anemias)

iron, we

11:17

S… Speaker 1 (5.2a Microcytic Anemias)

can calculate a percent

11:19

S… Speaker 1 (5.2a Microcytic Anemias)

saturation.

11:20

S… Speaker 1 (5.2a Microcytic Anemias)

Finally,

11:21

S… Speaker 1 (5.2a Microcytic Anemias)

if you want to know how much iron is present in the storage sites,

11:25

S… Speaker 1 (5.2a Microcytic Anemias)

you can measure a serum ferritin.

11:27

S… Speaker 1 (5.2a Microcytic Anemias)

And so ferritin would tell us how much iron is actually present

11:31

S… Speaker 1 (5.2a Microcytic Anemias)

in the bone marrow macrophages and within the liver.

11:34

S… Speaker 1 (5.2a Microcytic Anemias)

So these are four key measurements and they're going to come into play

11:38

S… Speaker 1 (5.2a Microcytic Anemias)

as we move forward in this discussion.

11:41

S… Speaker 1 (5.2a Microcytic Anemias)

Now when we think about iron deficiency,

11:43

S… Speaker 1 (5.2a Microcytic Anemias)

we should understand that deficiency can be caused by a dietary lack or

11:47

S… Speaker 1 (5.2a Microcytic Anemias)

blood loss.

11:48

S… Speaker 1 (5.2a Microcytic Anemias)

These are the two sort of common etiologies of how a patient can become

11:52

S… Speaker 1 (5.2a Microcytic Anemias)

iron deficient.

11:54

S… Speaker 1 (5.2a Microcytic Anemias)

And it's in the context of these two etiologies that I like to think of iron deficiency

11:58

S… Speaker 1 (5.2a Microcytic Anemias)

according to the individual subsets of patients.

12:01

S… Speaker 1 (5.2a Microcytic Anemias)

So for example,

12:02

S… Speaker 1 (5.2a Microcytic Anemias)

in an infant,

12:03

S… Speaker 1 (5.2a Microcytic Anemias)

an important cause of iron deficiency would be breastfeeding.

12:06

S… Speaker 1 (5.2a Microcytic Anemias)

And that's because breast milk contains

12:09

S… Speaker 1 (5.2a Microcytic Anemias)

little to no iron,

12:10

S… Speaker 1 (5.2a Microcytic Anemias)

and so infants can become iron deficient when they're breastfeeding.

12:14

S… Speaker 1 (5.2a Microcytic Anemias)

In a child,

12:15

S… Speaker 1 (5.2a Microcytic Anemias)

iron deficiency can arise if there's a poor diet,

12:18

S… Speaker 1 (5.2a Microcytic Anemias)

and so children,

12:19

S… Speaker 1 (5.2a Microcytic Anemias)

they're growing,

12:20

S… Speaker 1 (5.2a Microcytic Anemias)

they need iron,

12:21

S… Speaker 1 (5.2a Microcytic Anemias)

and sometimes the diet is not appropriate for that growth,

12:24

S… Speaker 1 (5.2a Microcytic Anemias)

and so children can become iron deficient.

12:27

S… Speaker 1 (5.2a Microcytic Anemias)

due to poor diet.

12:29

S… Speaker 1 (5.2a Microcytic Anemias)

In adults,

12:30

S… Speaker 1 (5.2a Microcytic Anemias)

important classic causes of iron deficiency in a male,

12:34

S… Speaker 1 (5.2a Microcytic Anemias)

you think about peptic ulcer disease,

12:36

S… Speaker 1 (5.2a Microcytic Anemias)

that's actually the most common cause in a middle -aged male,

12:39

S… Speaker 1 (5.2a Microcytic Anemias)

and the most common cause in a middle -aged female would be menorrhagia,

12:43

S… Speaker 1 (5.2a Microcytic Anemias)

which is heavy menstrual bleeding,

12:44

S… Speaker 1 (5.2a Microcytic Anemias)

in which iron would be lost because blood is lost,

12:46

S… Speaker 1 (5.2a Microcytic Anemias)

or pregnancy.

12:47

S… Speaker 1 (5.2a Microcytic Anemias)

In pregnancy,

12:48

S… Speaker 1 (5.2a Microcytic Anemias)

a woman needs a large amount of iron to grow the fetus,

12:52

S… Speaker 1 (5.2a Microcytic Anemias)

and so these are two common causes in middle -aged adults.

12:55

S… Speaker 1 (5.2a Microcytic Anemias)

In older adults,

12:56

S… Speaker 1 (5.2a Microcytic Anemias)

common causes in the Western world are colon polyps or

13:00

S… Speaker 1 (5.2a Microcytic Anemias)

carcinoma.

13:01

S… Speaker 1 (5.2a Microcytic Anemias)

And in older adults,

13:03

S… Speaker 1 (5.2a Microcytic Anemias)

the most common cause in the developing world is actually a hookworm.

13:07

S… Speaker 1 (5.2a Microcytic Anemias)

And if we go back to microbiology,

13:11

S… Speaker 1 (5.2a Microcytic Anemias)

recall that the two hookworms to be familiar with,

13:13

S… Speaker 1 (5.2a Microcytic Anemias)

one is a Nicator and the other is Ancelostema.

13:17

S… Speaker 1 (5.2a Microcytic Anemias)

And so Nicator and Ancelostema are two hookworms that are common

13:22

S… Speaker 1 (5.2a Microcytic Anemias)

causes of

13:23

S… Speaker 1 (5.2a Microcytic Anemias)

iron deficiency,

13:24

S… Speaker 1 (5.2a Microcytic Anemias)

again because of the blood loss associated with hookworms,

13:27

S… Speaker 1 (5.2a Microcytic Anemias)

these are common causes of iron deficiency in the developing

13:31

S… Speaker 1 (5.2a Microcytic Anemias)

world.

13:33

S… Speaker 1 (5.2a Microcytic Anemias)

There are some other causes to be aware of.

13:35

S… Speaker 1 (5.2a Microcytic Anemias)

Obviously,

13:36

S… Speaker 1 (5.2a Microcytic Anemias)

malnutrition could result in iron deficiency,

13:40

S… Speaker 1 (5.2a Microcytic Anemias)

but we kind of highlighted that with the notion of poor diet in a child.

13:43

S… Speaker 1 (5.2a Microcytic Anemias)

Malabsorption could result in iron deficiency.

13:47

S… Speaker 1 (5.2a Microcytic Anemias)

Let's say that a patient has a disease that disrupts the duodenum,

13:51

S… Speaker 1 (5.2a Microcytic Anemias)

like celiac disease,

13:52

S… Speaker 1 (5.2a Microcytic Anemias)

in which the villi of the duodenum are destroyed.

13:55

S… Speaker 1 (5.2a Microcytic Anemias)

That can result in a certain degree of malabsorption,

13:58

S… Speaker 1 (5.2a Microcytic Anemias)

and if there's malabsorption,

13:59

S… Speaker 1 (5.2a Microcytic Anemias)

the patient could obviously become

14:02

S… Speaker 1 (5.2a Microcytic Anemias)

And then a third example would be gastrectomy.

14:05

S… Speaker 1 (5.2a Microcytic Anemias)

And this actually is a kind of high yield example.

14:07

S… Speaker 1 (5.2a Microcytic Anemias)

And the reason this is high yield is because it goes back to a

14:11

S… Speaker 1 (5.2a Microcytic Anemias)

little bit of biochemistry concerning iron.

14:13

S… Speaker 1 (5.2a Microcytic Anemias)

And that is that iron can be present in an Fe2 plus state.

14:17

S… Speaker 1 (5.2a Microcytic Anemias)

It can also be present in an Fe3 plus state.

14:21

S… Speaker 1 (5.2a Microcytic Anemias)

And it's the Fe2 plus that is better,

14:25

S… Speaker 1 (5.2a Microcytic Anemias)

that is more easily absorbed by the body.

14:27

S… Speaker 1 (5.2a Microcytic Anemias)

And the way I remember that,

14:29

S… Speaker 1 (5.2a Microcytic Anemias)

a little funny,

14:30

S… Speaker 1 (5.2a Microcytic Anemias)

but the way I remember that is Fe2 goes into the body.

14:34

S… Speaker 1 (5.2a Microcytic Anemias)

Fe2 goes into the body.

14:36

S… Speaker 1 (5.2a Microcytic Anemias)

Why is that important for this discussion of gastrectomy?

14:40

S… Speaker 1 (5.2a Microcytic Anemias)

Well, the idea is that acid maintains the Fe2 plus

14:44

S… Speaker 1 (5.2a Microcytic Anemias)

state.

14:44

S… Speaker 1 (5.2a Microcytic Anemias)

And so if there is acidity,

14:46

S… Speaker 1 (5.2a Microcytic Anemias)

the Fe2 remains in the two,

14:48

S… Speaker 1 (5.2a Microcytic Anemias)

the iron remains in the two plus state.

14:51

S… Speaker 1 (5.2a Microcytic Anemias)

and by remaining in the 2 -plus state,

14:52

S… Speaker 1 (5.2a Microcytic Anemias)

it's more readily absorbed.

14:53

S… Speaker 1 (5.2a Microcytic Anemias)

Gastrectomy,

14:55

S… Speaker 1 (5.2a Microcytic Anemias)

where a patient would lose part of the stomach,

14:58

S… Speaker 1 (5.2a Microcytic Anemias)

may result in decreased...

15:00

S… Speaker 1 (5.2a Microcytic Anemias)

and the decreased acid would result in decreased bioavailability

15:04

S… Speaker 1 (5.2a Microcytic Anemias)

of iron because less iron would be in the two plus state.

15:07

S… Speaker 1 (5.2a Microcytic Anemias)

So this becomes important again because it ties into a little bit of biochemistry.

15:14

S… Speaker 1 (5.2a Microcytic Anemias)

When a patient becomes iron deficient,

15:16

S… Speaker 1 (5.2a Microcytic Anemias)

they actually go through a series of phases.

15:17

S… Speaker 1 (5.2a Microcytic Anemias)

And it's nice to understand these phases

15:22

S… Speaker 1 (5.2a Microcytic Anemias)

or stages because they will help you to better understand what's going

15:26

S… Speaker 1 (5.2a Microcytic Anemias)

on in iron deficiency.

15:27

S… Speaker 1 (5.2a Microcytic Anemias)

So I'm actually going to take a moment to walk you through each of these.

15:30

S… Speaker 1 (5.2a Microcytic Anemias)

Now the very first thing,

15:31

S… Speaker 1 (5.2a Microcytic Anemias)

let's pretend that there's a normal patient and they've got normal iron and they're doing

15:35

S… Speaker 1 (5.2a Microcytic Anemias)

fine.

15:36

S… Speaker 1 (5.2a Microcytic Anemias)

And then let's say that the patient,

15:38

S… Speaker 1 (5.2a Microcytic Anemias)

I don't know, they get a hookworm infection and so now they're starting to lose blood.

15:43

S… Speaker 1 (5.2a Microcytic Anemias)

So what's going to happen is that initially,

15:45

S… Speaker 1 (5.2a Microcytic Anemias)

as the bone marrow is trying to make red blood cells,

15:49

S… Speaker 1 (5.2a Microcytic Anemias)

it's going to use up the stored iron.

15:51

S… Speaker 1 (5.2a Microcytic Anemias)

That's the very first thing that it will do when there isn't sufficient iron being brought

15:56

S… Speaker 1 (5.2a Microcytic Anemias)

into the body.

15:57

S… Speaker 1 (5.2a Microcytic Anemias)

So over time,

15:59

S… Speaker 1 (5.2a Microcytic Anemias)

the very early stage of iron deficiency is that the storage

16:03

S… Speaker 1 (5.2a Microcytic Anemias)

iron will be depleted.

16:04

S… Speaker 1 (5.2a Microcytic Anemias)

Now recall,

16:05

S… Speaker 1 (5.2a Microcytic Anemias)

what is the measure of storage iron?

16:08

S… Speaker 1 (5.2a Microcytic Anemias)

Ferritin.

16:09

S… Speaker 1 (5.2a Microcytic Anemias)

Ferritin tells you how much iron is stored in the body.

16:12

S… Speaker 1 (5.2a Microcytic Anemias)

Now,

16:12

S… Speaker 1 (5.2a Microcytic Anemias)

when the storage iron is depleted,

16:14

S… Speaker 1 (5.2a Microcytic Anemias)

what is going to happen to the ferritin,

16:17

S… Speaker 1 (5.2a Microcytic Anemias)

the serum ferritin?

16:18

S… Speaker 1 (5.2a Microcytic Anemias)

Then the serum ferritin is going to go down,

16:22

S… Speaker 2 (5.2a Microcytic Anemias)

correct?

16:24

S… Speaker 1 (5.2a Microcytic Anemias)

because the storage iron is being consumed.

16:27

S… Speaker 1 (5.2a Microcytic Anemias)

And as the serum ferritin goes down,

16:29

S… Speaker 1 (5.2a Microcytic Anemias)

one of the other things to bear in mind is that sort of always

16:34

S… Speaker 1 (5.2a Microcytic Anemias)

opposite of what ferritin does is TIBC.

16:36

S… Speaker 1 (5.2a Microcytic Anemias)

So whenever the ferritin goes down,

16:38

S… Speaker 1 (5.2a Microcytic Anemias)

the total iron binding capacity is

16:42

S… Speaker 1 (5.2a Microcytic Anemias)

going to go up.

16:43

S… Speaker 1 (5.2a Microcytic Anemias)

And what is the total iron binding capacity measuring again?

16:46

S… Speaker 1 (5.2a Microcytic Anemias)

It's measuring transferrin.

16:48

S… Speaker 1 (5.2a Microcytic Anemias)

This sort of makes sense in my mind.

16:51

S… Speaker 1 (5.2a Microcytic Anemias)

Whenever the ferritin is down,

16:53

S… Speaker 1 (5.2a Microcytic Anemias)

Then the macrophages and the liver will sort of recognize that

16:57

S… Speaker 1 (5.2a Microcytic Anemias)

the ferritin is down,

16:58

S… Speaker 1 (5.2a Microcytic Anemias)

particularly because one of the storage sites of iron is the liver,

17:01

S… Speaker 1 (5.2a Microcytic Anemias)

and then the liver will begin to pump out more transferrin molecules to

17:05

S… Speaker 1 (5.2a Microcytic Anemias)

go and try to find more iron.

17:07

S… Speaker 1 (5.2a Microcytic Anemias)

And so any time the ferritin goes down,

17:10

S… Speaker 1 (5.2a Microcytic Anemias)

the TIBC,

17:11

S… Speaker 1 (5.2a Microcytic Anemias)

which is a measure of the number of transferrin molecules,

17:13

S… Speaker 1 (5.2a Microcytic Anemias)

will go up.

17:14

S… Speaker 1 (5.2a Microcytic Anemias)

General principle,

17:15

S… Speaker 1 (5.2a Microcytic Anemias)

always,

17:16

S… Speaker 1 (5.2a Microcytic Anemias)

when the ferritin goes down,

17:18

S… Speaker 1 (5.2a Microcytic Anemias)

the TIBC will go up.

17:21

S… Speaker 1 (5.2a Microcytic Anemias)

So that's really the first stage of iron deficiency.

17:24

S… Speaker 1 (5.2a Microcytic Anemias)

Once the stored iron is used,

17:26

S… Speaker 1 (5.2a Microcytic Anemias)

then the next thing that's going to happen is the serum iron is going to be

17:31

S… Speaker 1 (5.2a Microcytic Anemias)

consumed.

17:31

S… Speaker 1 (5.2a Microcytic Anemias)

And as the serum iron is going to be consumed,

17:34

S… Speaker 1 (5.2a Microcytic Anemias)

a few things are going to happen according to your laboratory studies.

17:37

S… Speaker 1 (5.2a Microcytic Anemias)

Number one,

17:38

S… Speaker 1 (5.2a Microcytic Anemias)

the serum iron will go down,

17:40

S… Speaker 1 (5.2a Microcytic Anemias)

because as serum iron is being used,

17:43

S… Speaker 1 (5.2a Microcytic Anemias)

obviously its levels are going to go down.

17:45

S… Speaker 1 (5.2a Microcytic Anemias)

And number two,

17:46

S… Speaker 1 (5.2a Microcytic Anemias)

the percent saturation of iron will actually

17:50

S… Speaker 1 (5.2a Microcytic Anemias)

also go down.

17:52

S… Speaker 1 (5.2a Microcytic Anemias)

Now the way to remember this is to just think about it.

17:54

S… Speaker 1 (5.2a Microcytic Anemias)

So let's remind ourselves that if you have transferrin molecules,

17:57

S… Speaker 1 (5.2a Microcytic Anemias)

okay, let's draw here six transferrin molecules.

18:01

S… Speaker 1 (5.2a Microcytic Anemias)

So one, two,

18:02

S… Speaker 1 (5.2a Microcytic Anemias)

three, four.

18:03

S… Speaker 1 (5.2a Microcytic Anemias)

Five, six.

18:04

S… Speaker 1 (5.2a Microcytic Anemias)

We've got six transferrin molecules,

18:06

S… Speaker 1 (5.2a Microcytic Anemias)

correct?

18:07

S… Speaker 1 (5.2a Microcytic Anemias)

Now normally,

18:08

S… Speaker 1 (5.2a Microcytic Anemias)

when you think about transferrin,

18:10

S… Speaker 1 (5.2a Microcytic Anemias)

one out of every three is bound to iron.

18:12

S… Speaker 1 (5.2a Microcytic Anemias)

So one out of every three is bound to iron.

18:15

S… Speaker 1 (5.2a Microcytic Anemias)

So it looks like this.

18:16

S… Speaker 1 (5.2a Microcytic Anemias)

Now if one out of every three is bound to iron,

18:19

S… Speaker 1 (5.2a Microcytic Anemias)

then what's the normal percent saturation?

18:21

S… Speaker 1 (5.2a Microcytic Anemias)

Well,

18:22

S… Speaker 1 (5.2a Microcytic Anemias)

in this particular case,

18:23

S… Speaker 1 (5.2a Microcytic Anemias)

we've got two molecules of iron and six molecules of transferrin.

18:26

S… Speaker 1 (5.2a Microcytic Anemias)

So the current saturation,

18:28

S… Speaker 1 (5.2a Microcytic Anemias)

I'm going to draw it up here in the left -hand side of your slide,

18:30

S… Speaker 1 (5.2a Microcytic Anemias)

is going to be two over six.

18:33

S… Speaker 1 (5.2a Microcytic Anemias)

which really equals one -third,

18:34

S… Speaker 1 (5.2a Microcytic Anemias)

which equals 33%,

18:37

S… Speaker 1 (5.2a Microcytic Anemias)

which is the normal percent saturation.

18:39

S… Speaker 1 (5.2a Microcytic Anemias)

All right,

18:40

S… Speaker 1 (5.2a Microcytic Anemias)

so the normal percent saturation is 33%.

18:42

S… Speaker 1 (5.2a Microcytic Anemias)

Now let's assume that the patient is becoming iron deficient and

18:46

S… Speaker 1 (5.2a Microcytic Anemias)

the serum iron is depleted.

18:48

S… Speaker 1 (5.2a Microcytic Anemias)

Well, if this iron molecule is consumed,

18:51

S… Speaker 1 (5.2a Microcytic Anemias)

now only one out of six transferrin

18:55

S… Speaker 1 (5.2a Microcytic Anemias)

molecules is bound by iron,

18:56

S… Speaker 1 (5.2a Microcytic Anemias)

and so one over six equals...

19:00

S… Speaker 1 (5.2a Microcytic Anemias)

you know 16 % roughly and so you can see that the percent

19:05

S… Speaker 1 (5.2a Microcytic Anemias)

saturation has gone down when serum iron is depleted the serum

19:09

S… Speaker 1 (5.2a Microcytic Anemias)

iron will go down and the percent saturation will also go down so that's

19:13

S… Speaker 1 (5.2a Microcytic Anemias)

the next phase of iron deficiency

19:17

S… Speaker 1 (5.2a Microcytic Anemias)

Now the third stage or phase of iron deficiency is normal citic

19:21

S… Speaker 1 (5.2a Microcytic Anemias)

anemia.

19:21

S… Speaker 1 (5.2a Microcytic Anemias)

So what's the idea here?

19:22

S… Speaker 1 (5.2a Microcytic Anemias)

Now as iron is being depleted from the storage sites,

19:25

S… Speaker 1 (5.2a Microcytic Anemias)

and as iron is being depleted from the serum,

19:28

S… Speaker 1 (5.2a Microcytic Anemias)

the bone marrow is still going to continue to try to make red blood cells.

19:31

S… Speaker 1 (5.2a Microcytic Anemias)

And in order to make red blood cells,

19:33

S… Speaker 1 (5.2a Microcytic Anemias)

it needs to produce heme.

19:34

S… Speaker 1 (5.2a Microcytic Anemias)

And in order to produce heme,

19:36

S… Speaker 1 (5.2a Microcytic Anemias)

it's going to need iron.

19:37

S… Speaker 1 (5.2a Microcytic Anemias)

And so as the bone marrow begins to recognize that iron isn't available,

19:41

S… Speaker 1 (5.2a Microcytic Anemias)

It'll make a sacrifice.

19:42

S… Speaker 1 (5.2a Microcytic Anemias)

It'll say,

19:43

S… Speaker 1 (5.2a Microcytic Anemias)

I prefer to make normal red blood cells.

19:46

S… Speaker 1 (5.2a Microcytic Anemias)

I want nice,

19:47

S… Speaker 1 (5.2a Microcytic Anemias)

pretty,

19:48

S… Speaker 1 (5.2a Microcytic Anemias)

red,

19:48

S… Speaker 1 (5.2a Microcytic Anemias)

beautiful red blood cells.

19:50

S… Speaker 1 (5.2a Microcytic Anemias)

However,

19:51

S… Speaker 1 (5.2a Microcytic Anemias)

because I can't make as many as I would like,

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S… Speaker 1 (5.2a Microcytic Anemias)

I'll just make less.

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S… Speaker 1 (5.2a Microcytic Anemias)

And so initially,

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S… Speaker 1 (5.2a Microcytic Anemias)

the patient will actually get a normal psittic anemia.

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S… Speaker 1 (5.2a Microcytic Anemias)

will be normal in size,

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S… Speaker 1 (5.2a Microcytic Anemias)

but there will be less of them made,

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S… Speaker 1 (5.2a Microcytic Anemias)

and so the patient will actually develop a normalcytic anemia.

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S… Speaker 1 (5.2a Microcytic Anemias)

The very early stage of iron deficiency anemia is actually

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S… Speaker 1 (5.2a Microcytic Anemias)

normalcytic,

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S… Speaker 1 (5.2a Microcytic Anemias)

and examiners like you to know that,

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S… Speaker 1 (5.2a Microcytic Anemias)

because they want you to understand the sequence of what's going on.

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S… Speaker 1 (5.2a Microcytic Anemias)

And by the way,

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S… Speaker 1 (5.2a Microcytic Anemias)

clinically this is important as well,

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S… Speaker 1 (5.2a Microcytic Anemias)

because you may find patients in your practice that are in very early stages

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S… Speaker 1 (5.2a Microcytic Anemias)

of iron deficiency,

20:22

S… Speaker 1 (5.2a Microcytic Anemias)

then you need to know that the initial stage of iron deficiency is actually a

5.2a Microcytic Anemias

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