 Okay, good morning everyone, good afternoon, good evening whatever time you're watching this video right now, so a pleasant day to everyone. So for today we will actually be starting our new discussion on hematology and that will be about intrinsic and extrinsic defects leading to your increased eritrocyte destruction. So whether it is intrinsic or extrinsic or anything that causes your RBC to actually have an increased destruction, we're going to talk about it for today. So before we start, may I remind everybody to please make sure that you have a copy already of the PowerPoint presentation that I have so that as you go along this video for this morning you would be able to follow along our discussion and by the end of this there will be a sit work which you will be answering by the end of today. So I'll be giving you a sit work for hematology for today. So before we start again I just want to greet everybody and I just hope everyone is doing well today. So to start with let's talk about your hemolytic or your hemolysis first. When we talk about increased destruction of your RBC it can either be in different forms, it can be acute or chronic, it can be inherited or acquired, it can be intrinsic or extrinsic and even intravascular or extravascular hemolysis. So for today what we're going to talk about is a different classification of anemia. So why do you call it anemia? So please do remember that when there is hemolysis or increased destruction of your RBC, your RBCs now originally, 120 days yung lifespan ng ating RBC. But because of increased destruction of your RBC they are prematurely lives. They do not even reach 120 days bago sila na de-destroy. So we can classify your hemolytic anemia into two. It can either be acute or chronic hemolytic anemia. When we say acute hemolytic anemia and chronic hemolytic anemia, we're talking about the onset of the disease and the onset of the signs and symptoms. So usually in acute hemolytic anemia, your signs and symptoms, the hemolysis occurs rapidly or upon exposure to a particular trigger, a particular substance or a particular condition or environment, your red blood cells now will start to lies. So agad-agad siya pagka-expose, magkakaroon agad ng hemolysis. Unlike your chronic, your chronic can even be undetected at times. Why? Because sometimes your bone marrow still can compensate to the loss of RBC that is happening. So lagi naman ganun di ba, your bone marrow will try to compensate the loss of your red blood cells through your eritropoasis. So until the bone marrow is already overwhelmed by an increased hemolysis of your RBC, that is the time now, that is the only time lang na magkakaroon ka ng anemia or na magiging evident yung anemia mo. So technically what happened is that the accumulated or the accumulated burden over time in your chronic hemolytic anemia would now present itself as a condition over time. So that is acute and chronic. Let's move forward to intrinsic, rather inherited and acquired hemolytic anemia. In your inherited hemolytic anemia, what happened here is that what happened in your hemolytic anemia is that inherited hemolytic anemia, what happened is that the factors that lead to the increased destruction of your RBC are actually within your RBC or hereditary. So talagang pag kapanganak mo palang, talagang predisposed ka na or predestined ka na into having hemolytic anemia. Unlike kapag acquired yan, if it is acquired upon exposure to a particular substance, upon exposure to a certain condition or environment, that is the only time where your RBC would start now to lies. Unlike apag inherited or hereditary, talagang meron ng factors, may factors na within your body, within your RBC that actually lead to increased destruction of your RBC. So moving forward on to that, moving forward, it can also be intrinsic and extrinsic. So intrinsic and extrinsic is somehow similar to inherited and acquired. Most of your intrinsic factors that leads to increased RBC destruction are actually inherited. Kadalasan yung mga intrinsic are also inherited. What do we mean ba when we say intrinsic? We mean we say intrinsic since your RBC, the problem is within your RBC. So later on, I'll try to give you two common intrinsic factors that leads to increased RBC destruction. On the other hand, we also have your extrinsic. Usually these are acquired conditions. When we say acquired conditions, you are exposed to a particular substance, you're exposed to a particular bacterial or viral infection that will lead now to an increased destruction of your RBC. So meaning to say RBC sa RBC, normal naman yung RBC mo. It's just that your RBC was exposed to certain conditions that will now increase its destruction. So that is for your extrinsic and extrinsic. What about intravascular and your extravascular hemolysis? Your intravascular hemolysis is also known as your fragmentation. In your intravascular hemolysis, yung lysis ng cells or ng RBC mo happens in your blood vessels. That's why we call it intravascular. So intravascular hemolysis can happen due to various conditions. It can either be due to mechanical disruption sa flow ng blood. It can even either immunological. So pwede rin immunological. Merong antibodies or mga autoantibodies and even complement activated that cause your RBC to lies. On the other hand, it can also be extravascular. When we say extravascular, it is macrophage mediated, meaning to say it's outside your blood vessel and usually these happen inside your spleen. It happens inside your spleen. So on your screen right now, you can actually see that your RBCs, okay, your RBC, the RBC destruction can be classified as to extrinsic and intrinsic. And as you can see, most of the extrinsic causes are also the acquired conditions. The intrinsic defects on the other hand are usually the hereditary or the inherited conditions. And those that you can see on your screen that are colored red, those are usually chronic by nature. So over time, slow phase yung hemolytic animya na yan. Unlike your, unlike your green ones, these are your acute or episodic hemolysis. So as you can see, bakit natin sinabing episodic? Episodic because makakaroon ka lang ng hemolysis kapag na-expose ka sa certain extrinsic defects or extrinsic or acquired conditions that will lead now to hemolysis. But for today, okay, ladies and gentlemen, let us first discuss the intrinsic and the intrinsic defects leading to increased erythrocyte destruction. And when we are talking about this, there are, there are actually two main thing that I want you to remember. And these are what? These are RBC membrane abnormalities and RBC enzymopathies. So it can either be problem in two things, the membrane and the enzymes within your RBC. So sa membrane natin, so matatandaanin nyo your RBC kasi, your red blood cells, so let's talk about the membrane first. Your membrane needs to be deformable. So meaning to say your RBC should have deformability because it will pass through different blood vessels, small blood vessels within your body. Enzymopathies on the other hand, because lack of enzymes, so lagi, lagi, lagi kong nire-remind before, that you have to make sure that the enzymes are also complete because if the enzymes is lacking, the product will not be produced. And kapag ang product hindi na produce, there is now a problem inside your RBC. So we'll talk about that in a short while. But before that, let us now move forward to hereditary RBC membrane abnormalities. What are the different abnormalities? It can be two. It can either be a mutation that leads to the alteration of your membrane structure and mutation that alter your membrane transport proteins, your membrane transport protein. So anong pinagkaibanong dalawa? Yung isa yung ismong structure ng RBC membrane mo. Pangalawa naman is yung transport protein sa RBC mo. So this has something to do with the cataion exchange, yung pagsinabi natin transport protein, yung nagpapasok labas ng mga molecules in and out of your RBC. But let us first discuss your alteration in the membrane structure. So before we dig deeper into that, please do remember that there are, with regards to your RBC membrane structure, there are transmembrane proteins and cytoskeleton that are responsible in this, that are responsible for this function. And what are those? Okay, what are those? Let's start with the four proteins that has a significant role in the structure of your red cell cytoskeleton. So we have your spectrin. Your spectrin is a major cytoskeletal protein that maintains the cell membrane or your red blood cell shape. The biconcave shape is being maintained by your spectrin. On the other hand, we also have here your ankerin. Your ankerin serves as an anchor that whereby your spectrin molecules will be assembled on your lipid bilayer. So what happened here is that your ankerin, together with your actin and your band 4.1, all those are your anchors. What do you mean by anchors? Sila yung foundation. Sila yung foundation kung saan maga-assemble ang spectrin natin. So kung walang ankerin, walang spectrin. Kasi walang kaka-kapitan or walang anchor na paglalagyan yung ating spectrin. Why do we have color coding? Because your ankerin and your actin, these are transmembrane protein. They are transmembrane protein that are responsible for the vertical interactions on your red blood cell membrane. So what do we mean by that? So look at this picture, everyone. So your transmembrane protein meaning to say sila yung parang nakapangchore sa iyong red blood cell, sa red blood cell membrane mo. So as you can see, we call it vertical because yung interaction nila is vertical. The ankerin and the actin are vertical. So vertical yung interactions nila from with one another. So they maintain the vertical interaction. The vertical interaction in your red blood cell prevents the loss of membrane. Prevents the loss of your membrane para itong luck para siyang isang anchor or isang anchor that prevents your ship or your boat from being taken away by your current. Same thing with your ankerin and your actin. They serve as a transmembrane protein that anchors your membrane and prevents its loss over time. So that is your ankerin and your actin. Ano naman ang ganap ni spectrin? If your ankerin and your actin are transmembrane protein responsible for the vertical interaction, your spectrin are cytoskeletal protein that maintains your cell shape. And they are responsible now for the lateral or the horizontal interaction. So kung makikita ninyo yung yellow at yung red band natin dito, these are your alpha and your beta spectrin. They are responsible in the horizontal yung pahiga, the lateral interaction on your cell membrane. And what are their function? They function by preventing or by maintaining your cell shape, the biconcave cell shape. What happen now if there is a problem with these four cytoskeletal protein and transmembrane protein? What will happen? What will happen is the most common membrane defect which we call your hereditary sphero cytosis. Your hereditary sphero cytosis is the most common membrane defect in which there is an increased permeability to your sodium. Increase permeability to your sodium which now results to a loss of your membrane. So sabingan natin kanina, your spectrin, your ankyrin, your actin, they all work together to prevent loss of your membrane and to maintain your cell shape. Pero dahil may problema dito, mawawala yung ating membrane. Mawawala yung ating membrane causing now an increased permeability to your sodium. So instead na hindi makakapasok agad si sodium, nakakapasok siya dahil wala na yung mga transmembrane proteins. In addition to that, in addition to that dahil wala ka na rin membrane dahil wala ka ng ankyrin kung saan doon na kaankor ang iyong assembled alpha and beta spectrin, what will happen is that the shape will also be lost. That is why in hereditary sphero cytosis, you will no longer see RBC that are by concave in shape but rather you will see sphero sites that has spherical shape RBC. So again, there is a defective binding mga spectrin to your protein 4.1 dahil wala ka ng ankyrin to start with. So your hereditary sphero cytosis can either be a mutation on either of those cytoskeletal protein and transmembrane proteins that we were discussing a while back. So it can either be a mutation in your ankyrin, your SPTA1, your SPTB, and your EPB42 which codes for your ankyrin, alpha spectrin, beta spectrin, and your protein 4.1 respectively. So what happened during this time is that your RBC now will have an increased fragility, okay, an increased fragility which leads us now to its screening test which is your auto hemolysis test. Okay, auto hemolysis test and a confirmatory test for your hereditary sphero cytosis which is osmotic fragility test. So remember, okay, remember that in your RBC originally, kapag expose ang RBC mo sa isang hypotonic solution, it will just swell but it will just swell, okay, and that is for a normal RBC. But for RBC that has hereditary sphero cytosis, your sphero sites will have an increased osmotic fragility. So ano pung ibig sabihin natin pag increase osmotic fragility, they are more fragile compared to your normal RBC. Okay, so when exposed to a hypotonic solution, automatically kung yung normal hindi pa pumupotok sa pagkakataon na yun, ang mga hereditary sphero sites, ang mga hereditary sphero cytosis patients natin, yung kanilang sphero sites will automatically start to lyse upon exposure to a hypotonic solution. So there are also new, aside from increased osmotic fragility, you would also observe numerous micro sphero cetic RBC in your peripheral blood smear. So what do you mean by micro sphero cetic? Micro sphero cetic, so remember, nagkaroon na tayo ng loss ng membrane because of your ankyrin mutation, so dahil doon na wala yung membrane, lumili it yung RBC natin. Okay, pero lumili it siya, pero hindi pa rin siya by concave shape. That's why we don't call it your micro by concave RBC, but rather we call it micro sphero cetic RBC that are seen in your peripheral blood smear. In addition to that, one important thing for you to remember is that in cases of hereditary sphero cytosis, your MCHC is also increased. So this is a unique feature in your hereditary sphero cytosis. So moving forward now, okay, so alam ninyo na ang hereditary sphero cytosis may problem tayo sa ating cytoskeletal protein at sa ating trans membrane protein. So may problem talaga sa ating membrane. Next is your hereditary elliptocytosis. What happened in your hereditary elliptocytosis, ladies and gentlemen, is that there is a defect on your membrane. Why? Because your RBC now will start to become elliptical by shape. They will start to be oblong in shape. And what is that for what reason? That is because of the polarization of your cholesterol at the ends of your cell rather than around the pallor area. So instead na sa pallor area siya nag-nag-nag-nag-nag concentrate yung cholesterol mo, it concentrated itself on the both ends of your RBC. So para siyang naging oblong talaga siya. So your hereditary elliptocytosis is actually the second most common membrane abnormality, okay, intrinsic membrane abnormality. And this is usually present in only 10 to 15 percent cases of anemia. So again, your hereditary elliptocytosis would be characterized by 25 percent of elliptocytes in your blood film or your peripheral blood smear, okay? So that is your hereditary elliptocytosis, your cholesterol polarized at the ends of your RBCs. Now we go to hereditary stomatocytosis. Your hereditary stomatocytosis has an abnormal permeability with both your cataions, okay, with both your cataions which are your sodium and your potassium. What happened here, okay? What happened during stomatocytosis? What happened during stomatocytosis or also known as your hereditary hydrocytosis, okay? Your hereditary hydrocytosis is that your RBC membrane is excessively permeable now to your potassium and your sodium. So because of that, the influx now of your sodium into your cell will now cause loss of your potassium. So what happened here is that your RBC now will start to swell. Your RBC will start to swell forming what we call your stomatocytes, stomatocytes or your mouth cell, okay? Stomatocytes or your mouth as in bunganga, okay? Your stomatocytes or your mouth cell. This is actually, and the shape is actually like a lip, para siyang lips, okay? Ganon yung itchura ng RBC natin kapag may stomatocytosis. Although, makikisulat po ako sa inyong mga notes right now, that stomatocytosis can also be acquired. Stomatocytosis can also be acquired because of acute alcoholism, okay? Acute alcoholism. So moving forward, we also have here your hereditary acantocytosis. Your hereditary acantocytosis is due to abeta lipoprotinemia. So meaning to say, the absence now of your serum beta lipoprotein needed for your lipid transport leads now to the formation of your acantocytes. Your acantocytes are formed due to an increased cholesterol-lesitin ratio in the membrane, due to abnormal plasma lipid concentration. So instead that your cholesterol is being carried by your LDL or your beta lipoprotein, it is now being attached to your RBC. Na-attached sila sa RBC mo, therefore the cholesterol-lesitin ratio increase, causing now the formation of your acantocytes. Ang acantocytes mo are like pseudopods para siyang mga finger-like projections sa ating RBC. But unlike other, like your Bercel, okay? Unlike your Bercel, your acantocytes, okay? Your acantocytes are actually irregular. Irregular yung projections nila. So when I say irregular, hindi pan-tay-pan-tay yung mga projections na meron tayo sa acantocytosis. So remember that because there is absence of beta lipoprotein, yung cholesterol mo dumikit sa RBC at dahil dumikit sa RBC, it can now cause your what? It can now cause an increase-lesitin to cholesterol-lesitin ratio forming your acantocytes, which are known to be hereditary, which are known to be hereditary acantocytosis, okay? Hereditary acantocytosis. So moving forward, siguro magtataka kayo, let's try to differentiate stomatocytosis and spherocytosis. Spherocytosis increase sa permeability ng sodium, pero ang ating stomatocytosis, both sodium and potassium. Paghiwala yung din natin si acantocytosis at si elliptocytosis, kasi parayas silang may kinalaman sa cholesterol. Sa elliptocytosis ang may problema ay yung RBC membrane mo, okay? Ang may problema si RBC membrane mo. In your hereditary acantocytosis, ang problema ay dahil walang betalipoprotein at dahil walang betalipoprotein, what happen is the formation of acantocytosis because your red blood cells now are being concentrated with your cholesterol. So moving forward, so those are the usual intrinsic factors that are related with the cell membrane or the RBC membrane. Now we go to the different types of intrinsic factors that leads to increase RBC destruction, which are enzymeopathies in nature. So the first one is your glucose 6-phosphate dehydrogenase deficiency. So this is a sex-link enzyme defect, which are most common defect in the hexose monophosphate shunt. So paki kitandaan that your glucose 6-phosphate dehydrogenase is a very important enzyme in your hexose monophosphate shunt. Sir para sa nangapos si hexose monophosphate shunt, your hexose monophosphate shunt prevents the oxidation of your hemoglobin by your free radical such as your peroxides. So dahil nga meron kang hexose monophosphate shunt at dahil meron kang G6PD, napiprevent mo yung denaturation ng ating hemoglobin that will lead to the formation of your Heinz bodies. So kapag may G6PD ka naman, may glucose 6-phosphate dehydrogenase ka, walang problema dahil mapiprevent mo yung denaturation ng iyong mga hemoglobin. But what happened in your G6PD deficiency, deficient ka sa glucose 6-phosphate dehydrogenase. So what happened is that your hemoglobin will be denatured, forming now your Heinz bodies. Your Heinz bodies are RBC inclusion bodies that are originally denatured hemoglobin. So your G6PD deficiency can be seen in black people which are usually mild deficiency lang in the orientals or the Asians usually more severe compared to your black people the Mediterranean has a more severe G6PD deficiency. So again in your red blood cell, in your red blood cell, in your peripheral blood smear, you can actually see Heinz bodies and you can also see their bite cell. Bakit po nang karo ng bite cell dahil sa Heinz bodies, your RBC with your RBC inclusion, inclusion na Heinz bodies will now pass through your spleen and we all know that there are two processes that are being done in your spleen, your splenic pitting and your splenic culling. So anong nangyari kay Heinz bodies, yung Heinz bodies ay isang imperfections at tantandaan ang hemo ang ating spleen, papatayin niya, pupuksayin niya, lahat ng mapangit, matanda at matabak. At dahil ang Heinz bodies is an example of mapangit na feature, what will happen is that your RBC, your splenic macrophage will pit or will bite your RBC forming now your bite cell. Yung RBC na parang kinagatan, yun yung tinatawag natin mga bite cell. So what will happen to your bite cell? Your bite cell will pass through your blood vessels again, it will room around your body until it pass through your spleen again whereby makikita na naman ni spleen na may mapangit, matanda at matabak in the form of your bite cell and it will now lies your bite cell which we call now your splenic culling. So that is your splenic pitting and splenic culling, C-U-L-L-I-N-G. So that is your splenic pitting and splenic culling. So due to the deficiency of or the absence of your glucose 6-phosphate dehydrogenase, usually wala na mga problema. What usually it's harmless, not unless you are exposed to reducing and oxidizing compounds such as your premakin, your sulfonamide, your nitroferans, your sulfones, your analgesics and antipyretics and your fava beans. So if you're exposed to these particular compounds, your hemoglobin will be oxidized and when it happens, your hemoglobin will denature forming now your Heinz bodies. Sir, bakit na poulit na denature yung hemoglobin ko? Kasi wala kang nagprevent ng oxidation. Bakit wala kang nagprevent ng oxidation? Dahil wala ka ng glucose 6-phosphate dehydrogenase. So moving forward, normally in a normal patient, we have two isoenzymes of your G6PD or your glucose 6-phosphate dehydrogenase. We have your A and B enzymes. So they differ from one another dahil sa electrophoretic mobility and when it comes to glucose 6-phosphate dehydrogenase deficiency, there are two G6PD that are very much distinct. These are your G6PD A- which are electrophoretically similar to your G6PD A. Ang problem lang hindi siya functional similar to your G6PD A. So nandun siya pero wala siya ang function. Alam niyo yung parang nandyan siya pero wala ng ganap. Unlike your and on the other hand, you also have your G6PD mediterranean. So remember, mediterranean is the most severe type of glucose 6-phosphate dehydrogenase deficiency this time your G6PD mediterranean kamukha ni G6PD B. Pero ang problem natin dito it's also abnormal. So once that your patients specifically the mediterranean that has your glucose 6-phosphate dehydrogenase deficiency ingested your phava beans, your hemoglobin will start to the nature and if it start to the nature it will form now your it will form now your Heinz bodies and we call that exposure ng ating phava beans we call that phabesem okay. So please take note that phabesem is not associated with glucose 6-phosphate dehydrogenase A- only with your G6PD mediterranean okay only in your G6PD mediterranean so we're down with the first enzyme deficiency the next one is your pyruvate kinase deficiency your pyruvate kinase deficiency is an autosomal recessive disorder so the most common enzyme this is the most common enzyme deficiency in the M then mayorhoff pathway kung si G6PD ay sa hexose monofosphate shunt si pyruvate kinase naman ay sa M then mayorhoff pathway so why is M then mayorhoff pathway important because this is the production of your ATP in your RBC dahil nga po wala kang may tochondria dito na kasalalay yung energy production ng iyong RBC at saan po ba importante ang energy energy or your ATP is important in the transport of your cat ions your sodium and your potassium more specifically your cat ion pumps okay so because that because of the lack of ATP hindi ngayon gagana yung cat ion pump mo at kapag hindi guma na yung cat ion pump mo magkakaroon ka ng abnormality in the level of your sodium and your potassium which will now lead to the decrease deformability of your RBC and that decrease deformability in your RBC will now lead to the decrease lifespan of your RBC na hukuha so dahil walang energy walang energy yung cat ion pumps natin that controls your sodium and potassium levels are also abnormal and because of that the RBC will now lose its deformability it can now it can no longer be as be flexible as possible as needed and because of that it will now have sabingan natin lahat ng mapangit matabaha at matanda lahat ng may flaws ay magkakaroon ng decreased lifespan so your um in your pyrovate kinase deficiency his severe hemolytic anemia and reticulocythosis and echinocytes are very much evident okay so that is for your pyrovate kinase deficiency now let's go to the second to the last one which is your paroxysmal nocturnal hemoglobinuria also known as your PNH what happened in your PNH PNH is an acquired membrane defect okay it's an acquired membrane defect so RBC membrane has an increased sensitivity to complement binding so review lang tayo ng konte sa inaral natin sa protein what is the goal of complement again the goal of complement is to cell lysis cell lysis complement activation so anong problema ngayon dito sa paroxysmal nocturnal hemoglobinuria the problem here guys is that there is a deficiency in the expression of your glycosyl phosphatidil inositol or your GPI your GPI are anchors your GPI are also anchors this GPI are the foundation or the anchors of your CD 55 and your CD 59 what is CD 55 and CD 59 your CD 55 is called your DAF or your decay accelerating factor and your CD 59 is your Merl or your MIRL or your membrane inhibitor of reactive lysis okay membrane inhibitor of reactive lysis or your Merl so your CD 55 and your CD 59 prevents the activation of your complement in your RBC bakit niya pineprevent kasi nga ayon natin maglice yung RBC kasi pag naglice si RBC magkakaroon ka ng increase destruction of your eritricides leading to anemia in later time so what happened in paroxysmal nocturnal hemoglobinuria once again is what what happened in your paroxysmal nocturnal hemoglobinuria your RBC okay lack the expression of your GPI anchors at dahil wala kang GPI anchors your CD 55 and your CD 59 cannot be expressed in your RBC membrane at anong mangayare kapag wala kang CD 55 at CD 59 your RBC will be will be pop it will be pop and it will now lies so your CD 55 and your CD 59 ladies and gentlemen are very important um are very important um factors or components that will prevent complement activation at kapag may complement activation anong mangayare sell lysis okay sell lysis so um sabihin na natin your CD 55 and your CD 59 are like identification cards so these are like identification cards nakapagwala kang identification card you will be eradicated you will be killed okay you will be destroyed so parang ganun lang yan okay parang ganun lang na kano rin may complement dyan sa blood mo lumapit sa RBC pero nakita na the act na inactivate ng CD 55 at 59 mo yung yung complement walang lysis na mangayare pero ang problema nga sa paroxysmal nocturnal hemoglobinuria wala ka ng CD 55 wala ka pang CD 59 anong mangayare magkakaraon ka ng sell lysis because of complement activation and what do we use to detect this um type of condition we use your hams test and we also do your sugar water test your sugar water test makikisulat po mga kapanaling your sugar water test is a screening test for your paroxysmal nocturnal hemoglobinuria and your hams acidified serum test yun yung mas completo nyang pangalan your hams acidified serum test is the confirmatory test for your paroxysmal nocturnal hemoglobinuria do not worry about the test or the procedure because we will be discussing that next meeting when we go to the hematological procedures that are very important in hema one so moving forward okay let's go to the last intrinsic defect okay and we call this your hereditary pyro poikilo cytosis this is earlier this order accompanied by a severe anemia and extreme poikilo cytosis what is poikilo cytosis differences in their p p p p p poikilo cytosis that is different differences in their shapes shapes p poikilo cytosis unlike your aniso cytosis your aniso cytosis s is differences in their s size poikilo poikilo cytosis difference in their shapes letter p okay there is severe poikilo extreme poikilo cytosis and red cell thermal sensitivity what do we mean by red cell thermal sensitivity your normal red blood cells will fragment at around 40 90 degree centigrade okay in vitro yan ha your rbc will um will actually fragment at 49 degree centigrade but for hereditary pyro poikilo cytosis mas sensitive siya mga kapatid dahil as low as 45 to 46 centigrade magfafag fragment na ang inyong red blood cells so that is for your hereditary pyro poikilo cytosis pyro poikilo cytosis so what we just discussed today are the different intrinsic defects that will lead to an increase destruction of your rbc so before we proceed with the hereditary the extrinsic defects leading to increase erythrocyte destruction let us meditate first okay so exhale everyone hold okay inhale hold o deba para lang tayong ano exhale hold and now for one last time inhale hold exhale hold and now before we proceed to our next topic so um we will be discussing the extrinsic defects now leading to an increase erythrocyte destruction okay so what are the different extrinsic defects leading to an increase erythrocyte destruction so before we start with this one so i just want to um remind everybody that um all um all of the extrinsic factors or immune defects cause anormocytic normochromic anemia normal yung rbc walang problem sa rbc the problem is what all are acquired disorders that accost now an accelerated destruction with reticulo cytosis what do you mean by accelerated destruction of what accelerated destruction of your red blood cells let us go to the first one which is your warm autoimmune hemolytic anemia so sabihin explain ko mo na pag sinabi natin autoimmune you produce autoantibodies what are autoantibodies autoantibodies are antibodies that destroy your own sinisirya niya yung sarili mong katawan okay yung sarili mong katawan that is what we mean by autoimmune ibig sabihin you produce the auto antibody directed against your body and that will now lead to hemolytic anemia sir bakit po warm hindi ko po maintindihan bakit po warm warm um antibody is your immunoglobulin g why do we call it warm antibody because your immunoglobulin g is most active at 37 degree Celsius makikisulat ako your immunoglobulin g is most active or most potent at room at body temperature which is 37 degree Celsius so what happened here is this your rbc now okay your rbc are coated with your immunoglobulin and your complement leading now to membrane loss and spherocytosis so what happened kasi kapag may immunoglobulin na naka attach sa rbc mo kahit meron kapang cd 59 at cd 55 kikilalanin yan ng complement mo as kalaban so dahil sa immunoglobulin mo or complement na nakadikit sa rbc mo magkakaroan ka ng hemolysis this are usually common in your cll or your chronic lymphocytic leukemia in your lymphoma and even exposure to some drugs okay so anong nangyari may antibody anong antibody warm antibody sino si warm antibody si igg si igg nakadikit kay rbc kaya para siyang naging target para itong naging target sa rbc na nagsasabi dahil nga may antibody sa rbc this is for destruction okay this is for destruction so again that is autoimmune meaning to say ikaw yung nagproduce ng sariling antibody that will destroy yourself so that is an immune defect so that is your why ha which is your warm autoimmune hemolytic anemia bakit siya warm kasi igg is most potent or most active at 37 degree celsus compared to your kaya si kaya is cold autoimmune hemolytic anemia katulad din siya tama katulad din siya ng warm autoantibody anong pinagkaiba yung isa warm yung isa cold sir bakit po cold nakikita nyo na siguro yung pagkakaiba that is because of the igm the igm is most potent at four degree celsus or at cold temperature or at refrigerated temperature so igm is most active or most potent at four degree celsus that's why um we call it cold autoimmune hemolytic anemia so the antibody is the antibody present is usually anti eye okay anti eye so your cold autoimmune hemolytic anemia can be secondary to your mycoplasma pneumoniae infection lymphoma or infectious mono nucleosis or your eye m okay or your eye m ano naman nangayari dito in cases take for example na na napunta ka sa mga cold cold environment napunta ka sa cold environment pag nasa cold environment ka yung igm mo didikit ngayon sa iyong mga rbc okay didikit ngayon sa iyong mga rbc at kapag dumikit si igm sa iyong rbc magkakaroon ka rin ang magkakaroon ka rin ang celsus at dahil sa celsus na yan magkakaroon ka ngayon ang ano hemolytic anemia at decrease rbc eventually okay so that is we are cold um autoimmune and your warm autoimmune hemolytic anemia on the other hand we also have the third one which is your paroxysmal cold hemoglobinuria or your pch your pch is characterized by the presence of a biphasic igg which is called your donut landstainer antibody okay your donut landstainer antibody has a p specificity that fixes complement to rbc in cold temperature okay in cold temperature and that is less than 20 degrees Celsius so take for example na sa america ka na sa alas ka ka malamig so ang mga yari dun yung igg mo sabi nga natin di ba originally your igg is warm autoantibody but in this case because of um paroxysmal paroxysmal cold hemoglobinuria your igg is biphasic so what do we mean by biphasic at cold temperature dumidikit si igg mo your donut landstainer antibody it will attach itself to your rbc okay so nandun ka sa malamig dumikit yung yung donut landstainer antibody mo sa inyong mga rbc so sabi na natin di ba in in the states in the states meron siya lang warmer meron siya lang mga um um what do you call this warmer or humidifier basa something like that okay that will warm themselves so take for example pumasok ka naman ngayon sa isang temperature na medyo mas mainit sabi na natin parroom temperature which is 37 degrees Celsius what will happen dahil dumikit na yung igg mo dun sa rbc nung na sa malamig ka ngayong pumasok ka sa isang environment na may 37 degree Celsius or na warm yung yung rbc what will happen is that what what will happen is that the rbc will now lies the rbc coated with your compliment will now start to lies sir bakit po bakit po ba may compliment kasi lagi yung tatandaan kung nasaan yung yung antibody doon pupunta rin si compliment para i destroy kung ano mang sell you on okay kung ano mang sell you on so your paroxysmal cold hemoglobinuria is secondary to viral infection and again it is characterized by the presence of your donut lancetiner anti body okay so i hope i'm clear so if i'm if you have any questions and clarifications please um do rewind this video for you to understand if not you can have your questions later by the end of our discussion so moving forward aside from why ha kayha and paroxysmal cold hemoglobinuria we also have your hemolytic transfusion reaction so hemolytic transfusion reaction is due to um abo incompatibility so recipient okay yung recipient natin may antibody against your donor so take for example ikaw ay type o okay ikaw ay type o kung type o ka anong antibody meron ka meron kang anti a at anti b pero ang na transfused tayo na dugo is type b so dahil may anti um anti b ka an anti b antibodies ka what will happen it will attack the red blood cells that has your b antigen and it will start to lies okay so basta incompatible yung dugo na na isalin sayo you call we call that hemolytic transfusion reaction okay so for now i will just be discussing to you abo incompatibility but in reality hindi lang po a b um and each antigen yung ating tinitignan there are a lot of antigen in your rbc that needs to be screened okay so in your hemolytic transfusion reaction yung recipient yung sinalinan ng dugo may antibody against dun sa dugo na isinalin sa kanya so para ang nangyari dito ka away mo yung isinama sayo sa isang room so anong nangyari nag away kayo at nag anong nangyari na destroy ninyo yung isat isa okay so in hemolytic transfusion reaction it can trigger your dic or your disseminated intravascular coagulation which will now release tissue factor and will now start to lies your red blood cells okay will start to lies your red blood cells that is your hemolytic transfusion reaction due to incompatibility in blood transfusion now we're nearing the end we also have here your hdn also known as your hemolytic disease of the newborn hemolytic disease of the newborn is not because of transfusion but because of rh or abo incompatibility paano po nagkarao ng incompatibility the incompatibility happened between your mother the pregnant mother and the fetus or the baby okay the hemolytic disease of the newborn in your rh incompatibility and your abo incompatibility um please remember that the type of immunoglobulin that is present here is actually your immunoglobulin g and your immunoglobulin g babalikan natin yung leso natin kahapon sa protein in your immunoglobulin your ig can cross your placenta nakakatawid siya sa iyong placenta and because it can cross your placenta it can affect your fetus so it will bind to your fetal rbc and it will lyse sisirain na yung rbc ng iyong sisirain na yung rbc ng iyong fetus much of the hemolytic disease of the newborn will it will be further discussed when we go to your blood banking next semester okay so um with everything that i have said okay with everything that i have said we still have a few um we still have a few um causes of extrinsic rather we still have a few um extrinsic causes of hemolytic aninia but already non-immune so pag sinabi kong non-immune wala ng kinalaman si autoantibody wala ng kinalaman si igg igm wala ng kinalaman yung ating mga antibodies okay wala ng kinalaman yung ating mga antibodies but this time it's non-immune but still extrinsic meaning to say ang problema wala pa rin sa rbc and the first one here is your maha okay your maha so all of these are also normocytic normochromic ang mga red blood cells natin but all are also acquired this order due to intravascular hemolysis with schistocytes okay so schistocytes or your fragmented rbc in some is um in some resources this is schistocytes schistocytes letter z okay so in maha or in your micro angiopathic hemolytic aninia nagkakaroon tayo ng disseminated intravascular coagulation okay intravascular um hemolytic uh intravascular the disseminated intravascular coagulation is example is in your liver disease what happened is that nagkakaroon tayo ng fibrin clot sa blood vessel natin so imagine ninyo para siyang um nakapunod daba kayo ng james bond movie na kung saan may laser sa pupuntahan mo and you have to pass through that laser laser without touching it konde makakat or masusugatan ka or tutunog yung alarm parang ganun dun sa micro angiopathic hemolytic aninia in the case of your dic there are some fibrin clots already on your blood vessel and when your rbc pass through that nakakat or nahahate okay nahahate yung ating mga red blood cells forming now your fragmented rbc also known as your schistocytes okay you can also see that in your in your h us specifically in patients okay specifically in patients with e coli infections among children so your h us okay your h us is usually um it is usually commonly seen okay it is commonly seen in your patients with um e coli infection so aside from that we also have your your ttp okay your ttp so in your ttp ganun din yung nangayari okay you're in your ttp ganun din yung nangayari i by the way your h us is hemolytic uremic syndrome okay hemolytic um hemolytic uremic syndrome so in your hemolytic uremic syndrome it that is due to a certain strain of your e coli or your eskikia coli that would lead now to your ano that will lead now to your what do you call this that will lead now to your um that will lead now to maha which is your um which is your micro angiopatic and micro angiopatic hemolytic anemia so moving forward we also have here your ttp what is your ttp makikisulat na lang ako kasi wala jyan that is your trombocytic trombocytopenic purpura okay hindi ko tinatawag si jordan ha we are talking about the trombocytobotic rather trombotic trombocytopenic purpura so this is due to the deficiency of your enzyme adam that's mean no lang you know i'm just joking that's not me your adam ts 13 that breaks that that break down your um that break down some of your that break down some of your one willy brand factor or your your your your one willy brand factor is a coagulation factor so na activate nakaakaroan ng coagulation so anong nangyayari pag nakaaroan ng coagulation yung pa yung fibrin clot are like thread like na or parang laser like that when you're rbc pass through that they will break okay they will be fragmented they will be broken down into tiny pieces yes and now for the last part we have your march hemoglobinoria okay your march hemoglobinoria occurs after about the body has a forceful contact with hard surfaces so take for example for maraton for maraton runners for tennis player so these are usually um due to forceful activities or forceful contact with your um forceful contact with um surfaces march hemoglobinoria and the last but not the least we have external other extrinsic factors that lead to increase rbc destruction we have your infectious agent like your plasmodium falsiparum even though your plasmodium falsiparum are intracellular parasites they are still considered to be extrinsic because they are secondary they are just acquired we can also have mechanical trauma mechanical trauma due to prosthetic heart valve so yung mga rbc mo tumatama dun sa prosthetic heart valve mo na sisira din po sila okay we also have thermal burns like your third degree burns bakit po third degree burns sir so remember that um during burns um there is increase uh there is increase um temperature and kapag increase yung temperature anong nangayari sa protein na did the nature sila and one thing that will also be denatured is your um hemoglobin and other protein components of your red blood cells and of course we also have your venoms that are found in your venomous um um venoms that are found in your um snakes and other reptiles and other animals na may venom okay so those are the extrinsic factor so to wrap it up lang no quickly your extrinsic defects can be divided into immune and non-immune defect kapag sinabi natin immune may kinalaman si immune system in the form of your antibodies pag sinabi natin non-immune wala siyang kinalaman sa immune system mo it's really just because of other external things like your coagulation infection mechanical um mechanical factors unlike your immune immune um immune defect talagang merong kinalaman yung immune system mo because it's your immune system that initiated the destruction of your rbc so hopefully today you you you've learned what intrinsic and extrinsic defects are so if you do have any questions i will be posting a discussion board on our tlc and at the same time i'll be sending you the copy of this video for you to be able to review this anytime anywhere hindi puto i want tv but thank you so much everyone for listening so this has been your sir joms and i if you have any questions i'll be opening the floor for your questions clarifications and any other concerns with regards to our topic for today again thank you so much and have a great day