Sickle Cell Anemia

by Kevin Ahern, PhD

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    00:02 Well, there’s yet one more thing to understand about hemoglobin that’s really critical.

    00:07 And this is a disease known as sickle cell anemia which most people have heard of.

    00:12 Sickle cell anemia is a genetic disease and it affects specifically hemoglobin.

    00:17 There are multiple forms of sickle cell anemia and result form different mutations, but the most common mutation occurs by changing a glutamic acid at position number six to a valine.

    00:30 Now, that very minor change in the structure of a protein causes this hemoglobin to have some very unusual properties.

    00:39 The hemoglobin will tend in these cells to have a polymeric form when the oxygen concentration is low.

    00:49 This polymer of hemoglobin causes the red blood cell that contains it to change its shape.

    00:56 That shape change happens and causes a sickle form of the blood cell as a result of the polymerization of the hemoglobin that I’ve described.

    01:05 Now, you can see on this picture, at the very top, sickled cells.

    01:09 These are cells that have encountered that low oxygen concentration.

    01:13 They’ve had their hemoglobin polymerized and the cell shape has changed accordingly.

    01:19 Well, sickled cells are real problems in the body.

    01:23 Because as the blood cells are traveling through the body, they have to pass through capillaries.

    01:28 Capillaries are where most of the oxygen exchange actually occurs.

    01:34 Rounded red blood cells make it through those capillaries very readily.

    01:38 But the capillaries are where the oxygen is being taken away.

    01:42 It’s in those capillaries where the oxygen concentration will be the lowest, and it’s in those capillaries where the sickling of the red blood cell will happen in a person who has this disease.

    01:52 When that happens, these sickle shapes form, they block the capillaries.

    01:58 The sickled cells get stuck inside of the red blood cells.

    02:01 Now, as you can imagine, this is a pretty nasty thing.

    02:05 First of all, the tissues that contain those capillaries are not getting the oxygen that they need.

    02:10 So a person who has sickle cell anemia will have pain that they will suffer from whenever they exercise heavily because their capillaries are not delivering the oxygen that’s necessary and moreover, they’re being plugged up with these sickled cells.

    02:25 The reason that this disease is called “sickle cell anemia” is that these sickled cells are recognized by the spleen as being damaged.

    02:34 And the spleen’s job is getting rid of damaged blood cells.

    02:38 So even though the cell might be okay when the oxygen concentration comes back to normal, the hemoglobin has caused it to look like the cell is sickled and the spleen says that’s a bad cell and takes it out of circulation.

    02:51 So a person with sickle cell anemia, they’re losing more cells to destruction by their spleen than a person who doesn’t have the disease.

    02:58 And anemia, of course, is a decreased concentration of blood cells.

    03:02 So sickle cell anemia is a very difficult problem.

    03:06 Well, you might ask the question, “Why is sickle cell anemia so widespread? If it’s so deleterious, why wasn’t it selected against? Why do we still see it in the population?” And a lot of people wondering about this question until a few years ago.

    03:21 The question was answered when they started looking at a world map and comparing where the greatest incidents of sickle cell anemia was found, and they contrasted that with where the greatest incidents of malaria was occurring.

    03:35 Now, sickle cell anemia of course is found all around the world today.

    03:39 So I don’t mean to say it’s focused only in Africa because that’s not true.

    03:43 But the reality is, is that sickle cell anemia appears to have given some advantage to people who lived in sub-Saharan Africa.

    03:51 and survived it as a result of surviving malaria.

    03:56 This slide shows the genetics involved in the survival of malaria by people who carry one of the sickle cell genes.

    04:04 Now, to understand this, we have to remember first of all that we each have two sets of chromosomes.

    04:09 One set of chromosomes can have one gene.

    04:13 And the identical set of chromosomes can have a different one.

    04:15 That’s known as heterozygote.

    04:16 So, for example, if I was a carrier of sickle anemia, one of my sets of chromosomes would have a normal unmutated form of hemoglobin.

    04:26 And the other set of my chromosomes would have a mutated form.

    04:30 That’s heterozygous, meaning that they’re different between the two different chromosomes.

    04:35 If I’m homozygous, that would mean that both sets are the same.

    04:40 So I could be homozygous for the mutated form which means both of my chromosomes have the mutated form.

    04:47 Or I could be homozygous for the normal form, the unmutated form in which case both sets of my chromosomes would have the unmutated form.

    04:56 When they compare the survival of people who had been affected with malaria, they found something interesting.

    05:03 What they found was that people who were heterozygous for the sickle cell gene, one copy bad, one copy good, were much more likely to survive malaria as youths than people who were homozygous for the normal or for the defective.

    05:20 There was something about that heterozygous state that protected the person from dying of malaria.

    05:26 This is the reason we think why sickle cell anemia has persisted in the population.

    05:32 There’s a benefit to carrying one gene if you’re living in an area that’s highly infested with malaria.

    05:39 There are no benefits on either other side however.

    05:42 In this presentation, we’ve seen a lot about hemoglobin.

    05:46 We’ve seen how hemoglobin is able to deliver oxygen according to the varying needs of the body and how it response to conditions with protons, with carbon dioxide and with 2,3 BPG, all things that indicate exercise.

    06:00 We’ve also seen how the fetal hemoglobin is different and allows the fetus to have the oxygen that it needs and get that oxygen from mom.

    06:07 And last, we’ve seen the actual advantage of a mutated form of hemoglobin to help people survive malaria.

    About the Lecture

    The lecture Sickle Cell Anemia by Kevin Ahern, PhD is from the course Amino Acid Metabolism.

    Included Quiz Questions

    1. The complications arise from sickled red blood cells getting stuck in capillaries.
    2. The sickling of blood cells occurs upon the binding of oxygen.
    3. The homozygous form of the disease provides the best protection against malaria.
    4. The sickled cells are removed from the circulation by the liver.
    5. Sickled cells move through capillaries easier than normal cells.
    1. The normal glutamic acid present at the 6th position is replaced by valine.
    2. The normal valine present at the 6th position is replaced by glutamic acid.
    3. The normal valine present at the 16th position is replaced by glutamic acid.
    4. The normal glutamic acid present at the 16th position is replaced by valine.
    5. The normal glutamic acid present at the 60th position is replaced by valine.
    1. Polymeric hemoglobin at low oxygen concentrations
    2. Monomeric hemoglobin at low oxygen concentrations
    3. Trimeric hemoglobin at high oxygen concentrations
    4. Dimeric hemoglobin at high oxygen concentrations
    5. Polymeric hemoglobin at high oxygen concentrations
    1. Malaria-prevalent regions of the world
    2. HIV-prevalent regions of the world
    3. Jaundice-prevalent regions of the world
    4. Hepatitis-prevalent regions of the world
    5. Cryptosporidiosis-prevalent regions of the world

    Author of lecture Sickle Cell Anemia

     Kevin Ahern, PhD

    Kevin Ahern, PhD

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    By Noel C. on 06. August 2017 for Sickle Cell Anemia

    he is so good ... I am very thankful to you sir !!