 All right, so welcome back once again. Welcome back to the part two of our discussion. So we finished discussing about iron deficiency anemia and anemia due to chronic disease or chronic inflammation. So now let's move on to another type of anemia which is your cideroblastic anemia. So cideroblastic anemia is caused by blockage in the protoporphyrin pathway resulting in defective hemoglobin synthesis and even iron overload. So kung kanina, mapapansinin nyo in the iron deficiency anemia, si iron yung kulang kaya ang nangyari naipon si protoporphyrin, therefore nag-inclusive free eritrocyte protoporphyrin sa ating dogop. In this time, okay, okay naman si iron, walang problema kay iron, pero ang may problem naman ngayon is yung protoporphyrin pathway natin. What happens here is that excess iron this time accumulates in the mitochondrial region of your immature RBC in the bone marrow and encircles the nucleus and now you can see your ring cideroblast, okay? Your ring cideroblast, the one on na may pointer, those are called your ring cideroblast. What are cideroblast to start with? Cideroblast are nucleated RBC with cytoplasmic iron granules, okay? Cytoplasmic iron granules. So when we say cideroblast, nucleated RBC precursor, so this meaning to say these are immature RBCs palamang. On the other hand, we also have what we call ciderocytes, okay? So in ciderocytes, excess iron accumulates this time in the mitochondrial region of your mature RBC in the peripheral circulation and this time we call them ciderocytes. Ciderocytes are RBC with inclusion bodies called your ciderotic granules which can be stained using right stain and now we call the ciderotic granules as your pappenheimer bodies, okay? So your pappenheimer bodies are seen in your ciderocytes when stained with your right stain, okay? Yung right stain natin. So what happened in cideroblastic anemia once again? So what happened in cideroblastic anemia is this one. In cideroblastic anemia, may problema tayo sa production, okay? May problema tayo sa production ng protoporferin natin, okay? Nang protoporferin natin. In cideroblastic anemia, it can either be due to iron, it can either be due to lead poisoning. That's why in cideroblastic anemia, nagkaroon tayo ng interruption sa heme pathway natin, okay? Sa heme pathway natin. I will be creating a separate video about cideroblastic anemia and porphyria separately so that you guys will be able to identify and understand it better. But for now, I'll just give you a quick background of what cideroblastic anemia is. Again, I want you to remember everyone that in cideroblastic anemia, the hallmark of cideroblastic anemia is actually the hallmark of cideroblastic anemia. Are these ciderocytes in cideroblast, okay? In cideroblast, you can observe ring cideroblast using pearl's prussian blue stain. And you can observe ciderocytes with your pappenheimer bodies with your right stain, okay? With your right stain. So moving forward, okay? Moving forward, in cideroblastic anemia, okay? In cideroblastic anemia, again, iron. There is iron overload which I will be discussing later on in hereditary hemochromatosis and hemocyderosis. So let us first differentiate the microcytic hypochromic anemias, okay? Before we end. So as you can see, we have talasemia which will be discussed together with your porphyria. I'll be creating a separate video for that. So talasemia, we have anemia of chronic disease, iron deficiency anemia, lead poisoning, and cideroblastic anemia. As you can see, I want you to take a look at the serum iron. So the serum iron are normal to high for lead poisoning and cideroblastic anemia. Why? Kasi ang problem natin dito this time, merong kang enough iron. Si iron naman yung naipon kasi wala kang him. Unlike in anemia of chronic disease and iron deficiency anemia, si iron yung mababa, okay? Si iron yung mababa at kung titing na nyo yung FEP natin dito siya naman yung mataas, okay? Siya naman yung mataas. In cideroblastic anemia, mix yan. It can be high or low and in lead poisoning, it can actually be high. Okay, later I explain natin why in lead poisoning mataas si FEP. It's or sabi mo ang problem natin na sa pathway mamaya. I will be explaining to you why lead poisoning causes increase FEP and also normal to increase iron, okay? So TIBC, I want you to take note of TIBC, increase siya sa iron deficiency anemia, okay? Increase siya sa iron deficiency anemia but it is low in anemia of chronic disease, okay? And also serum feritin, okay? So I want you to take note of this table because it might come out as a case study in your future exams, okay? Moving forward, let's go to hereditary hemochromatosis. Hereditary hemochromatosis is the most common form of iron overload disease. So iron overload disease, your hereditary hemochromatosis is actually an autosomal recessive disorder that causes body to absorb and store too much iron. So remember, 1-2 mg of iron lang every day ang inaabsorb ng ating katawan but this time, due to hereditary hemochromatosis, your body has a mutation in the HFE gene which regulates the amount of iron absorbed from the food, okay? Amount of iron absorbed from the food. So what happen if that HFG gene is impaired? Your iron will excessively be reabsorb inside your body and it can actually be seen, it can actually cause deposition of iron in your parankayimal cells and if that iron is stored in your parankayimal cells, it can actually destroy or it can actually destroy your organ. And what organ are usually affected? Your liver, your heart, and even your pancreas. So manifestation of hereditary hemochromatosis or arthritis, liver cirrhosis, liver cirrhosis due to the deposition of iron in your liver parankayimal cells, congestive heart failure because even in your heart, some of your iron are already being stored, impotence, okay? This is very common in men with hereditary hemochromatosis, failure of men to have penile erection, impotence. We also have bronze skin. Sir, bakit po bronze skin? Bronze skin because even in your skin now, your iron has been deposited. Sir, remember yung bakal, yung bakal natin is a type of iron. So, iron deposited in your skin would also cause bronze skin, okay? Sir, bakit po may diabetes? Remember when Sir Ganding said that deposition of iron in your parankayimal cells specifically in your liver, in your heart, and in your pancreas. And once that your pancreas has been overloaded with iron, your beta cells will also be destroyed alongside with other cells in your pancreas causing now diabetes in your patient. That's why in some cases hereditary hemochromatosis may tinatawag tayong bronze diabetes or bronze skin diabetes, okay? Because why? They have bronze skin due to iron deposition and they have diabetes secondary to hereditary hemochromatosis. And we also have thyroid deficiency, okay? Thyroid deficiency. So as you can see guys, iron, kapag pakalat-kalat lang si iron inside your body, delicado din siya. Maybe some of you thought about it na to prevent iron deficiency anemia and di mag-take na lang ako ng maraming iron. No, no, no, you cannot do that because when you overload yourself with iron, it can actually be deposited in other areas or other organs of your body, therefore causing now, okay? Therefore causing now your hemochroma- causing now the destruction of your parankaymal cells. Eh sir, pano po kapag wala naman po ako ng hereditary hemochromatosis? Wala naman po ako ng hereditary hemochromatosis but I was overloaded with- I was overloaded with iron and not because of mutation. What do we call that on the other hand? We call that hemocyderosis, okay? Hemocyderosis. So remember that there are two types of iron storage inside your body. Your ferritin which is the soluble one and your hemocyderin which is the insoluble one, okay? Insoluble one. So what happened when iron content in the blood is increased? So meaning to say na karoon ka ng iron overload, okay? What will happen now is not hemochromatosis because that is hereditary. What happened is hemocyderosis. Hemocyderosis is characterized by little parankaymal cell injury. Between hemocyderosis and hemochromatosis, hemochromatosis is more severe, okay? Is more severe because it can really cause parankaymal cell injury, causing the destruction of your liver, your heart, and even your pancreas, okay? And other organs where iron is deposited. Unlike in hemocyderosis, okay? In hemocyderosis, little lang yung parankaymal cell injury, okay? And remember there are some treatments, okay? There are some treatments for hemocyderosis and also for hemochromatosis which is number one, avoiding food that contains iron. Next is phlebotomy. So what is phlebotomy? Phlebotomy, we are extracting blood from the patient to relieve iron overload. So binabawasan natin yung dogoon nila para alongside with that specimen or high iron content. So phlebotomy is also a therapy for polycythemia vera. So binasan, okay, some patients with hereditary hemochromatosis and even polycythemia vera, nag-undergo sila ng blood extraction, okay? But this blood cannot be transfused to other people kasi na abnormal yung mga cells at abnormal yung content yung dogoon. Okay, and aside from that, you also have a drug called your dysferal or your deferoxamine, okay? Your deferoxamine that lowers down iron content in your body. So that is the difference between hereditary hemochromatosis and hemocyderosis, okay? Hemocyderosis, okay? Now let's go to another type of anemia, okay? Another type of anemia, which are your megaloblastic anemia. So what are megaloblastic anemia? Megaloblastic anemias are actually DNA, defect in DNA synthesis that result to abnormal nuclear maturation, okay? So abnormal nuclear maturation. RNA synthesis is normal, so cytoplasm is not affected. It is actually your nucleus because this is a DNA defect in your RBC. Asynchronism is observed whereby nucleus matures slower than the cytoplasm. Remember that in the differentiation of your cell, your cytoplasm increases in size until it becomes pecnotic nucleus until it is already gone. But in this time, okay, may asynchronism sila. When we say asynchronism, kindi sabay na nagmamatura yung liver, yung nucleus at yung ating cytoplasm. So usually these are caused by vitamin B12 deficiency or folic acid deficiency, okay? Aside from that, laboratory findings could also be one, pancytopinya. When I say pancytopinya, this is the overall decrease in all types of blood cells, be it red blood cells, WBC, and even thrombocytes or your platelets, all are decreased, decrease bumababa. Okay, they are pancytopinya. Macrocitic normochromic anemia is observed. You can also see here oval macrosites, okay? Oval macrosites and tear drops or dachryocytes in your peripheral blood smear. Inclusion bodies can range from how old jolly bodies, nucleated RBCs, vasophilic stippling. You can also have Pappenheimer bodies and Cabot rings. So I hope all these things were discussed to you in the laboratory, in your RBC inclusion bodies, okay? Yung mga anumalis natin. So as you can see, because the DNA is the one defected. All other activities in the cell are also affected. Even other inclusion bodies can be observed in megaloblastic anemia. Again, not all the time, but you can see some of these in megaloblastic anemia. So let us go first to the first etiology or reason of megaloblastic anemia, which is your vitamin B12 deficiency or cobalamin deficiency. Vitamin B12 is actually secreted by the parietal cells. Your parietal cells secrete intrinsic factor. And this intrinsic factor in return binds to your cobalamin or your vitamin B12 in order to be absorbed in your intestine, okay? In order to be absorbed in your intestine. So meron tayong deficiency in vitamin B12, number one, if there is pernicious anemia. Pernicious anemia is caused by a deficiency of that intrinsic factor. That intrinsic factor that binds with B12 for it to be absorbed in your intestine, okay? So what are the causes of pernicious anemia? Presence of antibody against the intrinsic factor that secretes the intrinsic factor. So anong ibig sabihin mo dun, sir? Yung sa pernicious anemia, merong antibody. Antibody that is directed against number one, your intrinsic factor. Kaya yung intrinsic factor mo nasisira, okay? Secondly, there are also in antibody directed your parietal cells. Parietal cells nasisira in din yung parietal cells. Therefore, pag nasiras in parietal cells, wala ka ng magpuproduce ng intrinsic factor. So that is what happened in pernicious anemia. So since there is pernicious anemia, there will be vitamin B12 deficiency because there will be no longer intrinsic factor to carry it from the intestine into your bloodstream this time. So this is more prevalent in older adults of English, Irish, Scandinavian descent, okay? So mas prevalent siya sa mga English, Irish, and Scandinavian descent. In addition to that, it is also characterized by aclorhydra, okay? Aclorhydra and atrophy of gastric parietal cells. Bakit aclorhydra? So remember that aclorhydra is the alkaline now, acidic yung iyong stomach, okay? A state where your stomach is now alkaline or it now loses its acidity, okay? It loses now its acidity. So that is aclorhydra, okay? Aclorhydra. Aclor, nalabubulu ako. Aclorhydra, okay? So that is very important for you guys to remember, okay? Aclorhyde, this is kaya ako nabubulu, sabi ko maliya ni. Aclorhydria, okay? Aclorhydria, it should be hydria. A-C-H-L-O-R-I-H-Y-D-R-I-A. Aclorhydria, okay? Aclorhydria, okay? Absence now of your hydrochloric acid or acidity in your stomach, okay? So because of that, your vitamin B12 in return will not be, will not be, will not be, what do you call this? Will not be absorbed. It's, sir, anong kinalaman yan ngayon? Sa megaloblastic anemia, siguro that's what you're asking, okay? So remember that vitamin B12, okay? Vitamin B12 is actually coming from your, coming from your diet, okay? Coming from your diet like your animal proteins and in the meat. And then it will be bound to intrinsic factor, na dadalini intrinsic factor to be absorbed in your intestine, okay? In return, this cobalamin or vitamin B12 function in the DNA synthesis, okay? In the DNA synthesis. Bakit? Because this is a very important coenzyme, okay? It is a very important coenzyme in the conversion of your tetrahydrofolate or to become your tetrahydro, to become your tetrahydro, your tetrahydrofolate. So conversion ng methyl tetrahydrofolate to become your tetrahydrofolate, which is very important in DNA synthesis, okay? Important siya in your DNA synthesis. So in addition to pernicious anemia, makikisulat na lang po ako mga kapatin, in addition to pernicious anemia, if you do have the downloaded PowerPoint already, you can see this on the notes. Alongside with pernicious anemia, vitamin B12 deficiency can also be caused by gastronectomy. It can also be caused by defective B12 absorption, blind loop syndrome, Crohn's disease, tropical spru, and of course, your dipholebotarygium latum, your D-latum infection, okay? Your D-latum infection. I believe right now that the, your dipholebotarygium, dipholebotarygium latum has its new name already, which is your diabotryosephalus latus, okay? Your diabotryosephalus latus, okay? So yun na yung bagong name ni diapolebotarygium latum. So those are causes, aside from pernicious anemia, that causes vitamin B12 deficiency. So in general, under the umbrella of vitamin B12 deficiency, mandaming different causes. One of them pernicious anemia, your diabotryosephalus latus infection, or your D-latum infection, and also other diseases that affects the absorption of B12 inside your body. That's why eto rin yung problem. Why most of the vegetarian would need to really have a meat substitute because they need to have vitamin B12 which can own, which can be found in your meat. So napaka-important talaga na may B12, ano tayo, may B12 supply tayo. Kasi if not, your DNA synthesis in your RBC will be affected. And tingnan yun na lang, di ba? Because of that defect in DNA synthesis, there are a lot of things that went wrong in the development of your RBC. So with regard to the sequence of development, eto yun na nangyari. Nagkaroon ng decrease in vitamin levels. Nagkaroon ng hypersegmentation with your neutrophils in the peripheral blood. There's no presence of your oval macro-sides in your peripheral blood. There will become a megaloblastosis in your bone marrow. So bakit megaloblastosis again because of the asynchronous maturation of your nucleus and your cytoplasm. And eventually will become now your anemia. Okay? Become now your anemia. Sir, bakit po anemia? Because remember ang ating pancreas, lahat ang pancreas mo, the graveyard of your RBC will all destroy the old, the old and senescent RBC. RBC with abnormalities or inclusion bodies. And also, RBC that are erroneous or that are enlarged, like your macro-sides, okay? Like your macro-sides. Laging tatandaan, matanda, mapangit, mataba, papatayin ni pancreas, ang RBC na mapangit, mataba, at mapangit, mapangit, matanda, at mataba, okay? So in addition to that, when it comes to vitamin B12 deficiency, okay, when it comes to vitamin B12 deficiency, ayan, so we have malabsorption syndromes, your difilobotrium latum, which is now diobotryosephalus latus, okay, difilobotryosephalus latus, your gastrectomy intestinal blind loops, vegetarian diet, ayan, yung vegetarian diet kasi wala na silang B12 sources coming from the meat. So what are the possible symptoms? So jaundice, ayan, jaundice, weakness, sore mouth, like your glossitis na nakita si glossitis, okay, type it in, na nakita si glossitis sa iron deficiency anemia, correct? Very good. So we also have your gastrointestinal disorder, numbness, and CNS problem or your central nervous system problems. So your megaloblastic anemia, sabi natin, nasettle na natin, it's because of B12 deficiency. Another thing is because of folic acid deficiency or your folate deficiency. So symptoms almost the same with B12 except that there is no CNS involvement. Okay, yun na yun ha, yun ay yung key point natin doon. Parahas sila, ang folate deficiency at cobalamin or B12 deficiency are all the same except in folate deficiency or your folic acid deficiency, there is no CNS involvement. Okay, so this is caused by poor diet due to pregnancy, nagpufolate yung mga pregnant women natin, chemotherapy therapy that are antifolic acid like your methotrexate okay, your methotrexate na chemotherapeutic agent or chemotherapeutic drug that is antifolic acid. Sir, bakit po yung folic acid important again when it comes to when it comes to when it comes to your DNA. So remember, remember ninyo kanina di ba na si Vitamin B12, papakita ko na lang ulit sa inyo. Okay, when it comes to hindi wala pala sa power point but when it comes to your folate remember na si Vitamin B12 di ba, it is converting your methyl methyl tetrahydro furate into become folate rather to become its tetrahydro folate. Which is very important in DNA synthesis. Very important in DNA synthesis. Iking to say kapag wala kang folate also affected din yung DNA synthesis. Okay, DNA synthesis. So what are the usual sources ba ng folate? Ayyan eggs, milk, leaf, vegetable, yeast, liver and fruits. Okay, liver and your fruits. So again, Vitamin B12 deficiency is almost the same with folic acid deficiency except that in folic acid deficiency there is no CNS involvement here. Okay, no CNS involvement. So in folate folic acid deficiency so sabingan natin it came from your diet so the bodice reserve could last for only 3 months it can only last for 3 months and so most common cost of folate deficiency occurs in pregnancy is fetal requirement for folate so laging anong sinasabi deba ang mga buntis hindi na lang ko makain for themselves but for two persons sa nani at of course sa baby na daladala niya and that is very true. Okay So in addition to that everyone, in addition to that there is also a non-migaloblastic macrositic anemia. Okay macrositic anemia which are seen into conditions which are number one, your alcoholism and your liver disease. Okay liver disease and alcoholism so meaning to say walang involvement yung DNA, walang problem hindi siya magaloblastic walang magaloblast sa sa bone marrow rather there are macrositic cells, macrositic rbc due to non-migaloblastic non-migaloblastic etiology such as alcoholism and liver disease. So for today we actually did discuss iron deficiency anemia, anemia for chronic disease or inflammation. I did discuss to you hereditary hemochromatosis and hemocyderosis already migaloblastic anemia and an introduction of cideroblastic anemia. So for today that is the end of our discussion so thank you so much. So I will be posting all the links for this videos, also the notes are already uploaded in your TLC and at the same time sitworks will be coming up for this particular topic and please return to the Google Meet for your questions which I will be entertaining before our meeting ends. Again, thank you so much. So I'll see you guys on our Google Meet. So see you there. Bye.