Disorders of RBCs / Robbins Pathology : Macrocytic anemias, Microcytic anemias & Normocytic anemias

Hey guys, welcome back. Now, in this class, I'm going to start with the amount path. Okay? Now, in this class, I'll be starting with the RBC results. The later classes will be discussing about the platelet disorders as well as the WBC disorders. Okay? Now, in this class, let's begin with the RBC results. The main RBC result that everyone knows is anemia. How many types of anemia are there, sir? There are three types of anemia: microcytic, macrocytic, and normocytic anemias. So, in this class, let's try to complete as many anemias as possible. Let's try to discuss like what are the main pathologies involved in the development of these anemias. Okay? Having said that, now without any further late, let's begin our topic RBC disorders. Say, in the RBC disorders, first the topic I am taking here is anemias. Okay? So, what exactly is anemia, sir? Okay? So, anemia in males, the males, the hemoglobin, okay, the amount of hemoglobin, if it is less than 13.5 grams per deciliter. So, in the male, if the hemoglobin level, if it is less than 13.5 grams per deciliter, deciliter, misrememberable. So, in 100 ml of blood, okay, in 100 ml of blood, if the hemoglobin, if it is less than the hemoglobin, the pigment, okay, the pigmented protein, if it is less than 13.5 grams per deciliter, then it should be considered as anemia in the males. The same females, if the hemoglobin, if it's less than 12.5 grams per deciliter, in females, sir, if the hemoglobin is, if it is less than 12.5 grams per deciliter, then it's considered as anemia in females. So, once a patient is having anemia, what kind of symptoms are going to be seen in the patient? Okay? Imagine I'm the one who is having anemia, what kind of symptoms are going to be seen? Say, it's a hemoglobin which is bringing the oxygen to the tissues. Where less amount of hemoglobin is there, veins definitely there is going to be hypoxia. Anemic hypoxia is going to occur, right? So, the patient is going to have hypoxic symptoms. Okay? The patient is going to have hypoxic symptoms. So, what are these hypoxic symptoms? So, the oxygen is not properly getting delivered to the tissues. The adequate amount of oxygen is not properly going to the tissues. So, hypoxia is there. So, the hypoxia symptoms are going to be weakness, very easily the patient is getting weak and fatigue. Okay? Weakness or fatigability, easy fatigability. Okay? Easy fatigue. The patient is going to have easy fatigue, and the patient is going to have dyspnea kind of symptoms. The patient is going to have headaches, like lightheadedness can be seen. Okay? Lightheadedness. See, the point which I want you to know is, these symptoms are going to be the same. These symptoms are going to be the same for all kinds of anemia. It doesn't matter whether the anemia is a microcytic anemia, macrocytic anemia, normocytic anemia, megaloblastic anemia. It doesn't matter. When the person is having anemia, the patient is going to have say, in this. Okay? That's okay. Yes. So, sorry for the technical glitch, guys. Sorry for the technical glitch. What exactly I'm discussing about here is about these anemias. Okay? So, the anemia in males is less than 13.5 grams of hemoglobin per deciliter. Anemia in females is less than 12.5 grams per deciliter. Okay? So, anemia in males and females. If a patient is having anemia, the patient is going to have hypoxic symptoms. That's what I have discussed. Okay? So, what are the hypoxic symptoms? I have given here. The patient is easily getting tired. Female is going to say, "So, I'm getting tired very easily." Okay? These are the things. Now, how many types of anemia are there? See, based on the RBC size, the size of the RBCs, okay, the size of the RBCs. See, the size of the RBCs is not normally measured in femtoliters. The size of the RBC is measured in femtoliters. The volume of the RBC is measured in femtoliters. So, the usual size of the RBC is 80 to 100 femtoliters. Okay? Usual size. That's the usual size of the normal RBCs. If the RBC size, if the RBC volume, I should say, the RBC volume, if it is less than 80 femtoliters, okay, if it's less than 80 femtoliters, which means the RBCs are bigger being smaller. Now, these are the smaller RBCs. So, now when the RBCs are smaller, then those kind of anemias are called as microcytic anemias. Microcytic anemias. Okay? They are called as microcytic anemias. So, RBC size if it is less than 80 femtoliters, microcytic, short RBCs, small RBCs. Okay? Now, if the RBC size today is greater than 100 femtoliters, okay, big size RBCs. Now, the humongous RBCs. So, the anemias in which the size of the RBCs is increasing. So, such kind of anemias are going to be called as macrocytic anemias. Anemias. And there are anemias where the size is normal, sir, 80 to 100 femtoliters. Okay? There are anemias where the size of the RBCs is in a quite normal range. So, such kind of anemias are called as normocytic anemias. You can almost. So, anemias are of how many types? There are three types of anemias. What are they? Microcytic anemias, macrocytic anemias, and normocytic anemias. Okay? Micro, macro, normo. So, based on what? Based on the volume, based on the volume of the RBCs. Big RBCs, smaller RBCs, or normal-sized RBCs. Now, without any further aid, now let's begin our first topic, that's a microcytic anemias. The microcytic anemias. What exactly are these microcytic anemias? In the name itself, it's a microcytic, means small RBCs, small RBCs, that is less than 80 femtoliters. Less than 80 femtoliters. Okay? 80, not 8, 8500 liters. Okay? Now, my question is, why small RBCs? Why is small RBC? Okay? Why small? Okay? Why small size RBC? For example, let's put it this way, sir. Okay? Let's put it this way. Now, imagine there are 10 people in your family. There are 10 people. You need a bigger home. If there are only two people, you need a small home. That's a basic logic, right? In the same way, when do you need a normal-sized RBC? When the normal amount of hemoglobin is there, normal volume of RBC. If the amount of hemoglobin is going down, okay, the amount of hemoglobin is going down, the hemoglobin is getting down, sir. So, less amount of hemoglobin, less amount of hemoglobin production. Wireless amount of hemoglobin production, I will tell you. Okay, sir. Now, less amount of hemoglobin is there, sir. So, because of less amount of hemoglobin, RBC size also smaller. So, that's why microcytic. Now, as there is less amount of hemoglobin, what do you think RBCs are going to be good red in color? Are they going to become pale color? So, RBC hemoglobin production is decreasing. So, the RBCs are going to look pale color. So, hypochromic curves are same. Hypochromic, chromic means color. Hypochromic RBCs. That's a pale RBCs. Pale. Okay? So, hypochromic microcytic. Hypochromic microcytic. Microcytic corpuscles are going to be seen in microcytic anemias. Now, question is, why less hemoglobin? Why hemoglobin is less? Hemoglobin is less because you should understand first of all, what is hemoglobin? So, first of all, see, it's what is hemoglobin? The hemoglobin, it's a protein. It's a pigmented protein made up of heme plus globin. Okay? So, simple. Okay? Which is made up of globin. Globin is made up of alpha globin chains and beta globin chains. Alpha globin, beta globin chains. So, then what is this heme? The heme is made up of two things. Heme is made up of iron and protoporphyrin. Iron and protoporphyrin. Okay? Now, say, you need to understand why microcytic anemias. Why microcytic anemias? Maybe one reason is iron deficiency. So, when iron is deficient, okay, when iron is deficient, heme synthesis is not going to be there. Without heme, hemoglobin production goes down. Simple. Second thing, sir, protoporphyrin production. The protoporphyrin ring, there is a protoporphyrin ring. Okay? So, there is a big pathway for the production of this protoporphyrin. If this protoporphyrin is not getting produced, again, heme is not going to be there. Without heme, no hemoglobin. Okay? So, you can have iron deficiency anemia, possible. You can have defect in the production of the protoporphyrin. So, without product, iron, where iron will go? Iron is not going to bind with anything. Iron is simply staying within the cells. That will cause sideroblastic anemias. Okay? So, protoporphyrin deficiency will cause sideroblastic anemia. Iron deficiency will cause iron deficiency anemia. And, sir, globin chains, the globin alpha globin and beta globin chains are not there. Okay? Insufficient, not sufficient. So, the globin protein is not getting produced. So, the globin protein is not getting produced. Again, without globin, there is no hemoglobin. So, that will cause what? Thalassemia. That is the defect with the globin chains. Okay? Where there is no, not enough globin. Where there is not enough globin. Okay? So, these are the different causes of decreased hemoglobin production. Without hemoglobin, or with a little amount of hemoglobin, small, small RBCs. That's a microcytic RBCs. Okay? As simple as that. So, without any further lead, now let's begin our topic, microcytic anemias, or the causes of microcytic anemias. There are four important causes of microcytic anemias. Okay? Four conditions. In four conditions, you will see microcytic anemias. What are the four conditions in which you will see microcytic RBCs, small, small RBCs? One is iron deficiency anemia. Iron deficiency anemia. Okay? Where iron is not there. Second one is sideroblastic anemia. Sideroblastic anemia. Causes of sideroblastic anemia. It's a protoporphyrin is not there, not available. Next, third one is thalassemia. Thalassemia. So, in thalassemia, there is a problem. It's a globin, okay, deficiency of the globin chains. And one more condition is there, which is called as, I will explain you, anemia of chronic disease. Anemia of chronic disease is something seen in the patients who are hospitalized. Okay? The patients who are having chronic infections or chronic inflammatory conditions. In those people, you will see the anemia of chronic disease. I will explain you, don't worry. So, without any further late, now let's begin our topic with iron deficiency anemia. Okay? So, first microcytic anemia that I am talking here is iron deficiency anemia. So, iron is not there. Okay? Iron deficiency anemia. Now, iron deficiency is the most common nutritional disorder. Okay? The most common nutritional disorder, sir. Now, the point which I want you to know is, why a patient can get iron deficient? Okay? Why a patient can get iron deficient? So, before I am telling you, before before telling you why a patient gets iron deficient, let me tell you some important points about the basic iron absorption. Okay? Basic iron absorption. So, there are two forms of iron. Two forms. Okay? There are two forms of iron. One is ferric iron and ferrous iron. Ferric iron and ferrous iron. The ferric iron, you will get it especially from the plant sources. And ferrous iron, you will get it from animal sources. Okay? So, animal sources will give you a ferrous form of iron, that is Fe2+. And from the plant sources, you will get Fe3+ form of iron. See, this ferrous iron, okay, this ferrous iron, this is readily absorbed. Readily absorbed. You can easily absorb it. You can easily absorb it. But if Fe3+ form of iron is not absorbed, it's not absorbed. It's not absorbed. Okay? So, who is going to have a problem? Vegetarians or non-vegetarians? So, it looks like the non-vegetarians. It looks like the vegetarians are going to have the problem because they are getting Fe3+ form of iron, and this Fe3+ form of iron is not going to be absorbed. But in reality, there's not going to be any problem. There's no problem, sir, because you should understand, say, this Fe3+ form of iron will be converted into Fe2+ form of iron. The Fe3+ ferric form of iron is converted into ferrous form of iron with the help of what? With the help of acid in the stomach. So, the acid in the stomach converts ferric iron to the ferrous iron. Okay? Even so, vegetarians, if they take Fe3+ form of iron, that will be converted into Fe2+ form of iron. So, now, this Fe2+ form of iron, now this is in the duodenum. Okay? Now, imagine this is the duodenum. Now, here we have Fe2+ form of iron. Now, this Fe2+ form of iron needs to be absorbed. So, this is the duodenal. Okay? Now, this is the duodenal enterocyte. Now, on this duodenal enterocyte, there is a transporter present. Okay? There is a transporter present, sir. This is a transporter. It is called as DMT1. Okay? DMT1. So, with the help of this DMT1 transporter, iron is coming into the cell. So, name of this transporter is DMT1, divalent metal ion transporter one. With the help of the divalent metal ion transporter one, Fe2+ is coming into the cell. Now, from the cell, now the iron has to come into the blood. Okay? It has to come into the blood. We don't want the iron in the cells. We don't want the iron in the enterocytes. The iron has to come into the blood. From the blood, iron has to go to the bone marrow for the production of hemoglobin. So, iron has to go to the liver, where is the storage site? So, this iron, see, now it is coming out of the cell. It is coming out again with the help of one more transporter protein. So, this transporter protein that I am highlighting here, this is called as ferroportin. So, with the help of the ferroportin, iron, Fe2+, it is coming out. So, it is coming out, sir. But in the way, okay, the Fe2+ form of iron will be again converted back to Fe3+ form of iron. Okay? With the help of something called as hephaestin. There is something called as hephaestin, which will convert Fe2+ form of iron into Fe3+ form of iron on the surface. There is something going to be hephaestin, which converts Fe2+ to Fe3+ back again. So, now, this Fe3+ form of iron is coming to enter into the. Now, this iron is just like a naughty boy. Okay? He's just like a naughty boy. Or naughty boys will do naughty things. They will go after all the girls. Okay? So, this Fe3+, this is also a free radical. It's a free radical. As it's a free radical, it will react with the water, and it will form, and like, you know, there is something called as a Fenton reaction. It generates free radicals, and these free radicals will react with the cell membranes, causes the damage. So, we are not supposed to, we are not supposed to leave this iron in the free form. So, this iron needs to be bound. Okay? You need to capture this iron, sir. Actually, because iron needs to be captured. So, who is capturing it? It's a plasma protein. What is the name of this plasma protein? This plasma protein to which the iron is bound, it is called as transferrin. Now, this transferrin, it transfers the iron to the bone marrow. Okay? It's giving the iron to the bone marrow. Okay? This is bone. Iron is coming here to the bone marrow. In the bone marrow, in the bone marrow macrophages, the iron is going to be stored. The iron is going to be stored in the bone marrow macrophages. And where else the iron will go? The iron will also come to the liver cell. Okay? So, where the iron is getting stored? So, where the iron is getting stored? So, iron is getting stored in the bone marrow and iron is also getting stored in the liver. So, in the bone marrow as well as the liver, the iron is getting stored. Now, in which form? In a free Fe3+ form. So, this iron which is stored in the body, this iron stores are called as ferritin. Okay? The iron stores are called as ferritin. Okay? So, these are the points which I want you to know regarding normal absorption of the iron. Okay? Next, say, let me again tell you, the iron is coming into the blood with the help of the transporter called as ferroportin. Now, when the blood iron is bound with transferrin, transferrin transfers the iron to bone marrow macrophages as well as liver. What is the storage form of iron? Fe3+. The storage iron is called as ferritin. The storage is called as ferritin. Now, let me tell you why someone gets iron deficient. Okay? Iron deficiency. Why someone gets iron deficient? What might be the reason? So, I have already said you, iron deficiency is the most common nutritional disorder in the world. It's very easy that one can get into iron deficiency. Iron deficiency can be seen in adults, especially with the peptic ulcer disease. Peptic ulcer disease. So, peptic ulcer disease means these ulcers will bleed. The ulcers are going to bleed. The bleeding will come out in the form of hematemesis or either melena. Okay? The peptic ulcer disease can cause. Second cause of iron deficiency can be seen in infants. Infants who are breastfeeding. So, in infants who are breastfeeding, so the milk is deficient in iron. The milk is deficient in iron. So, the infants who are totally exclusively breastfeeding, they might end up in iron deficiency. Biblical. So, disease is one reason. Or the patient who is having colon cancer. Okay? Colon cancer or polyps in the colon, which can lead to bleeding. So, colon cancer. So, these cancers, they will bleed. Or polyps, polyps, especially the rectal polyps. Okay? Juvenile rectal polyposis, they can bleed and they can lead to iron deficiency. So, bleeding means what? The person is bleeding. The person is bleeding means the person is losing the iron. Why? Because bleeding means that he's losing the RBCs. He's losing the RBCs. He's simply losing the iron, sir, because in the RBC, hemoglobin is there. In the hemoglobin, iron is there. Okay? So, iron is going out of the body. So, any hemorrhagic condition, any hemorrhagic condition can lead to iron deficiency. And, um, certain parasites. Okay? Certain parasitic infections like Ancylostoma duodenale. Ancylostoma duodenale. And the name itself, it's a duodenale. It's going to live where? It's going to live in the duodenum. The duodenum is the site where iron absorption occurs. This is the iron absorption occurs. For example, here, if the parasite is living, means that parasite interferes with the iron absorption. Parasite is going to cause inflammation, so it interferes with the iron absorption. So, parasitic infections like Ancylostoma duodenale can lead to iron deficiency. So, breastfeeding in infants, um, the breastfeeding in infants. Or in adults, peptic ulcer disease. And in females, especially females are at a more risk of getting iron deficiency. So, females will get the anemia, right? Most of the time, females are going to have the anemia. I don't know why, sir. During menses, if they lose more blood, okay, that is menorrhagia. Okay? So, the patient is having menorrhagia, and there is excessive blood loss, that can also lead to iron deficiency. Okay? So, peptic ulcer disease, menorrhagia, breastfeeding, colon cancer, duodenal infections, all these are going to cause the iron deficiency in the person. And not only that, so if you use certain drugs like proton pump inhibitors. Okay? Let me add here, proton pump inhibitors. So, what are these proton pump inhibitors? Proton pump inhibitors like Omeprazole, okay, Pantoprazole. These drugs. Okay? Okay. So, so, proton pump inhibitors, what they will do? They decrease the acid production. Okay? They decrease the acid production. So, acid is the one important thing which helps in conversion of Fe3+ to Fe2+. Fe3+ to Fe2+. So, if you give proton pump inhibitors, acid is going down. When acid is going down, the conversion of Fe3+ to Fe2+ decreases. The conversion decreases. Now, Fe3+ is not getting converted into Fe2+. So, iron absorption decreases. And absorption decreases. So, proton pump inhibitors can cause iron deficiency. True. Okay? So, these are the points which I want you to know. And now, sir, okay? And anything else missing? Ah, next, what else can decrease acid? Gastrectomy. Gastrectomy. So, what exactly is gastrectomy? Gastrectomy means we have removed certain part. Certain part of the stomach we have removed. The stomach. A gastrectomy. Partial gastrectomy, complete gastrectomy, it doesn't matter. The patient, we have removed the stomach. If we decrease the, if we remove the stomach, what happens? The amount of acid that's getting produced is going to decrease. The amount of acid that's going to get produced is going to decrease. The conversion of Fe3+ into Fe2+ automatically decreases. Okay? So, automatically iron deficiency. So, these are the causes of iron deficiencies. Okay? Next, if the person is having iron deficiency, already I have explained you, sir, iron is not there. Without iron, can you produce heme? So, what is heme, sir? Heme is made up of iron, protoporphyrin. Now, iron is not there. Without iron, you cannot produce the heme. Heme is not there. Without heme, can you produce hemoglobin? No, sir. Hemoglobin production goes down. So, whenever you are having less hemoglobin, small size RBCs are enough. Garbage size will automatically decrease. So, that will cause microcytic anemias. Okay? That will cause microcytic hypochromic anemias. Microcytic hypochromic. Why in the name, hypochromic, you're right? Because the pale color RBCs. Now, how can we know that the patient is having iron deficiency anemia? So, female is going to come to the clinic and she's going to say, "So, I'm having the same symptoms, weakness, nausea, like lightheadedness, what I go, easy fatigability, all these things." She's going to say. If you look at the labs, okay, labs. Okay? So, when you look at the labs, what are the changes that are going to be seen? So, what about the ferritin levels? Iron deficiency. The iron deficiency, you know, so the stores of the iron, the bank, the iron bank, the ferritin. Okay? The store of the iron, ferritin levels automatically goes down. Okay? Ferritin levels automatically goes down. One thing. Second thing, what I want you to know is, what about the total iron binding capacity? Total iron binding capacity, TIBC. So, this TIBC, it's nothing but it's representing total iron binding capacity. Who will bind with iron, sir? Who will bind with iron? It is transferrin. Transferrin binds to the iron. So, TIBC. We are talking about here. I am talking about the ferritin levels. I am talking about the ferritin levels, sir. So, in my body, iron stores are going down. Okay? The iron stores are going down. So, what my body will try to do? My body will try to get more iron, somehow. My body will try to get more iron, sir. So, my body is increasing the number of carriers. Okay? My body, my liver is increasing the number of carriers. Uh, sorry, sorry, sir. This TIBC here, it represents transferrin. That's the main mistake. Okay? So, I'm talking about the transferrin, who is going to bind with the iron? It is the transferrin. Transferrin. Okay? So, transferrin, other carriers. So, whenever the, whenever the stores of iron, whenever the iron stores are going down, okay, whenever the iron stores are going down, body will try to get more iron by somehow. So, iron, a body is increasing the levels of transferrin molecules. More transferrins are there, so that at least more transferrins will bring more iron. If there is some amount of iron there in the GI tract, you can get it. Okay? So, remember always these two things go opposite. Whenever ferritin levels decrease, TIBC levels increase. Okay? Next, what else you should know, sir? So, these patients, ferritin levels increase, TIBC increases. What about the serum iron? In the serum, okay, iron in the blood, not in the stores. Serum iron, sir, it's just the iron deficiency. So, serum iron also goes down. So, iron number, the amount of iron which is present in the serum, serum iron also goes down. So, ferritin goes down, TIBC increases, serum iron decreases. Okay? These are the points which I want you to know. Apart from this, in the labs, what you can see is, sir, RDW. Okay? RDW, Red Cell Distribution Width. Okay? Red Cell Distribution Width is going to increase. So, what is this RDW and why it is increasing? The first, let me ask you, sir, iron stores are going to decrease gradually. Are they going to decrease suddenly at a time? Iron stores will come gradually down. Okay? Iron stores are going to decrease gradually. With time, one RBC can live up to 120 days, sir. Okay? One RBC can live up to 120 days. That is almost four months. Four months. So, initially, when iron is going down, RBC size is decreased. Within the next month, RBC size is little more decreased. In the third month, RBC size is little more decreased. So, if you look at the blood, okay, if you look at the blood smear, there are different sized RBCs. Different sized RBCs are going to be seen. So, Red Cell Distribution Width, the sizes of the RBCs are going to be greatly varied. So, that's why Red Cell Distribution Width is different sized RBCs. Rent sizes. Okay? Different sizes of RBCs are going to be seen. So, this is one thing. Next, what about the free protoporphyrin? What about the free protoporphyrin? Now, some students will get it out, sir, what is this free protoporphyrin? It's also evaluated. First of all, what is it and why it is getting elevated? Same, I have explained you that who is going to bind with the protoporphyrin, sir? The heme is nothing but, okay, heme, it is nothing but iron and protoporphyrin. Okay? Heme is nothing but the protoporphyrin ring in which the central iron is there. Okay? So, heme is a combo of iron and protoporphyrin. Now, in our condition, what about the iron, sir? Iron is deficient. Iron, iron is not there. When iron is not there, what about the protoporphyrin? Protoporphyrin is freely available within the cells. So, free protoporphyrin levels in the cell increases. The levels of free protoporphyrin levels are going to increase. So, that's why in iron deficiency anemia, the patients are going to have decreased ferritin, TIBC levels increases, serum iron levels decreases, Red Cell Distribution Width, and free protoporphyrin levels are going to increase, increase. Now, one more parameter which I want you to know, which the one more lab change that is a percentage saturation. Okay? So, what is this percentage saturation? What you have to know? Same, transferrin molecule. One transferrin molecule, for example, this is transferrin molecule. Okay? This is transferrin molecule, sir. Now, this transferrin molecule, okay, now it is binding with iron. So, it is binding with iron. Okay? It's binding with iron, sir. It can bind with many ions. Okay? It can bind with many ions, or almost it can bind with six irons. But it is not binding with all the irons. Okay? It can bind with all the iron, but it is not binding. Usually, the percentage saturation is going to be somewhere around 33%. Okay? The percentage saturation is going to be 33%. Okay? In our conditions, in our condition, tell me, iron is there? Iron is not there. So, iron, iron is not there. Okay? Not enough iron is there. So, what happened to the percentage saturation? What happened to the saturation of the transferrin? What happened to the saturation of this transferrin, sir? Saturation goes down. So, percentage saturation decreases. Okay? Percentage saturation, it decreases. So, that's the one important point which I want you to know. Now, okay? These are the labs. Now, what is the treatment? So, before treatment, I have to tell you one more condition where there is iron deficiency. And one more condition where there is iron deficiency. So, there is a condition called as Plummer-Vinson syndrome. Very important for the exams, especially for the board exams and like, you know, the FMGE exam. The Plummer-Vinson syndrome. What is this Plummer-Vinson syndrome? Syndrome is also called as Patterson-Kelly syndrome. Is also called as Patterson-Kelly syndrome. In this Plummer-Vinson syndrome, the patient is going to have three features. Three features are going to come together. In Plummer-Vinson syndrome, why I am discussing syndrome here is because the Plummer-Vinson patients are going to have iron deficiency anemia. Anemia. So, iron deficiency anemia. What is one more cause? Plummer-Vinson syndrome. The iron deficiency anemia is going to be seen. That is microcytic anemias. Next, what is esophageal webs? Imagine, okay, this is the lumen of the esophagus. In the esophageal lumen, you are having a web structure. Okay? There is a web structure that is present. For example, something like this. A web. Webbed structure. Esophageal web is going to be present. And last one is angular cheilitis or atrophic glossitis can be seen. Okay? Atrophic glossitis. And angular cheilitis, the patient is going to have a large, red, beefy tongue. Okay? Large, red, beefy tongue is going to be seen. So, at the end of the day, the only point which I want you to know for your exams is the Plummer-Vinson syndrome. It is associated with iron deficiency. Okay? I associate with iron deficiency anemia. Okay? So, I have explained you here what are the causes. Any hemorrhage can lead to iron deficiency anemia. Okay? Next, what are the laboratory changes that are seen? I have explained you. So, what is the treatment that is done, sir? Is supplementation of the iron. Okay? Supplement iron supplementation. That is the ferrous sulfate tablets. The treatment is ferrous sulfate tablets. If you are sulfate tablets are given. The first type of microcytic anemia is completed. What's the first type? Iron deficiency anemia. So, after iron deficiency anemia, now let's discuss about the second type of anemia, sir. The second type of anemia that I am going to discuss is anemia of chronic disease. First, let us discuss about the anemia of chronic disease. Later, I will discuss about the other two, sideroblastic. Okay? So, now let's discuss about anemia of chronic disease. So, anemia of chronic disease. So, if there is any chronic condition, chronic condition. So, the patient is having some chronic condition, for example, like autoimmune disorder. Okay? Autoimmune disorder or any chronic infection. Okay? The patient is having chronic infections. Okay? Usually more than six months. The chronic infections, chronic autoimmune disorders, or the patient is having cancers. Patient is having cancers. Now, in all these, all these are the examples of chronic diseases. Okay? Now, in all these chronic conditions, okay, and one more thing, usually the question is going to come something like the patient is usually hospitalized. Okay? In the hospitalized patients, like, you know, the chronic patients. Okay? So, hospitalized patients. Hospitalized patients. So, in these patients, you know, acute phase reactions are going to be produced. One acute phase reactant is going to be produced. Okay? By the liver. Whenever there is chronic inflammation in the body, you know, there is chronic inflammation in the body, the liver is going to produce a protein which is called as hepcidin. Hepcidin. Now, do you know what is this hepcidin going to do? So, hepcidin is always against iron. It's always against iron, sir. What it will do is, it decreases the iron levels in the body. Okay? Decreases iron levels or I should say, it decreases the iron absorption. Okay? Decreases iron absorption. And all the iron whatever is there in the blood, okay, all the iron whatever is there in the blood, that will be packed inside the bone marrow and will be packed inside the liver. So, now iron is not freely available anywhere. Why it is happening? Because the iron is one of the most important substance for the bacteria, for the bacterial growth. Iron. So, our body is thinking something like, sir, there is some infection going on in the body, so we should not give the food for the bacteria. The iron is acting like a food, sir. It's very important for the bacterial, like, you know, growth. So, all the iron is packed inside the bone marrow or the liver. So, now iron is not there outside anywhere. Anywhere iron is not available, sir. Iron is there in the body, but it is not available for hemoglobin synthesis because iron is totally packed within the liver. Iron is not coming out. Iron is not available for the synthesis of hemoglobin. Okay? So, iron levels. So, this is the anemia of chronic disease. So, anemia is going to be seen in patients who are having chronic diseases or chronic inflammations. Okay? So, if you look at the labs, okay, if you look at the labs, so how the labs are going to be? What about the ferritin? So, is this any deficiency of iron? If there is any deficiency of iron? No, sir. Even ferritin levels actually increases because all the iron whatever is in the serum, all the iron whatever is freely there, all the iron is now packed inside the liver and bone marrow. So, ferritin levels are going to be more. That if more ferritin is there, means already you are having more ferritin, sir. So, what happened to TIBC? That is transferrin levels. The carrier molecules. You are having sufficient amount of iron. When you are having sufficient amount of iron, what happened to the TIBC? The TIBC goes down. Simple. Transferrin molecules level goes down, right? Now, you don't want any carrier molecules. You don't want iron. So, TIBC is going down. Next, what happened to serum iron? It's a serum iron. I have said you, all the iron is going to be packed. So, serum iron also decreases. What happened to percentage saturation? The percentage saturation also decreases. Everything decreases. Okay? Percentage saturation is also going to decrease. Okay? So, this is the point which I want you to know. It's a culprit here. The culprit is hepcidin. Okay? In anemia of chronic disease, chronic inflammatory conditions, cancers, autoimmune conditions, liver is going to produce a molecule which is called as hepcidin. Hepcidin inhibits iron absorption. Inhibits iron absorption through also hepcidin inhibits erythropoiesis. Erythropoietin production, EPO production. Okay? So, no erythropoiesis, no hemoglobin synthesis. That can lead to anemia of chronic disease. Okay? That can lead to anemia of chronic disease. So, in this condition, what happened to ferritin levels? Ferritin levels are going to be more. TIBC levels are going to be less. Serum iron is going to be less. Percentage saturation is going to be less. Okay? What about the free erythrocyte protoporphyrin? Erythrocyte free protoporphyrin levels. Again, in this condition also, see, iron is not available. So, iron is not available for hematopoiesis or for hemoglobin synthesis. Iron is not available. So, when iron is not available, tell me, what happens? If iron is not there, okay, iron is not there, so protoporphyrin is going to be free. Okay? Protoporphyrin levels within the cells are going to be more. More than completed. Okay? Next, what else I have to teach you is, if you look at the RBCs under the microscope, what you will see, sir? This anemia of chronic disease, you have taught anemia of chronic disease under microcytic anemias. Microcytic anemias. So, RBC size is going to be less, right? RBC size should be less than 80 femtoliters. But most of the time, say, RBC size will be normal. The RBC size is normal. So, anemia of chronic disease, yes, of course, we are discussing it under microcytic anemias, but you look at the size of the RBCs, they are normal. So, they are normocytic. Okay? Normocytic anemias. So, tell me, if they ask you anemia of chronic disease, is it a microcytic anemia or normocytic anemia? The best answer is going to be a normocytic anemia. Though, yes, I know I have discussed it under microcytic anemias, but most of the time the RBC size will be maintained normal. So, it's a better example under normocytic anemia. Okay? So, what's the treatment? You have to simply, like, you know, address the underlying cause. Just address the underlying cause. What is wrong with this patient? Okay? So, why the chronic inflammation is there? Why the chronic infection is there? Okay? What is that autoimmune disorder? You just try to address the problem. The second type of anemia is also completed, sir. Now, the third anemia that I'm going to start, third microcytic anemia that I'm going to start is sideroblastic anemia. Sideroblastic anemia. So, what is this sideroblast? Sidero means iron. Sideroblastic anemias. Say, in the sideroblastic anemia, what is the problem? So, decreased protoporphyrin. Decreased protoporphyrin, sir. Okay? So, when protoporphyrin is not there, say, protoporphyrin has to bind with the iron and forms heme. Now, protoporphyrin is not there, sir. What happened to the heme, sir? Heme also decreases. When heme is not there, so, when heme is not there, do you think hemoglobin will be there? No. Hemoglobin. No hemoglobin. So, if hemoglobin is not there, that causes microcytic anemia. Okay? MCA, microcytic anemia. Okay? Now, what I want you to know here is, the how the protoporphyrin is synthesized. Okay? How the protoporphyrin is synthesized? Let me show you the look here. These are the different stages in which the protoporphyrin is going to bind with the iron. The protoporphyrin is going to bind, take the iron and forms heme. Forms heme. Okay? Now, the most important point is, in the production of protoporphyrin, what do you need? Enzymes. Which enzymes? ALA synthase. Okay? ALA synthase. This is an enzyme. Aminolevulinic acid synthase. Okay? Synthesis. This enzyme is required. And ALA dehydratase. Okay? ALA dehydratase. Okay? This is ALA, AS, AS, ALA, AD, ALA. So, this ALA and ALA, these are the enzymes which are very much important in the production of protoporphyrin. So, if these enzymes are deficient, the enzymes are deficiency, or these enzymes are inhibited, these enzymes are not functioning, at the end of the day, protoporphyrin is not going to be produced. If protoporphyrin is not produced, no heme. Iron is going to be free within the cells. Iron is freely present within the RBC, right? And it's freely present within the cells. Iron causes damage to this. Simple. So, iron is accumulating within the cell. Iron is accumulating within the cell. So, this iron-loaded cell is called as sideroblast. Sideroblast. So, let's write one by one. What are the problems that, what is the problem that is seen in the sideroblastic anemia? Let me write here, sir. Same, sideroblastic anemia. This aminolevulinic acid synthase, that is ALA. This enzyme, ALA and ALA dehydratase. These are the most important enzymes in the production of the protoporphyrin. Protoporphyrin. And one more enzyme is there, which is called as ferrochelatase. So, where is the ferrochelatase? We haven't seen these ferrochelatase. Now, just wait. Look here. So, the last step there. Okay? The last step. The ferrochelatase is the one which helps in binding iron and protoporphyrin. Iron and protoporphyrin, they will fuse and form heme. Form heme. So, if this ferrochelatase, again, if it is also defective, that will also cause, that will also cause sideroblastic anemia. Free iron is going to be there. That will cause sideroblastic anemia. So, let's write one by one. Say, why these enzymes are important? Let me tell you, sir. In most of the cases, there is deficiency of this enzyme, ALA synthase. Deficiency by birth itself. Congenital. Congenital deficiency of ALA synthase. Okay? What else, sir? Lead poisoning. There is something called as lead poisoning. The lead poisoning, alcoholism. The lead poisoning, alcoholism, they will cause. Okay? They will cause deficiency of this enzyme. Okay? Lead poisoning. If lead poisoning is there, ALA dehydratase is going to be affected. Congenital deficiency of ALA synthase can be seen. And for the functioning of this aminolevulinic acid synthase, for the functioning of this aminolevulinic acid synthase, what do you require? You require vitamin B6. Pyridoxine is required. So, if the B6 is deficient, if the B6 is deficient, this enzyme is not going to function. That enzyme is not going to function. If that enzyme is not functioning, protoporphyrin is not produced. If protoporphyrin is not there, heme is not there. Without heme, no hemoglobin. So, that will cause microcytic anemias. So, what are the causes of the sideroblastic anemia? The causes of sideroblastic anemia are B6 deficiency. B6 deficiency can cause it. Lead poisoning can cause it. Alcoholism can cause it. Okay? So, these are the important causes. Important causes are B6 deficiency, lead poisoning, and alcoholism. They will also cause and they will also affect ferrochelatase. Sorry, excuse me, sir. So, now, in this condition, sideroblastic anemia, tell me, what happens? Protoporphyrin is not there. Why protoporphyrin is not there? These enzymes are deficient. They are stopped functioning. Okay? Now, if this protoporphyrin is not there, what happened to the iron? Iron is freely available. More iron, more iron is getting accumulated within the RBC. So, those iron-loaded RBCs are called as ringed sideroblasts. Okay? This is so, this is actually RBC. Okay? Now, in the RBC, you see there is an iron accumulation. There is iron accumulation. Okay? So, this is an actual immature cell. Okay? Immature cell. The patient is having severe anemia. The patient is having anemia so that the immature cells are coming into the circulation, like mature cells are coming into the circulation, sir. Normally, within the RBC, are within the RBC, are not supposed to see any nucleus. You are not supposed to see any nucleus. So, now, these are the nucleated RBCs. These are the nucleated RBCs. The nucleated RBCs are coming into the peripheral, like, you know, stream, because the patient is having severe anemia. So, in order to counteract that anemia, the immature RBCs are coming into the blood. That too, these immature RBCs, they are loaded with iron. Lots and lots of iron is there. Freely available in the cytoplasm. Why the iron is freely available? Because protoporphyrin is not there. No one is accepting the iron. Okay? No one is accepting the iron, sir. So, iron is freely available. So, I have said your iron is a free radical. What iron will do? Iron will cause damage to the cells. Iron will cause damage to the RBCs. RBC lysis. Most of the immature RBCs, and again, upon which the RBCs are going to be destroyed. So, the RBCs are destroyed. What happened to all this iron? Iron will leak into the blood. Iron is now freely leaking into the blood. So, this iron is causing the damage to the RBCs. So, it is damage to the RBCs will cause the leak of iron into the blood. So, iron levels in the blood increases. So, let's write one by one. So, what are seen in the labs in sideroblastic anemia? What is seen in the labs? The labs may. What about the ferritin levels? The ferritin levels are going to be more. What is ferritin, sir? Iron. Iron is more available. Is not there? So, much iron is freely there. No one is using the iron. Freely available iron. So, ferritin levels increases. So, when you have more amount of iron, do you need any further absorption? No. What happened to the transferrin? The transferrin, the carrier molecules, goes down. You already have iron. So, transferrin goes down. Okay? Next, what about the TIBC? Or let me first say, what about the serum iron? What about the serum iron, sir? The RBCs are dying. So, the dying RBCs, the immature RBCs are dying, sir. So, from this immature RBCs, iron is going to leak into the blood. Iron is going to leak into the blood. So, more iron is going to be there in the serum. So, serum iron levels are going to be elevated. So, the serum iron levels are going to be elevated. If more serum iron is there, what happened to the percentage saturation? Percentage saturation also increases. Percentage saturation increases. More iron is there in the blood. Okay? So, this iron will go on bind with the transferrin. Okay? Whatever the transferrin are there. Of course, transferrin levels decreases. So, whatever the transferrin are there, the iron will go and bind with the transferrin. So, percentage saturation decreases. Sorry, increases. A percentage saturation increases. So, this is how the laboratory values are going to be changed in a patient who is having iron deficiency, sideroblastic anemia. So, sideroblastic anemia are some important causes. B6 deficiency. B6 deficiency. Because B6 is the cofactor, sir. B6 is the cofactor for the production of this enzyme here. If you want to have this ALA synthase activity, if you want to, if you want the ALA synthase to function normally, you need require B6. So, B6 is the cofactor for the enzyme. If this B6 is not there, this enzyme won't function. If that enzyme is not functioning, protoporphyrin is not there. Without protoporphyrin, no heme. Without heme, no hemoglobin. Microcytic anemias. Microcytic anemias. Okay? B6 deficiency can cause sideroblastic anemia. Okay? Alcoholism, lead poisoning. Okay? Okay, alcoholism, lead poisoning. They inhibit the ALA dehydratase. Okay? This one, sir. ALA dehydratase. Alcoholism and lead poisoning will also inhibit the ferrochelatase. At the end of the day, protoporphyrin is not there. Without protoporphyrin, free iron. Free iron means sideroblastic anemia. In one of the exams, this question was asked, sir. Especially in the Indian exam, this question was asked, sir. Say, what is the stain that is used? What is the stain that is used? The stain that is used here is Prussian blue.

Blue stain, okay. Because the stain that is used for the iron A's Pearl stain, Pearl stain, are Prussian Blue stain. Cold stain, okay. Pearl stain are Prussian Blue stain is used for containing the iron. So this other blast, okay. So done bottles, I should teach you this is cytoplastic anemia. Can be seen. Let me put it this way. So cytoplastic anemia can be seen in a patient who is having B6 deficiency. Just now I have explained the basics deficiency because when B6 is not there, amortic acid synthase is not functioning in the seminal 11 acid synthesis. If it is not functioning, you're right. So that's why the patient is getting basic deficiency. Why the patient is getting V6 deficiency is because the patient is using anti-tubercular medication. What is that anti-tubercular medication? Isoniazid. So the size warrior said causes Basics deficiency. The person who is using isoniazid can become Basics deficient. The basics deficient, the paradoxin, the basics paradox in the paradoxin deficiency can lead to non-functional graphics enzyme, amino levelic acid synthase enzyme is not going to function without the B6, without that cofactor. So that can lead to ceroblastic anemia. No protoporophy in central plastic anemia. Okay. So the third type of anemia is also completed. Okay. Ceteroblastic anemia is also completed, sir. Okay. Next, uh, fourth type of microcytic anemia that I'm going to discuss here. The fourth type. So the fourth type is thalassemia. It's a thalassemiosum. Okay. So the thalassemia is the most common. Okay. The thalassemia is the most common hemoglobinopathy in the world. It's a hemoglobin related problem. Thalassemia is a hemoglobin ability problem. So do you know what is the problem with the thalassemia, sir? In thalassemia, the problem is efficiency, deficiency of the globin chains. Okay. Yeah, the patient is having anemia. Why anemia? Because deficiency of globins. Globin is deficient. That's it. Not a defective. It's not defective hemoglobin. Deficiency of the globin chains. Now, tell me, tell me, how many types of globulins are there? How many types of globin joints are there, sir? Alpha globins, Beta globins. If Alpha globin chains are defective, not defective, sorry. If Alpha globin chains are deficient, if Alpha globin chains are diffusion, that will cause Alpha Thal. Okay. Alpha thalassemia. If the beta globin chains are defective, ah, sorry, not effective. Deficiency. The beta globin chains are deficient. If the beta Global protein is deficient, that will cause beta thalassemia. Alpha thalassemia or beta calcium. So how many types of calcium are there? Alpha and beta. If Alpha chains are deficient, Alpha cell sim. Has a beta sins are deficient, beta calcium. Okay. Actually, normally you have two alpha chains, two beta chains, two alpha genes, and two beta chains will be there. Efficiency of alpha genesis, beta thalassemia. Okay. So, so why thalassemia? What is the problem with the calcium, sir? It's a hemoglobinopathy. The hemoglobin related problems are the most common hemoglobinopathy. What is the hemoglobin related problem? Globin chains are deficient. Roman chains are deficient. First, let's discuss about the alpha thalassemia. Okay. Same in alpha thalassemia, the points which I want you to know is, sir, actually there are four Alpha Genesis. Okay. The alpha, the alpha globins, right? Okay. Alpha globin chains are deficiency, right? First, Alpha calcium. Alpha globin chains are deficient. So quantitative problem, not the quality. Quantity is lesser. Quantitative problem. So Alpha globin chains are deficient. See, for this Alpha globin, globin is a protein that should be genes. So how many genes are there? How many Alpha genes are there? There are four Alpha genes. There are four Alpha genes. Alpha genes are four, sir. Alpha genes are four. Alpha genes are there. Okay. So these Alpha genes are present on chromosome number 16. Okay. They are present on the chromosome number 16. Or Alpha genes. Before going further, I want you to know one more important point. I want you to know one more important point. Normally, we adults, maybe adults, we have which type of hemoglobin? HBA. Okay. HBA also HBA2. There is one more type of hemoglobin called as HBA2. And fetus, fetus. During intra, like in the fetal period, fetus is going to have fetal hemoglobin, HBF. So what is the difference between HBA, HBA2, and HBF? What is the difference between different types of hemoglobin? So adult hemoglobin is made up of two alpha chains, two beta chains. Just now I have discussed you know it. So there are two alpha chains and two beta genes, two types of globins, alpha globins, beta globulins. Two alpha globes, two beta globids in HVA2, two alpha chains are there, and two delta chains are there. Two alpha, two delta. Two alpha, two delta. In HBA2, it's all startled hemoglobin. HV A2. In HBF, fetal hemoglobin. So Alpha2, Gamma2, sir. Alpha2 and Gamma2. Different type of like, you know, people in adults and in children. Now here, the point is, sir, what is alpha thalassemia and why it is coming? Alpha thalassemia is due to deficiency of the alpha globin chains. How many genes are there for the alpha globins? So there are four genes for the alpha groupins. There are four Alpha genes for Alpha genes. Now, same, sir, if one alpha Gene is deleted, deletion, sir, usually Alpha calcium is because of the gene deletions. In deletions, genes are deleted. If one alpha Gene is deleted, do you think will there be any problem? So no problems, asymptomatic. Asymptomatic. So the patient is usually asymptomatic. Okay. One alpha Gene is defective. The patient is going to be absolutely asymptomatic. So if two genes are deleted, two genes are deleted, two alpha genes are deleted, two alpha genes are deleted. Now Alpha globin chain production decreases. The alpha globin chain production decreases. If the alpha globin chain production decreases, mild anemia, child. Yeah, a little anemia, mild anemia is going to be seen. Okay. So if three genes are deleted, three genes are deleted, what happens? Now Alpha globin chains are not getting produced. Okay. Now Alpha globin chains are not going to be produced. If Alpha globin chains are not getting to be produced, who is what's the only change that is left over? Beta chains. Beta chains are there. There is no problem with the beta sheets. Now normally, Alpha chains and beta chains will be together. Alpha chains went with the beta chains. Okay. Alpha and beta chains are going to be together. Same. Now when Alpha chains are not getting produced because of the three genes are deleted, so Alpha Gene production, the alpha global production is going to be very much deficient. Now it's only beta genes and beta glomins are there. Only beta globulins are there. Okay. Beta globulins are there. Now only beta glomins are going to be defined with the beta globulins. So this forms beta globulins. So now, if three genes are deleted, that forms beta chains. The beta chains are going to form tetramers. Okay. Beta chains, only beta signs are there. Now it should be two alpha, two beta. Deter one, two alpha, two beta. Now only beta are there. So that causes beta chain tetramus. Okay. All are beta jets. Beta, beta, beta, beta. Now four beta chains. So this type of hemoglobin where beta atomers are seen, this type of hemoglobin where beta determines are seen, this is called as HPH. What is HBH? So HBH is nothing but so the patient is having deletion of three genes where there is severe anemia. The patient is having which type of hemoglobin? HPH means tetramars of beta there. Okay. So now this HBH, this type of hemoglobin, this type of hemoglobin is going to cause damage. It's going to cause damage to RBC. So RBCs are going to be undergoing lysis. When autolysis, that causes anemia. If four genes are deleted, see, four Alpha genes are deleted, four genes are deleted. If four genes are related, tell me. So there is no Alpha globin chain at all from the birth itself, or I should say in neutral itself. So the baby is not having any Alpha genes. All Alpha genes are deleted. All Alpha genes are deleted. The baby cannot produce any Alpha globin chains, sir. During intrauterine life, what type of hemoglobin is there? Hemoglobin F is there. Hemoglobin F also see it have two alpha Robin chains. Now, do you think the baby is going to produce this Alpha globin chains? No, sir. Alpha globin chains are not going to be produced. If Alpha globin chains are not produced, means only gamma chains are there. So only gamma, only gamma genes are going to be there in neutral life. So these gamma chains are going to form tetramus. These gamma chains are going to form tetramercial. So if four Alpha genes are deleted, means right tradition of four genes will cause gamma tetramers. These are called as hemoglobin Parts. This is called as this type of hemoglobin is called as hemoglobin Parts. So this is not compatible with lifestyle. The baby is going to die in uteroids. The baby is going to die in iterate cells. That's called as a Hydrops Fatalis. The Hydrops fatality. So the baby is going to die with severe anemia, severe anemia. So hydrops fetalis. Okay. So one alpha Gene deletion, not a problem. Two alpha Gene duration, mild anemia. Three Alpha gen mutation, or I should say that three Alpha Gene deletions, the three Alpha Generations can cause HBH. And four Alpha Gene deletions is not compatible with life. That is death in neutral because of High Drops if it are less. Okay. Hydrops fetalis. Okay. So alpha thalassemia is completed, sir. Alpha thalassemia is completed. Okay. Now after alpha thalassemia, what is the next variety? Beta thalassemia. Okay. What's the problem, sir? Actually, there are two genes per beta global. Okay. There are two genes for beta globinson. Okay. There are two genes per beta globals. Okay. Now when this genes are mutated, not deleted, mutated. Okay. When the genes are mutated, what happens? Gene mutation. A gene mutation. So there is efficiency again, not effective deficiency in beta globals. Gene mutations. Two types of genes are there. Two are not two types of it. Two pairs of two genes are the two genes where not two pairs also two genes are there. Two beta genes. Okay. So gene mutations can lead to efficiency of beta globulins. If beta globins are deficient, that causes beta thalassemia. Beta calcium. Now, let me put it this way, sir. These are the normal beta genes. Beta, beta. This is something normal. Two beta genes are functional. Both are functional cells. Okay. Now, what happens? Say, if the mutations are something like this, array. So it will be we are having how many beta genes? Two beta genes. One from the mother, one from the father. Okay. Now, one beta Gene is normal. One beta Gene got mutated. One beta Gene got mutated, sir. Now mutated means now it is going to produce this beta plus. What is this beta plus represent? It represents a beta plus. It represents um something like efficiency, deficiency of problem. Now it's going to yes, it's still working. It produces less beta globin. It codes for less beta globin. Now there is something called as beta naught. Beta naught. Made complete absence. It's not going to code for any protein. It's not going to code for any protein, sir. Zero production. Zero. It's not going to produce any protein. Okay. So the patient can have beta and beta not. Now, let's make it a little bit more problematic. Now, what if a patient is having both the beta genes? Beta, beta plus. Beta plus means both are mutated. Both are going to produce efficient globin chains. Now, let's make it more worser. More worse. The beta naught, beta naught. Means both complete options. They are not at all coding for. Okay. They are not at all coding for any weight available conditions. So how many combinations are possible? There are four combinations possible, sir. Say, let's take the extremes. Let's check out the extremes. So one is this one. One is normal. Other is little affected. Little affected. So this is called as minor beta Tal. Minor. A minor problem. Minor problem because one gene is normal. It's going for normal beta globins. And other region is little affected. So it is causing deficiency in the beta problems with a little deficiency in the beta globulins. And last one, sir, third, complete absence. Beta globes are not getting produced. Okay. This is more severe conditions. Sir, this is the more severe condition. This is the milder condition. See, beta cell minor is a minor condition. Beta cell measure is a it's a more severe condition. So this is called as beta thalassemia major. Okay. It's a severe condition. Okay. So now let's see about the beta thalassemia measure. Now, first, let's discuss about the beta cells minor. What is the problem? Is a problem is one is the normal. One beta globin Gene is absolutely normal. The other beta Globe engine is little affected. Little affected. So now, what are the symptoms, sir? The symptoms are going to be mild anemia. Okay. Mild anemia. Okay. Not a serious problem. While the patients are going to have mild anemia, sir, IA minor. See, now these patients. So these patients are going to have how to identify that the patient is? So this patient is, how can we say there's going to be essential changes in other types of hemoglobin? Okay. So what is that? Say, in beta calcium minor, the patient is going to have decrease HBA. Normal hemoglobin HBA. The HBA levels are going to reduce. And there is no doubt the HBO levels are going to decrease, slightly decrease, not much, slightly decrease. But the other types of hemoglobins are going to compensate. Lee, like, you know, they are going to rise as a compensate reaction. Okay. One type of hemoglobin is deficient, no? So other types of hemoglobin are going to rise. What happens in this condition is HBA2. HBA2 levels are going to rise. Okay. Argumentaries are almost getting double. So the normal levels of HBA2 is 2.5 percent. Normal HBA2 will be 2.5 percent. It becomes five percent. Okay. HBO2 levels will increase. Not only that, the HB F levels, the HBO F levels are also going to increase. F levels are also going to increase. So how to identify that the patient is having beta's ultimate minor? The patient is having mild animation. But when you do hemoglobin electrophoresis, okay, hemoglobin electrophoresis, you can see different types of hemoglobins. So the patient is going to have decreased HBA, but with increase HBA2 as well as HBF. Is the point which I want you to know. So usually these patients are not, uh, requiring any blood transfusions. They don't require any blade transfusion, sir. Usually they're carrying on, carrying on with their life. Okay. Normal, normal life. But what about the major, sir? Beta calcium major. Beta major. So this is more serious condition. These patients will die if you don't give blood Transmissions. They are surviving only on the surviving on blood transfusions. Okay. They're only surviving on the blood transfusions. So without blood transmission, they would like so every week or for every like, you know, uh, 10 days, they have to go and they have to take the blood transmission continuously. Okay. The point which I want you to know here is in beta calcium measure. So it's a more severe disease. Okay. See, if the beta genes are not there, the beta genes are not theirs, or no, or I should say the beta genes are mutated. Both the beta genes are mutated. So that is beta naught, beta naught. Beta genes are mutated. Then the beta genes are mutated. A beta globin chains are not going to be produced. Effective or I should say deficiency. Deficiency of the beta globin chains. When the beta globin chains are deficient, now beta globin is not there. Who is only there? Alpha globin is there. Alpha globin is there. So what happens? The alpha globin chains are going to fuse. Okay. Everywhere is Alpha globin. The four Alpha globin chains. So Alpha glucans form tetramars. Alpha chains form the drummers. Alpha genes will form the return. Okay. So this is the one point which I want you to now. So these Alpha chains are going to form tetramers and these Alpha tetramars are going to precipitate and they will cause the damage to the RBC. They will cause the damage to the RBCs. The RBCs are going to undergo extra vascular hemolysis. Okay. The RBCs are going to undergo extra vascular. Sometimes even intravascular hemolysis can occur. Okay. So this Alpha chains, they will precipitate and they will form. Okay. This Alpha chains, they will precipitate and cause damage. Because damage of the RBC, cause damage to the cell membrane of RBC. The RBC sentiment is going to be damaged because of this unpaired Alpha chains. Alpha chains. Okay. So because the damage to the RBC cell membrane. Okay. RBC cell membrane. So whenever the RBC is with the damaged cell membranes are seen in the spleen, the spleen is going to immediately destroy those RBCs. Are these are damaged RBCs? So let's just write. So extra luster hemolysis. The next important point with the beta thalassemia which I want you to know is, sir, the babies is not going to have any problem. Babies in the first six months, no symptoms, no symptoms. Why? Because, you know, the neutral also, no problem. In neutral also, no problem. Beta doesn't seem a major because in neutral, what kind of hemoglobin is there, sir? HBF hemoglobin is there. HBF hemoglobin is there. What is HBF? Alpha2, Gamma2. Alpha2, Gamma2. There is no such thing as beta. Okay. There is no such thing as beta chain. So beta calcium is the beta cells major babies when they are in neutral, they do not have any problem because there is no concept of beta. Okay. There is no point of the beta chain. So they're absolutely not one. But after taking birth, after taking birth, what happens? After the six months, the first six months also same. Fetal hemoglobin is dominant. So by six months, what happens? The by six months, the fetal hemoglobin is replaced with adult hemoglobin. Fetal hemoglobin is replaced with the adult hemoglobin. So fetal hemoglobin. But these babies do not have beta chains. These babies don't have beta chains. As they are not having beta chains, these babies are not having beta chains. Are only Alpha chains are there. Okay. So symptoms will start to appear after. The symptoms will start to appear after six months. First six months, that's arriving. After six months, they will be having problem. A problem. What's happening? The alpha chains will precipitate. Alpha chains will cause damage to the cell membrane. So damaged cells, that damaged RBCs are going to get broken down. Just plain. So that's the extra vascular hemolysis. That's going to occur. Extra vascular hemolysis are going to occur. So these patients are having very severe hemolysis because beta cellular patients are going to have very severe hemolysis. So lots and lots of hemolysis, suckling. So what my body will try to do? My body will try to compensate. My body will try to compensate. So how my body is compensating? Now, still now, the hemolysis, sorry, RBC production. Till now, the RBC production is happening in the bones, long bones in the body. Now, in order to produce more RBC, the hematopoietic activity will also start to occur in the flat bones or in the flat bones. Now, there is extra medullary hematopoiesis that's going to occur. So in this condition, beta calcium measure, there's going to be extra medullary hematopoiesis. Extramedullary hematopoiesis. Okay. So where hematopoiesis? Now, the hematopoiesis is happening even in the skull bones. Okay. Hematopoiesis is extended with scale bones. So that's why in these patients, okay, if you look at their face, okay, if you look at their face, so they face because of this extra Miller hematopoiesis, the thickness of the bones increases. Their face is going to look like a lion-like faces. Okay. Lion-like faces are going to be seen in beta calcium image. True. Okay. Lion-like faces are going to be seen. If you take an x-ray, see how the skull is going to look like. So all is spikes. They are representing extra medullary hematopoiesis. This is called as crew cut appearance. So crew cut appearance is seen on the x-ray. Reference is again next. What else? So more RBCs are getting destroyed, right? Because of the alpha chain precipitation. Alpha chains will cause the damage to the cell membrane. So whenever the damage cell membrane, damage cells are there, the cells are dying. The cells are dying. Usually RBC destruction happens in the spleen, but more cells are dying. So now this destruction of the cells are also happening in the spleen as well as the liver. So now they are doing more work. They are doing more work breaking down the RBCs. So the patients are going to have hepatosplenomegaly. So the patients who are having beta Thal major, okay, beta calcium measure, they are having yes, extravatory hematopoiesis, true. Because of that, they're going to have lion-like faces. Okay. Lion-like faces are chipmunk like faces. Okay. Chipmunk like faces or lion-like faces. A line like face is a chipmunk, chipmunk like faces. And one more thing on x-ray, what you will say? The crew cut appearance. Appearance is also called as hair on end appearance. Hair on end appearance can be seen on the x-rays. That's also possible. So more RBC breakdown is happening in the reticular endothelial system. So there will be hepatosplenomegaly. Hepato hepatomegaly and splenomegalism. Okay. So they can be hepatomegaly as well as splenomegalism. Now, if you do electrophoresis, HBO electrophoresis, what can be seen, sir? How to identify beta cell measure? This is the case of beta cell measure. Do you know what happens? So HB electrophoresis. So no HBA. Little to no HBSN. No HBA. No HBA. Hemoglobin A is made up of two alpha, two beta. Beta is not there. Beta is not there. That is not a hemoglobin A. So hemoglobin A is not there. Now what else is there, sir? So the patient is going to have HBA2 levels and HBF levels are elevated. So HBA2 and HBF levels are going to be elevated, sir. Okay. So definitely it's a micro set academia. Hemoglobin production is not there, sir. Hemoglobin production. The beta globin chains are not there. So less hemoglobin. So small size RBCs. So microstatic hypochromic armies are going to be seen. Especially in this condition, the patients are also going to have something like this. Let me show you. So this patients with beta thalassemia major, they will have this kind of Pharmacy, sir. So what are these Pharmacy? These are target cells. These are target cells. They are swimming like a blue eye, right? Bully or target, target cells. So why target cells? Because say the RBCs, first of all, that's more in size. What about the hemoglobin inside the RBCs? What about the hemoglobin amount of hemoglobin inside the RBCs? Now, less hemoglobin. Now, when there is less hemoglobin, now RBC membrane is not going to be stiff, sir. Let's put it this way, like, you know, in an easy way to understand. So now the hemoglobin is not going to be there. Deficiency of the hemoglobin. When less hemoglobin is there, now RBCs are going to become very loose. Hemoglobin is not there. They are not going to be stout. They are not going to be stiff. Now inside the cell, the hemoglobin is very less. So the membrane is going to be very much loose. So now the RBC membrane will become something like this. For example, say normal RBC membrane, it's like this, sir. So inside what is there? Hemoglobin. Good amount of hemoglobin is there. Good amount of hemoglobin is there. Okay. In the periphery, you are going to have more hemoglobins. Like this. But what happens in beta thalassemia? Thalassemia, there is severe deficiency of the hemoglobin. So RBC is going to become like in the membrane is going to become loose. So that loose membranes, the loose RBC membranes can form blephs like this. They can form what can form blips? Cytoplasmic are blephs. Okay. The cell membrane blips. Okay. They are forming the blips. Now, some amount of hemoglobin will come and get deposited over here. Some amount of hemoglobin. So yes, hemoglobin is there in the periphery. Okay. But the moment of hemoglobin will also come and get deposited in the center. So now the center also you can see that red color. So that's why, sir. Okay. So target cells can be seen. True cut appearance, the chipmunk faces or line like faces can be seen. Extra metal hematopoiesis. True. Because of that they're going to have lion-like faces. Okay. Lion-like faces are chipmunk like faces. Okay. Chipmunk like faces or lion-like faces. A line like face is a chipmunk, chipmunk like faces. And one more thing on x-ray, what you will say? The crew cut appearance. Appearance is also called as hair on end appearance. Hair on end appearance can be seen on the x-rays. That's also possible. So more RBC breakdown is happening in the reticular endothelial system. So there will be hepatosplenomegaly. Hepato hepatomegaly and splenomegalism. Okay. So they can be hepatomegaly as well as splenomegalism. Now, if you do electrophoresis, HBO electrophoresis, what can be seen, sir? How to identify beta cell measure? This is the case of beta cell measure. Do you know what happens? So HB electrophoresis. So no HBA. Little to no HBSN. No HBA. No HBA. Hemoglobin A is made up of two alpha, two beta. Beta is not there. Beta is not there. That is not a hemoglobin A. So hemoglobin A is not there. Now what else is there, sir? So the patient is going to have HBA2 levels and HBF levels are elevated. So HBA2 and HBF levels are going to be elevated, sir. Okay. So definitely it's a micro set academia. Hemoglobin production is not there, sir. Hemoglobin production. The beta globin chains are not there. So less hemoglobin. So small size RBCs. So microstatic hypochromic armies are going to be seen. Especially in this condition, the patients are also going to have something like this. Let me show you. So this patients with beta thalassemia major, they will have this kind of Pharmacy, sir. So what are these Pharmacy? These are target cells. These are target cells. They are swimming like a blue eye, right? Bully or target, target cells. So why target cells? Because say the RBCs, first of all, that's more in size. What about the hemoglobin inside the RBCs? What about the hemoglobin amount of hemoglobin inside the RBCs? Now, less hemoglobin. Now, when there is less hemoglobin, now RBC membrane is not going to be stiff, sir. Let's put it this way, like, you know, in an easy way to understand. So now the hemoglobin is not going to be there. Deficiency of the hemoglobin. When less hemoglobin is there, now RBCs are going to become very loose. Hemoglobin is not there. They are not going to be stout. They are not going to be stiff. Now inside the cell, the hemoglobin is very less. So the membrane is going to be very much loose. So now the RBC membrane will become something like this. For example, say normal RBC membrane, it's like this, sir. So inside what is there? Hemoglobin. Good amount of hemoglobin is there. Good amount of hemoglobin is there. Okay. In the periphery, you are going to have more hemoglobins. Like this. But what happens in beta thalassemia? Thalassemia, there is severe deficiency of the hemoglobin. So RBC is going to become like in the membrane is going to become loose. So that loose membranes, the loose RBC membranes can form blephs like this. They can form what can form blips? Cytoplasmic are blephs. Okay. The cell membrane blips. Okay. They are forming the blips. Now, some amount of hemoglobin will come and get deposited over here. Some amount of hemoglobin. So yes, hemoglobin is there in the periphery. Okay. But the moment of hemoglobin will also come and get deposited in the center. So now the center also you can see that red color. So that's why, sir. Okay. So target cells can be seen. True cut appearance, the chipmunk faces or line like faces can be seen. Extra medullary hematopoiesis. True. Because of that they're going to have lion-like faces. Okay. Lion-like faces are chipmunk like faces. Okay. Chipmunk like faces or lion-like faces. A line like face is a chipmunk, chipmunk like faces. And one more thing on x-ray, what you will say? The crew cut appearance. Appearance is also called as hair on end appearance. Hair on end appearance can be seen on the x-rays. That's also possible. So more RBC breakdown is happening in the reticular endothelial system. So there will be hepatosplenomegaly. Hepato hepatomegaly and splenomegalism. Okay. So they can be hepatomegaly as well as splenomegalism. Now, if you do electrophoresis, HBO electrophoresis, what can be seen, sir? How to identify beta cell measure? This is the case of beta cell measure. Do you know what happens? So HB electrophoresis. So no HBA. Little to no HBSN. No HBA. No HBA. Hemoglobin A is made up of two alpha, two beta. Beta is not there. Beta is not there. That is not a hemoglobin A. So hemoglobin A is not there. Now what else is there, sir? So the patient is going to have HBA2 levels and HBF levels are elevated. So HBA2 and HBF levels are going to be elevated, sir. Okay. So definitely it's a micro set academia. Hemoglobin production is not there, sir. Hemoglobin production. The beta globin chains are not there. So less hemoglobin. So small size RBCs. So microstatic hypochromic armies are going to be seen. Especially in this condition, the patients are also going to have something like this. Let me show you. So this patients with beta thalassemia major, they will have this kind of Pharmacy, sir. So what are these Pharmacy? These are target cells. These are target cells. They are swimming like a blue eye, right? Bully or target, target cells. So why target cells? Because say the RBCs, first of all, that's more in size. What about the hemoglobin inside the RBCs? What about the hemoglobin amount of hemoglobin inside the RBCs? Now, less hemoglobin. Now, when there is less hemoglobin, now RBC membrane is not going to be stiff, sir. Let's put it this way, like, you know, in an easy way to understand. So now the hemoglobin is not going to be there. Deficiency of the hemoglobin. When less hemoglobin is there, now RBCs are going to become very loose. Hemoglobin is not there. They are not going to be stout. They are not going to be stiff. Now inside the cell, the hemoglobin is very less. So the membrane is going to be very much loose. So now the RBC membrane will become something like this. For example, say normal RBC membrane, it's like this, sir. So inside what is there? Hemoglobin. Good amount of hemoglobin is there. Good amount of hemoglobin is there. Okay. In the periphery, you are going to have more hemoglobins. Like this. But what happens in beta thalassemia? Thalassemia, there is severe deficiency of the hemoglobin. So RBC is going to become like in the membrane is going to become loose. So that loose membranes, the loose RBC membranes can form blephs like this. They can form what can form blips? Cytoplasmic are blephs. Okay. The cell membrane blips. Okay. They are forming the blips. Now, some amount of hemoglobin will come and get deposited over here. Some amount of hemoglobin. So yes, hemoglobin is there in the periphery. Okay. But the moment of hemoglobin will also come and get deposited in the center. So now the center also you can see that red color. So that's why, sir. Okay. So target cells can be seen. Completely dependent on the transfusions. Completely that dependent on the transmission. Without Transmissions, they won't. So there is no problem during the childhood or I should say there is no problem before the six months. Okay. In neutral and six months, no problem. After six months, when the fetal hemoglobin is getting transition into the adult hemoglobin, then comes the problem. Then comes the hemolysis. Okay. These are the problems. And what else I want you to know is these patients who are having beta calcium measure. Okay. These patients who are having the betathelsemia measure, they're continuously taking the transfusions from outside. They are taking the normal RBC blood Transmissions. Okay. They're like, um, like blood vampires. They're drinking the blood. Okay. They are always, always every like, you know, for every 10 days, 12 days, they're giving and taking the blood transfusions, which means they are simply taking the iron from outside. But they are taking the blood cell from outside. They are taking the blood. So every time they are loading their body with more and more iron. Blood is nothing but iron that have hemoglobin. Hemoglobin have iron. So they are taking the iron into the body. So these patients are at risk of developing hemochromatosis. So what is the risk, sir? So these patients are at risk of developing hemo so CIS. These patients are at risk of developing hemochromatosis. That is O iron overloaded state. Iron overloaded itself. So these are some important points regarding the thalassemia. So remember the thalassemia is not a qualitative problem. It's a quantitative hemoglobin effect. Quantitative problem, which means Alpha globin, Alpha globin is deficient. Alpha thalassemia. Beta globe insufficient. Beta thalassemia. Are completed. I hope this will be enough for today. In the tomorrow's class, let's continue with the macrocytic anemias and normocytic anemiah. Tomorrow's class. So the class itself. See you tomorrow. Thank you.