Beta Thalassemia; Causes and Types

Beta Thalassemia; Causes and Types

Beta Thalassemia; Causes and Types

Beta Thalassemia; Causes and Types All right welcome back, so we have been talking about anemia, microcytic anemia, now we’re talking about Thalassemia…in the last video we have talked about alpha-thalassemia (link in description). Today. We’ll talk about beta thalassemia So, Beta Thalassemia is microcytic anemia, and again symptoms of anemia Tired and pale, pale and tired…sometimes, I have murmur (flow murmur), sometimes I can get angina. also… exercise intolerance, fatigue, Etc. Beta thalassemia is very common in Italy so keep that in mind, okay? So, as you know… Hemoglobin has two alpha subunits, and two beta subunits…good They are called tetramers excellent Thalassemia by definition is a defect in globin chain synthesis good, so this will lead to two things; here you have the globin so Decreased globin synthesis will lead to decreased hemoglobin i.e. anemia Good…what else? when globin chain Synthesis unbalanced hemo tetramers form so for example when alpha is not present beta will form tetramers They are insoluble They will precipitate in RBC’s. The spleen macrophages will recognize that and will cause hemolysis Will destroy these abnormal RBCs. this will lead to… ineffective erythropoiesis Why? -Bone marrow tries to respond to the hemolysis by producing more… red blood cells. However, Globin synthesis decreas; I cannot synthesize Good RBC’s, or sufficient RBC’s. It’s called ineffective erythropoiesis beta thalassemia The problem is in chromosome 11 Do you remember what chromosome was involved in alpha-thalassemia? Correct! – 16 …Okay, how to remember beta and 1? -just draw beta like this: And then draw an 11 like this. Okay, so we can do it better. This is the 11 and then this is the beta, like this. Just any way to remember, okay, it’s common in the Mediterranean, Middle Eastern and Asian population…Please, remember Greece and Italy. Greece and Italy beta-thalassemia chromosome 11 Beta thalassemia can be mild or severe Mild anemia usually due to a splicing defect Go back to your Molecular Biology and review this topic. Severe anemia is due to a specific type of point mutation, called: nonsense mutation There is a stop codon. Okay? That’s introduced… Earlier than usual. Stop codons are these as you know this will lead to termination… Of protein synthesis, and in this case the protein is the beta globin -in = protein So, genetically speaking beta thalassemia can be either heterozygous or Homozygous Heterozygous is beta thalassemia minor homozygous can be either: thalassemia intermediate or beta thalassemia major chromosome 11 so, number one beta-thalassemia minor there is Increase in the number of microcytic RBCs, of course. Thalassemia is a microcytic anemia. However, in thalassemia, There is increased number of RBC’s. Nobody know why!!! That’s interesting so when you have microcytic anemia low hemoglobin, low hematocrit, but, (and that’s a big but) RBC count is a little bit high Iron studies are normal, please suspect thalassemia. Beta thalassemia minor; it’s minor, so it’s either asymptomatic or there is minor anemia So what will happen to the normal adult hemoglobin A? – it will slightly decrease Hemoglobin A2 will increase, hemoglobin F will slightly increase. so, Hemoglobin electrophoresis will show this. Hemoglobin electrophoresis in beta thalassemia minor is… abnormal Contrast that with the minor form of alpha-thalassemia, called: the Alpha thalassemia trait Trait you remember? Trait, where the hemoglobin electrophoresis was completely normal! Alrighty, now the big one; Beta thalassemia major (also known as Cooley’s anemia) so, we start here by a problem in the Beta globin production… Zero; there is none whatsoever; no beta globin production. So what else do we have other than the beta? -Alpha… Alpha globin will form and precipitate forming… Homo-tetramers, and these homotetramers will lead to two things: first in the bone marrow… the RBC’s containing the Homotetramers will die… Earlier before being released… why? – they are not healthy, they cannot survive. So, they die… This is called ineffective Erythropoiesis, as you know. What else will happen to these… homotetramers? – they will precipitate in RBCs, so the Macrophage in the spleen will recognize these Oh, these are ill, abnormal RBCs, let’s kill them!!! :O So, they destroy the RBC’, which leads to hemolytic anemia. Hemolytic anemia? – the kidney will respond by increasing Erythropoietin production erythropoietin will lead to something called… Erythroid hyperplasia Erythroid is the cell line that produces RBC’s and… hyperplasia means increasing the number of cells, so we increased number of RBC’s and… We increase the formation, increased production in the bone marrow… This is called: medullary erythropoiesis Fine. But, I need more, I need more factories to produce more RBC’s, so the spleen and the liver , or the reticulo-endothelial organs will take over. It’s called extra-medullary Hematopoiesis. They will start forming new RBCs Ok, they are working really hard. They will enlarge… “hepatosplenomegaly” Fine, the medullary cavity inn the skull, and in the bones will enlarge. When they enlarge, This will include the skull who give us an appearance on x-ray called hair on end appearance or crew-cut skull Crew-cut-hair skull Also, the maxilla: the maxillary bone will enlarge leading to something called chipmunk facies fine! So, hemolytic anemia…so we need to give the patient blood. Giving them blood? -we will make them dependent on the transfusion or transfusion-dependent This blood contains iron, which will lead to iron overload… Hemosiderosis and secondary hemochromatosis…What else? anemia; hemolytic anemia is destruction of the Hemoglobin, and hemoglobin has heme and globin. Haeme has iron and protoporphyrin. Protoporphyrin will convert to unconjugated bilirubin, goes to the liver to be Conjugated into the conjugated bilirubin Okay, so this increase in unconjugated bilirubin Will lead to unconjugated hyperbilirubinemia and of course jaundice! That’s it for beta thalassemia major…if you understand this slide, you will know a lot of information for your exam 🙂 Now, the last one: Beta thalassemia intermedia It’s an intermediate form it’s not as severe as major, but it’s also more severe than the minor beta thalassemia So there is an a Co-inheritance with alpha thalassemia trait. so, when you have beta thalassemia intermedia, usually you have also alpha-thalassemia trait fine! Okay, so there is also minor Qualitative defect in the beta globin, so usually we have alpha and beta Remember in beta thalassemia major, we don’t have any beta. So, the Alpha Increased forming Homotetramers. However in this condition. I have also alpha-thalassemia trait I have Deficiency in this alpha globin chains, so I cannot increase them as much I cannot Produce as much homotetramers, so there is less homotetramers Than beta thalassemia major…There is less Hemolysis, and of course, hemoglobin F Will increase since you don’t have beta. What will happen? -Gamma change will form when you have alpha and gamma. This is called Hemoglobin F, the fetal hemoglobin. Okay, that’s it for thalassemia, guys I’ll see in the next video, but please subscribe like us on Facebook and follow us on Twitter Thank you very much