Transcription
We are back. Sickle-cell disease. Apparently, my hematology videos are the most loved, so we will continue. Okay. Sickle-cell disease is a problem, or a disease, when your blood cells—your red blood cells—now look like a sickle. And no, I'm not talking about communism. Okay.
Sickle-cell disease is prevalent in sub-Saharan Africa. So they call this part of Africa the Sahara, and beneath it is the sub-Saharan Africa. So here we have the sickle-cell disease problem. Why is that so? The theory goes like this: through evolution, since we have a lot of malaria in Africa, we have developed a process, through natural selection, to protect us from the nasty Plasmodium falciparum malaria. Okay. So how are we going to do that? We will sickle our red blood cells so that the malaria now cannot infect us. Okay. This is the Anopheles mosquito. Alright, so through evolution, we will sickle our red blood cells so that the Plasmodium cannot infect them. It's common in African Americans and in the Black population in general. Symptoms of anemia will be the same: tired and pale, pale and tired. Sometimes I have angina, sometimes I have a murmur, and also headaches, exercise intolerance, fatigue, etc. Okay.
What's different here? It can both infect kids as well as adults. The disease process can be similar, but the complications may be a little bit different. So bear with me. And by the way, you have a smiley face here because Egypt is my home country. Okay, at least something to be proud of.
Sickle-cell disease is an autosomal recessive disease. Okay, so it goes like this: we have mom and dad as carriers. They will give birth to children. 25% of the kids will be normal; they are not carriers, they are not abnormal; these are fine, normal kids. 50%, or half of their offspring, will be carriers of the sickle-cell disease, so that we call them carriers, or we call them sickle-cell trait, or hemoglobin AS. These are carriers. Since it's an autosomal recessive, we need to have both of the alleles S okay, in order to present itself as symptoms. So just AS cannot produce symptoms because it's a recessive disease. It's an autosomal recessive; it needs those two copies or recessive so that you can have the symptoms of the disease. Abnormal? Yes. Sickle-cell disease? Yes. Hemoglobin SS? Yes. Those are the 25%. Again, the sub-Saharan Africa. How about the carrier, or the sickle-cell trait? Do they get the same sickling? No. It's very rare that their blood cells will sickle. What's the point then? Again, evolutionary protection against the Plasmodium falciparum malaria.
In a previous video, I've discussed the hemoglobin structure. So the hemoglobin structure has four subunits, four hemoglobin chains. Okay. Each one has a protein part, the globin chains, and the non-protein parts, the heme. Okay. The heme itself has two parts: the porphyrin and iron in the ferrous state. That's fine. Each subunit has a molecular weight of sixteen thousand. The adult hemoglobin, or hemoglobin A, has a molecular weight of around sixty-four thousand. Again, that's not important, but remember hemoglobin has four subunits or four chains. Each of these chains, or each heme molecule, will carry one oxygen molecule—not an atom; it carries two atoms in the molecular form of oxygen. Please remember oxygen is bound to hemoglobin loosely and reversibly. So loosely, which means that it's easily dissociated from the hemoglobin. And this was the story of the hemoglobin dissociation curve, as you know.
And now to the big picture. So we have here your normal hemoglobin: two alpha chains and two beta chains. Where is the problem in sickle-cell disease? Defect in the beta globin chains. What's the issue here? Usually, or normally, you have your amino acid sequence, and in position number six you have an amino acid called glutamine, which is hydrophilic—nice. Instead, in sickle-cell disease, you have a valine in the position of glutamine. So instead of glutamine, now we have valine. Valine is hydrophobic, so there is a problem. This mutation is a non-conservative one. Why is that? Because the glutamine was hydrophilic, the valine is hydrophobic; the yield is different. It's a non-conservative mutation. Also, it's a missense mutation. Why? Because a single nucleotide changed, which resulted in a codon that codes for a different amino acid. So instead of glutamine, now we have valine. The missense mutation is a subtype of point mutation. So if the question asks you, is it conservative or not? It's non-conservative. What type of mutation? If missense is one of the choices, pick it. If point mutation is there, please choose it. Okay.
Now, what will happen is this: valine in this place will cause the hemoglobin to change its shape when present in a low-oxygen environment. So if this hemoglobin is deoxygenated, it will start to sickle like this. So oxygen: no sickle; no oxygen: sickle. The deoxygenated form is the one causing sickling. When we have oxygen, usually there is no problem. So the cycle goes like this: you have no oxygen, and you have this non-conservative missense mutation, so your red blood cell will start to sickle in this low-oxygen environment. Repeated sickling will lead to membrane damage of that red blood cell. This will lead to hemolysis; the red blood cells are destroyed, which will lead to no oxygen. Why? Because who carries your oxygen? The red blood cell, but now they are getting destroyed, so you're ending up with no oxygen, and no oxygen will lead to sickling, and on and on and on—a vicious cycle. That's why, once the sickle-cell process starts, it's really getting worse and worse, and it's very hard to stop. If you would like to stop it at this stage, you give oxygen, because oxygen will lead to no sickling. So that's why prevention is better than cure, but it's really hard to tell. Okay. Please keep this in mind. This is sickle-cell disease. Sickle-cell trait is different, and we will talk about that later.
Now, to the oxygen dissociation curve. Here is your normal, nice oxygen curve, and it's being shifted to the right. Shift to the right means that your hemoglobin is releasing oxygen to the tissue. So right is release. Anything that will lead to a right shift of the curve, which means that oxygen is leaving the hemoglobin, will lead to sickling, because no oxygen equals sickling of this hemoglobin—the defected hemoglobin in the beta globin chains due to a non-conservative point mutation. Nice and simple. It will take us a lot of videos to discuss all of the sickle-cell disease, but I'd like you to know everything about it. It's a very high-yield topic because it cuts through a lot of disciplines: you have physiology, you have pathology, you have internal medicine, you have biochemistry—a lot of disciplines. That's why the exams love sickle-cell disease, and we love them too. See you in the next video.